title: Reactivation of the silenced BASP1 gene suppresses oncogenic WNT signaling in human colorectal cancer cells

city: Innsbruck

last: Hartl

state: Tyrol

address: Innrain 80-82

department: Institute of Biochemistry

institute: University of Innsbruck

summary: Starting from human colon cancer cells showing aberrant WNT/β-catenin/TCF4 signaling, hyperactivated MYC and silenced BASP1, we generated stable cell lines overexpressing BASP1, either ectopically, or by reactivating the dormant BASP1 promoter using a lentiviral CRISPR-based system. BASP1 encodes a neuronal signaling protein and transcriptional co-repressor, from which a tumor-suppressive function has been described in avian cell systems and in multiple human cancer cell types. Proteome and transcriptome analyses revealed activation of several tumor and metastasis suppressors in BASP1-expressing cells, which also show strong repression of the transformed phenotype in terms of contact inhibition, anchorage-independent growth, and tumorigenesis. Cells with reactivated BASP1 display a flat and differentiated morphology with enhanced migratory potential, accompanied by expression of multiple genes implicated in actin polymerization, focal adhesion, and neuronal migration. Furthermore, MYC protein expression is substantially repressed due to BASP1-mediated transcriptional MYC downregulation involving BASP1 interaction with β-catenin and binding to the MYC promoter. Upon BASP1 activation, multiple key proteins of the canonical WNT signaling pathway become suppressed. One of these BASP1 targets is the protein kinase TNIK catalyzing phosphorylation of TCF4, the latter required for transcriptional MYC activation. Results obtained with a preclinical TNIK inhibitor in human colorectal cancer cells show efficient abrogation of MYC expression and consequently impaired dimerization with its interaction partner MAX. The antagonistic BASP1 effect on MYC and the MYC dependency on TNIK could enhance the development of strategies to interfere with oncogenic functions of the cancer driver MYC.

overall_design: RNA-seq profiling of SW480 colon cancer cells and comparison with SW480 expressing ectopic BASP1 and SW480 with CRISPR-activated endogenous BASP1.

first: Weber

last: Leonie

first: Hartl

last: Markus


title: Genetic analysis of polyadenylation patterns reveals distinct classes of yeast genes and local chromatin effects on Pol II elongation

status: Public on Mar 02 2026

city: Boston

first: Zarmik

last: Moqtaderi

state: MA

address: 240 Longwood Avenue C2-355

department: BCMP

country: USA

institute: Harvard Medical School

summary: The poly(A) profile of a typical yeast gene comprises approximately 50 poly(A) sites corresponding to distinct 3’ mRNA isoforms.  Poly(A) profiles are shifted upstream in strains with slow RNA polymerase II (Pol II) elongation rates resulting from Pol II mutations or to depletion of histone chaperones FACT or Spt6.  Conversely, downstream-shifted poly(A) profiles occur in strains with fast Pol II elongation rates caused by Pol II mutations or by depletion of histones.  Downstream-shifted poly(A) profiles also arise when components of the cleavage/polyadenylation machinery are depleted.  Here we examine poly(A) profiles in 45 yeast strains with mutations that affect a wide variety of DNA- or RNA-based processes.  Typically, altered poly(A) profiles occur in only a subset of genes, and some strains show both upstream and downstream poly(A) shifts depending on the gene.  Hierarchical clustering of the poly(A) profiles reveals 6 classes of genes that behave similarly over the genetic conditions tested and have different RNA sequence preferences in their 3’ untranslated regions.  Many chromatin-modifying or chromatin-associated proteins affect poly(A) profiles, indicating that they affect the rate of transcriptional elongation.  Chromatin-modifying activities, but not cleavage/polyadenylation factors, often have non-uniform effects on 3’ mRNA isoform levels of the same gene, suggesting that chromatin differentially affects Pol II dwell time at individual sites during transcriptional elongation.

overall_design: 3' READS analysis of polyadenylated RNA samples to determine polyadenylation profiles of strains with deletions or anchor-away depletions affecting a variety of gene regulatory pathways.  The study involves two biological replicates for each strain and uses cells cultured to mid-log phase in YPD medium.

first: Joseph

middle: V

last: Geisberg

first: Kevin

last: Struhl


title: Molecular basis of target RNA cleavage by Cas13 I

city: Hong Kong

first: Joe

last: Lam

address: 21 Sassoon road

department: School of Biomedical Sciences

country: Hong Kong

institute: The University of Hong Kong

summary: RNA-targeting CRISPR-Cas13 enzymes are robust RNA knockdown tools with both on-target and collateral cleavage activities. However, to this date, the in vivo RNA cleavage mechanisms remain poorly understood. Here, we combine in vitro and in vivo methods to elucidate the exact cleavage sites of Cas13. We reveal that some subtypes of Cas13, including Cas13b and Cas13bt, cleave the target RNA in predominant positions, and rational engineering of Cas13 further improves the precision. Building on this fact, we developed RNA segment editing (RSE), a targeted RNA cleavage and repair method, to restore dysfunctional RNA in cells. We anticipate that RSE will enable precision RNA engineering for therapeutics and basic research.

overall_design: Cleavage preference analysis of different Cas13 proteins with a random substrate library

first: SC

last: Kwon


title: Reconstitution of human fetal ovaries reveals niche requirements for primordial germ cell-like cell progression

city: Leiden

first: Susana

last: Chuva de Sousa Lopes

address: Einthovenweg 20

department: Anatomy and Embryology

country: Netherlands

institute: Leiden University Medical Center

type: Expression profiling by high throughput sequencing

summary: Human primordial germ cell-like cells (hPGCLCs) can be specified from human induced pluripotent stem cells (hiPSCs), offering a valuable model for human germ cell development. However, further maturation steps of hPGCLCs rely on mouse feeders, or co-culture with mouse gonadal somatic cells. Exposure of hPGCLCs to human embryonic niche has not been attempted. Here, we co-cultured female hPGCLCs in two distinct somatic compartments. In reconstituted ovary (rOv) culture, human fetal germ cells proliferate and initiate meiosis, while hPGCLCs upregulate gonadal germ cell markers such as DDX4. Additionally, hPGCLCs can be supported in 3D culture by the amnion-like cells (AMLC) generated during PGCLC differentiation. Compared to rOV, hPGCLCs are less prone to dedifferentiation in PGCLC/AMLC aggregates. Finally, we demonstrated that SCF is crucial for the survival of hPGCLCs but not second trimester fetal germ cells. Together, this work highlights a shift in niche is required in human germ cell development.

overall_design: One hiPSC line was used for differentiation to hPGCLC and was used for single cell cluster analysis (Day 0, Day 5, Day 22)

middle: M

first: Ioannis

last: Moustakas

first: Arend

last: Overeem

first: Yolanda

middle: W

last: Chang


title: Adipocyte exosomal-derived microRNA30a-3p exacerbates liver steatosis in obese mice

city: Anshun

first: Longkun

last: Hu

state: Guizhou

address: Machang Town, Yunmanhu Campus of Guizhou Medical University

country: China

institute: Guizhou Medical University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Adipose tissue dysfunction results in hepatic lipid overload, driving the progression of liver steatosis and non-alcoholic steatohepatitis. The involvement of adipose tissue-derived small extracellular vesicles (sEVs) in initiating and propagating nonalcoholic fatty liver disease (NAFLD) remains unexplored. Herein, we unveiled that transplanting adipose tissue from high-fat diet (HFD)-fed mice exacerbated insulin resistance and liver steatosis in lean mice, and Sirt3 expression was markedly reduced in adipose tissue from both NAFLD patients and murine NAFLD models. Interestingly, fat-specific Sirt3 overexpression (Sirt3AKI) mice enhanced insulin sensitivity and improved liver steatosis under HFD feeding. Furthermore, adipose tissue-derived sEVs were found to regulate hepatic lipid metabolism in Sirt3AKI mice. In vitro studies demonstrated that Sirt3 overexpressing adipocytes (Sirt3OE) released sEVs to ameliorate lipid accumulation in palmitic acid/oleic acid (P/O)-stimulated hepatocytes. Conversely, sEVs derived from NAFLD patients exacerbated hepatic lipid accumulation in HFD-fed Sirt3AKI mice. MicroRNA sequencing further identified a significant decrease in miR-30a-3p levels in sEVs derived from Sirt3OE adipocytes. Fat-specific miR-30a-3p overexpression worsened hepatic steatosis in HFD-fed Sirt3AKI mice. In contrast, engineered sEVs loaded with miR-30a-3p antagonist or miR-30a-3p inhibition robustly enhanced insulin sensitivity and mitigated hepatic accumulation in HFD-fed mice. Mechanistically, CHIP-qPCR and CHIP-sequencing analyses revealed that Sirt3 suppressed miR-30a-3p transcription through H3K56 acetylation. Dual-luciferase reporter assays validated Beclin1 as a bona fide target mRNA of miR-30a-3p. Taken together, these findings highlight the critical role of exosomal microRNAs in mediating adipocyte-hepatocyte crosstalk, provide novel insights into the mechanisms underlying lipotoxicity in hepatocytes, and suggest miR-30a-3p inhibitor could be a therapeutic agent for NAFLD.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for Histone Acetyl H3K56  (H3K56ac) in 3T3-L1 cells.

first: Tian

last: Zhang

first: Diao

last: Chen

first: Yongxin

first: Fei

last: Zhou

first: Ruohan

last: lou

first: Yuxia


title: Multi-timescale analysis of whole-genome gene expression across the life cycle of wild Arabidopsis thaliana accessions in a natural environment

city: Seville

first: Francisco

middle: José

last: Romero-Campero

address: Americo Vespucio 49

department: Institute for Plant Biochemistry and Photosynthesis

country: Spain

institute: University of Sevilla

summary: Discerning the genes, regulatory networks, and environmental cues involved in plant development represents a major goal in the plant sciences. However, genes and regulatory networks have not evolved in controlled environmental conditions, which means that conducting experiments in natural settings is of paramount importance to dissect the underlying mechanisms of plant development realistically. We undertook common garden experiments in a natural environment to quantify whole-genome gene expression patterns over diurnal, seasonal, and annual timescales over the life-cycle phenology of the annual mustard Arabidopsis thaliana with wild Iberian accessions. Importantly, study accessions were locally adapted to their environments by adjusting key life-history traits across an altitudinal gradient in southern Spain. We found that diurnal (between morning and afternoon) and seasonal (across developmental stages) comparisons chiefly structured whole-genome gene expression in A. thaliana accessions. The most important difference between years, which differed in the precipitation regime, was in the number of over-represented genes detected across diurnal and seasonal timescales. Furthermore, we detected most of the differentially expressed genes from various biological functions as shared among all accessions. Nevertheless, the two accessions more similar in flowering time without an obligate flowering requirement also exhibited more similar gene expression patterns. Finally, we detected several flowering time genes from all known regulatory pathways across timescales, particularly from the photoperiod and circadian clock pathways. Overall, our results paved the way for more ambitious gene expression analyses in natural settings, whilst stressing the remarkable plasticity in both life-cycle phenology and gene expression in A. thaliana.

overall_design: RNA-seq profiling of different Arabidopsis thaliana ecotypes in a natural environment at different moments during the day and different developmental stages.

first: Picó

last: F. Xavier

first: Romero-Campero

last: Francisco J.


title: Chromatin Immunoprecipitation of GFP-HA-KERP2 expressing Entamoeba histolytica

city: Tokyo

first: Ruofan

last: Peng

state: Tokyo

address: 7-3-1 Hongo, Bunkyo-ku

department: International Health

country: Japan

institute: University of Tokyo

summary: Approximately 1 x 10^8 GFP-HA-KERP2 expressing Entamoeba histolytica cells were cross-linked in 0.5% formaldehyde (in PBS) for 10 minutes at room temperature. Cross-linking was quenched with 125 mM glycine for 5 minutes. Cells were washed once with PBS and subjected to nuclear fractionation using nuclei isolation buffer (10 mM Hepes-KOH pH 7.9, 1.5 mM MgCl2, 10 mM KCl, 2% NP-40, 1 uM E-64, 0.5 mM PMSF, and 1x cOmplete protease inhibitor cocktail). Nuclear pellets were resuspended in sonication buffer (50 mM Tris-HCl pH 8.0, 140 mM NaCl2, 1 mM EDTA, 1% Triton X-100, 0.1% sodium deoxycholate, 5 mM DTT, 1 uM E-64, 0.5 mM PMSF, 1x cOmplete) and sonicated using a Covaris instrument. Sonicated samples were centrifuged at 16000 x g for 20 minutes. A 200 uL aliquot of supernatant was transferred to a 1.5 mL Protein LoBind tube. Remaining sample was stored as input control. For immunoprecipitation, 1 mL of ChIP dilution buffer (16.7 mM Tris-HCl pH 8.0, 0.01% SDS, 1% Triton X-100, 1.2 mM EDTA, 167 mM NaCl, 0.5% BSA, 1x cOmplete) containing 50 uL of GFP(ab290)-antibody conjugated Dynabeads was added and rotated at 4 C for 12 hours. Beads were washed five times with low-salt wash buffer (20 mM Tris-HCl pH 8.0, 0.1% SDS, 1% Triton X-100, 2 mM EDTA, 150 mM NaCl), followed by two washes with high-salt wash buffer (same as above, but 500 mM NaCl). DNA-protein complexes were eluted with 200 uL of ChIP elution buffer (10 mM Tris-HCl pH 8.0, 1% SDS, 5 mM EDTA, 300 mM NaCl) at room temperature for 20 minutes. Input samples were thawed and diluted with 190 uL of elution buffer. All samples were incubated at 65 C for 8 hours to reverse cross-links, followed by RNase A treatment (1 uL) at 37 C for 1 hour and Proteinase K digestion (5 uL) at 55 C for 2 hours. DNA was purified by phenol/chloroform extraction with 1 uL glycogen as carrier, followed by ethanol precipitation overnight at -30 C. DNA pellets were washed with 80% ethanol, air-dried, and resuspended in 20 uL TE (ChIP) or 40 uL TE (input). DNA concentrations were quantified using a Qubit dsDNA High Sensitivity Assay Kit (Thermo Fisher Scientific). Purified DNA was submitted to Rhelixa for ChIP-seq.

overall_design: ChIP-seq of GFP-HA-KERP2 expressing E. histolytica pulled down by anti-GFP, together with input samples without antibody pull-down.

first: Herbert

middle: J

last: Santos

first: Tomoyoshi

last: Nozaki


title: Transcriptomic Analysis of Caco-2 Cells Co-cultured with KERP2-related Entamoeba histolytica Strains

summary: KERP2 is a secreted parasitic factor in Entamoeba histolytica that interacts with host colon epithelial cells, potentially contributing to pathogenesis. To investigate its influence on host gene expression, RNA-seq was performed on Caco-2 cells co-cultured with HA-KERP2-overexpressing E. histolytica (HA-KERP2), psAP-KERP2gs (partial KERP2 knockdown), or wild-type G3 strains, alongside untreated controls. Differential expression analysis identified upregulation of key pro-inflammatory mediators (IL1B, IL36G), signaling adapters (SLA), and heme-related genes (HRG) in HA-KERP2-treated cells, while cytoskeletal regulators (CYTIP, MYOCD), stress-response factor (NUPR1), and solute transporters (SLC15A3) were downregulated. In contrast, psAP-KERP2gs-treated cells exhibited increased expression of extracellular matrix components (TNC), contractility regulators (MYL7), and metabolic enzymes (CYP4B1), while genes involved in cilia function (CFAP43), solute transport (SLC2A12), and the pentose phosphate pathway (TKTL1) were downregulated.

overall_design: RNA-seq profiling of Caco-2 cells co-cultured with Entamoeba histolytica strains with differential KERP2 Expression


title: Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina [explant_CUT&Tag]

city: Bethesda

first: Matthew

last: Brooks

state: MD

address: 6 Center Dr Bldg 6, Rm 303

department: NEI

institute: NIH

summary: High aerobic glycolysis in retinal photoreceptors, as in cancer cells, is implicated in mitigating energy and metabolic demands. Lactate, a key product of glycolysis, is implicated in epigenetic regulation through histone lactylation in cancer. Here, we demonstrate that increased ATP production during retinal development is achieved primarily through augmented glycolysis. Histone lactylation, especially H3K18La, parallels enhanced glycolysis and its product, lactate, in developing retina and in retinal explants. Multi-omics analyses, combined with confocal imaging, reveal the localization of H3K18La near H3K27Ac in euchromatin at promoters of active retinal, especially photoreceptor, genes. H3K18La and gene expression also correspond to glucose metabolism in retinal explants. Evaluation of accessible chromatin at H3K18La promoters uncovers an enrichment of GC-rich motifs for transcription factors of SP, KMT and KLF families, among others, indicating specificity of H3K18La-mediated gene regulation. Our results highlight glycolysis/lactate/H3K18La as a regulatory axis in fine-tuning gene expression in developing and mature retina.

overall_design: Biologically replicated CUT&Tag assays for H3K18La and H3K27Ac were performed on retinal explant cultures. The dissected retinas were incubated in Neurobasal-A media supplemented with 5 mM glucose/25 mM glucose. Concensus peaks were determined and quantitative binding was performed. Gene-level differential expression analysis was performed using RNA-seq data.

first: Mohita

last: Gaur

first: Xulong

last: Liang

first: Milton

last: English

first: Laura

last: Campello

first: Claire

last: Marchal

first: Anand

last: Swaroop


title: RNA-seq Analysis of Entamoeba histolytica KERP2 Knockdown Strain

summary: This dataset contains RNA-seq data from Entamoeba histolytica strains, including a KERP2-knockdown strain (psAP-KERP2gs) and a control strain (psAP-mock). To investigate the functional role of KERP2 (EHI_065630), the knockdown strain was generated using small interfering RNAs with the psAP-2-Gunma plasmid. RNA-Seq analysis revealed distinct transcriptional profiles between KERP2gs and psAP-mock strains. GO and KEGG pathway enrichment analyses identified upregulation of genes involved in proteolysis regulation, sulfur amino acid metabolism, and amoebiasis in the KERP2-knockdown strain. Notably, cysteine synthases (EHI_024230, EHI_160930), methionine γ-lyase (EHI_057550), cysteine protease (EHI_010850), and pore-forming peptides (EHI_169350, EHI_194540, EHI_15940) were significantly upregulated. These findings suggest a potential role for KERP2 in regulating parasitic activities, possibly through chromatin binding. This dataset provides a valuable resource for studying KERP2-associated gene expression changes in E. histolytica.

overall_design: RNA-seq profiling of KERP2 knockdown strain and the control psAP-mock strain.


title: Genomic Analysis of T cell Receptors Provides Novel Insights of Cancer Immunology in Lynch Syndrome Carriers

city: Houston

first: Eduardo

last: Vilar-Sanchez

state: TX

address: 1515 Holcombe Blvd

institute: The University of Texas MD Anderson Cancer Center

summary: Lynch Syndrome (LS) provides the perfect context to understand DNA mismatch repair deficient (MMRd) carcinogenesis. LS carriers develop MMRd tumors with high neoantigen loads, which are shared by different LS tumors and recognized by T-cell receptors (TCRs) to trigger adaptive immunity.  However, the TCR landscape in LS remains unexplored. Therefore, we performed TCR-sequencing in 277 blood samples from 102 LS cancer survivors, 130 LS previvors, and 45 controls, as well as three LS colorectal cancers, and 11 pre-cancers. For the first time, we found that up to 41% of the most expanded TCRβs from colorectal cancers and pre-cancers are detectable in the blood of several LS carriers, whereas these TCRs have minimal or no expansion in the blood of controls. Additionally, we developed a classification model that distinguishes LS carriers from controls with excellent performance using a set of 1,114 TCRβs that associates with all LS carriers, regardless of MMRd cancer history, and a set of 2231TCRβs that associates with LS previvors who have never developed cancer. This study is the first to describe circulating TCRβs that recognize neoantigens derived from colorectal cancers and pre-cancers in LS carriers, moving the field towards the identification of a blood based TCRβ cancer biomarker.

overall_design: We used this RNF43_3 peptide in conjunction with a dextramer to stimulate PBMCs from a LS patient, thereby obtaining RNF43-specific CD3+ T-cells. Subsequently, we performed single-cell RNA and single-cell TCR sequencing on these RNF43-dextramer-specific CD3+ T-cells. We then compared the TCRβ sequences obtained from these cells to our Lynch-associated signature TCRβs and separately to our LS-survivor-associated signature TCRβs to assess overlap and validate the neoAg specificity of the identified TCRβ signature sequences.


title: Molecular biological effect of Rbm20 I538T knock-in mice on skeletal muscle

city: Nishinomiya

first: Takuma

last: Yamamoto

address: 1-1 Mukogawa-Cho

institute: Hyogo Medical University

summary:
Introduction: RBM20 regulates pre-mRNA splicing, and its mutations cause dilated cardiomyopathy by disrupting cardiac RNA splicing, particularly of the TTN gene. While RBM20 is known to affect TTN splicing in the heart, its role in skeletal muscle remains unclear. This study investigated the effects of an RBM20 variant using an Rbm20 I538T knock-in mouse model, performing pathological and RNA-seq analyses to assess its impact on skeletal muscle.

Methods: We used Rbm20 I538T knock-in mouse and performed pathological and RNA-seq analyses to evaluate the effect of the variant on skeletal muscle.

Results and discussion: Histopathological examination revealed no skeletal muscle abnormalities in any genotype. Although potential splicing effects on Ttn and Ldb3 were considered, no abnormal splicing was detected. Differentially expressed gene analysis showed no differences among genotypes. Therefore, we conclude that the Rbm20 I538T variant does not affect the splicing of skeletal structural proteins or lead to a skeletal muscle phenotype.

overall_design: Using the CRISPR/Cas system, we generated KI mice harboring the c.T1613C (p.I538T) point mutation in the mouse Rbm20 gene, which corresponded to human c.T1607C (p.I536T).


title: Transcriptional programs associated with migratory capacity and 5-ALA–induced PpIX fluorescence in glioblastoma

status: Public on Mar 01 2026

city: Bunkyo-ku

first: Kouichi

last: Tabu

address: 1-5-45, Yushima

institute: Institute of Science Tokyo

summary:
Glioblastoma (GBM) cells were fractionated by a two-dimensional Transwell migration assay (no extracellular matrix coating) into migratory and non-migratory populations, followed by subdivision based on 5-aminolevulinic acid (5-ALA)–induced protoporphyrin IX (PpIX) fluorescence (high vs low).
Gene expression profiling was performed using Agilent one-color microarrays. One biological sample per condition was analyzed (no biological replicates).

overall_design: A patient-derived GBM line was subjected to chemotactic migration-based fractionation using a non-coated Transwell assay to separate migratory and non-migratory fractions. Each fraction was further separated into PpIX-high and PpIX-low populations after 5-ALA exposure, yielding four conditions (Non-migratory/PpIX-low, Non-migratory/PpIX-high, Migratory/PpIX-low, Migratory/PpIX-high). Total RNA from each condition was analyzed on an Agilent one-color microarray platform (Agilent-072363). Processed data represent normalized signal intensities used for downstream transcriptomic analyses.


title: Temperature and developmental stage govern intestinal susceptibility to human coronavirus 229E.

city: Wrocław

first: Heng-Chang

last: Chen

address: Stablowicka 147

country: Poland

institute: Łukasiewicz Research Network – PORT Polish Center for Technology Development

summary: Transcriptional profiling of fetal, pediatric, and adult human intestinal enteroids following Human Coronavirus 229E infection at 32C and 37C.

overall_design: 6 different human intestinal enteroids (2 fetal donors, 2 pediatric donors, and 2 adult donors) were generated, differentiated, and subsequently infected for 48h with clinical strain of  human coronavirus 229E at either 32C or 37C. Controls included mock-infected enteroids.

first: Aleksandra

last: Synowiec

first: Katarzyna

last: Owczarek

first: Maciej

last: Borowiec

first: Michal

last: Pietrusinski

first: Izabela

last: Drozdz

first: Agnieszka

last: Robaszkiewicz

first: Krzysztof

last: Pyrc


title: Metformin-induced longevity is associated with retrotransposon dynamics in yeast chronological aging

city: Irapuato

first: Jimena

middle: Meneses

last: Plascencia

state: Guanajuato

address: Libramiento Norte Km 9.6, 36821 Irapuato, Gto.

department: UGA-LANGEBIO

country: Mexico

institute: CINVESTAV

summary: The widely used antidiabetic drug metformin extends lifespan across diverse model organisms,  from yeast to primates. However, the cellular mechanisms underlying its anti-aging effects remain only partially understood. Here, we combined large-scale genetic screening and high-resolution  lifespan phenotyping with transcriptomic and proteomic analyses to provide a systems view of  metformin’s impact on the chronological lifespan of Saccharomyces cerevisiae. Unexpectedly, we  uncovered pronounced gene-drug interactions between metformin and chromatin-modifying factors. Specifically, deletions of Set3C histone deacetylation complex subunits phenocopied the longevity effect of metformin, with no additive benefit when combined, suggesting convergence 10 on shared pathways. Transcriptome profiling further revealed that metformin reprogrammed stationary-phase gene expression, with Ty1-copia retrotransposons emerging as a consistently induced signature, thereby suggesting a possible mechanism for the observed interactions with Set3C regulation.

overall_design: We performed RNAseq analysis comparing populations of WT cells in mid exponential and late stationary phase with or without metformin.

first: Meneses-Plascencia

last: Jimena

first: Moreno-Méndez

last: Ericka

first: DeLuna

last: Alexander


title: CD47 activates ROBO2 signaling to regulate glioblastoma cell plasticity and metabolism

status: Public on Mar 09 2026

city: Adelaide

first: John

last: Toubia

address: Frome Rd

country: Australia

institute: Centre for Cancer Biology

summary: CD47 inhibits phagocytosis by myeloid cells, contributing to immune evasion by cancer cells. Although CD47-blocking antibodies have shown promise in treating various malignancies, their efficacy in glioblastoma (GBM) remains limited, and the role of CD47 beyond immune escape is poorly understood. Here, we show that CD47 is highly expressed at the invasive edge of GBM tumours, with elevated expression correlating with poorer patient survival. We demonstrate that CD47 loss reduces proliferation, migration, and invasion, independently of immune activity leading to decreased GBM tumour burden and prolonged survival in vivo. Mechanistically, our study reveals that CD47 regulates ROBO2 signaling and enhances mitochondrial respiration. Furthermore, we demonstrate that combined loss of CD47 or ROBO2 with inhibition of mitochondrial function significantly increases GBM cell death. These findings highlight CD47 as a key regulator of GBM cell and metabolic plasticity, offering a novel therapeutic strategy by targeting CD47 or ROBO2 in combination with mitochondrial inhibitors.

overall_design:
To investigate the role of CD47 in regulating GBM cell plasticity, we knocked out CD47 in U-87MG GBM cells using CRISPR/Cas9 technology.
We then performed gene expression profiling analysis using RNA-seq data from wild-type (WT) and CD47-CRISPR-Knockout (KO) cells, with three biological replicates per group.
Comparative transcriptomic analysis between the WT and CD47 KO groups was performed to identify differentially expressed genes and pathways regulated by CD47.

first: Ruhi

last: Polara

first: Nirmal

last: Robinson


title: BCL6B suppresses acute myeloid leukemia progression by transcriptionally repressing GGT5 and modulating MAPK signaling

city: Kunming,Yunnan,CHina

first: Pan

last: Yuqing

address: 295 Xichang Road, Wuhua District, Kunming City, Yunnan Province, China

institute: the First Affiliated Hospital of Kunming Medical University

summary: Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy with poor prognosis. In this study, we investigated the role of B-cell lymphoma 6 member B (BCL6B) in AML progression. Integrated analyses of TCGA-LAML, GTEx, and GEO datasets revealed that BCL6B was significantly downregulated in AML and associated with adverse clinical features and shorter overall survival. Functional assays demonstrated that BCL6B overexpression suppressed AML cell proliferation, induced apoptosis, and caused G0/G1 cell cycle arrest, whereas BCL6B knockdown exerted opposite effects. Mechanistically, transcriptome analysis and promoter-binding assays identified gamma-glutamyltransferase 5 (GGT5) as a direct transcriptional target of BCL6B. BCL6B bound to the GGT5 promoter and repressed its expression, thereby modulating MAPK signaling by inhibiting ERK phosphorylation and activating p38 and JNK pathways. Rescue experiments confirmed that GGT5 partially mediated the biological effects of BCL6B. In vivo, BCL6B overexpression significantly inhibited leukemic growth, migration, angiogenesis, and improved survival in zebrafish and mouse xenograft models. These findings identify the BCL6B–GGT5–MAPK axis as a key regulatory pathway in AML and a potential therapeutic target.

overall_design: This study employed an integrated experimental framework combining bioinformatics, in vitro functional assays, and in vivo validation. Public transcriptomic datasets (TCGA-LAML, GTEx, GEO) were analyzed to evaluate BCL6B and GGT5 expression patterns, clinical associations, and prognostic relevance. Clinical bone marrow samples from AML patients and healthy donors were used for expression validation by RT-qPCR. Gain- and loss-of-function experiments were performed in multiple AML cell lines using lentiviral-mediated BCL6B overexpression or shRNA knockdown. Cell proliferation, apoptosis, and cell cycle distribution were assessed by CCK-8 assays and flow cytometry. Epigenetic regulation of BCL6B was examined using methylation-specific PCR and decitabine treatment. RNA sequencing was conducted to identify BCL6B-regulated genes, followed by GO and KEGG pathway enrichment analyses. Direct transcriptional regulation of GGT5 by BCL6B was validated using dual-luciferase reporter assays and electrophoretic mobility shift assays. MAPK pathway activation was analyzed by Western blotting. Functional rescue experiments were performed by co-overexpression of GGT5 and BCL6B. In vivo effects were evaluated using zebrafish and nude mouse xenograft models to assess tumor growth, migration, angiogenesis, and survival.

first: Yuqing

last: Pan

first: Kun

last: Wu

first: Chong

last: Guo

first: Yixun

last: Li

first: Zhengjie

last: Zhao

first: Shenju

last: Cheng

first: Yan

last: Du


title: Serotonin transporter downregulation is associated with aortic stenosis, and early profibrotic remodeling is mitigated by pharmacological inhibition of HTR2B receptor

city: Philadelphia

first: Ting

last: Peng

state: PA

address: CTRB 6200

department: Pathology and Laboratory Medicine

institute: Children's hospital of Philadelphia

summary:
Background: Aortic Stenosis (AS) is a highly prevalent disease involving physiological and structural remodeling of aortic valve, yet lacks effective medical therapy to halt its progression. Serotonin (5HT) signaling has been implicated in valvular disease. We hypothesized that AS is associated with impaired 5HT clearance due to reduced serotonin receptor (SERT) expression and increased 5HT receptor (HTR) activity.
Methods: Sixty-six patients with severe AS undergoing aortic valve (AV) replacement were enrolled in the study, and samples from their explanted AV were harvested. Anatomically normal control AVs were obtained from transplant donors. Explanted AVs were collected for gene expression analysis and 5-HTTLPR genotyping. Gene expression was assessed by RT2-profiler gene array. In vivo, 8-week-old mice received 28-day Angiotensin-II (AngII) infusions ± HTR2B antagonist (LY272015) through subcutaneous Alzet osmotic-pump implants. AV structure and function were assessed via echocardiography, histology, and RNA sequencing. Human aortic valve interstitial cells (AVICs) were treated with either H2O2 or AngII ± SERT siRNAs to assess 5HT signaling and fibrotic/osteogenic markers.
Results: AS patients exhibited reduced SERT and increased HTR expression. Oxidative stress in cultured human AVICs suppressed SERT and induced HTR2B expression. AngII ± SERT siRNA promoted VIC osteogenic marker expression. In mice, AngII caused AV thickening, increased velocities and gradients, and activation of fibrosis and calcification-related gene sets, including serotonin, TGFβ, Wnt/β-catenin, PI3K/Akt, and Notch pathways. Pharmacological inhibition of HTR2B preserved AV structure, normalized transvalvular velocities and pressure gradients, and reversed AngII-induced transcriptional changes.
Conclusions: In human and mouse AVs, reduced SERT and elevated HTR2B signaling contribute to early-onset fibro-calcific remodeling. HTR2B inhibition by LY272015 reverses these effects, suggesting it as a potential therapeutic strategy for AS.

overall_design: 8-week-old wild type male mice, Jackson Lab, (C57BL/6J) were fed a hypercholesterolemic diet (Breslow Western Diet, Fisher and Son Inc. Cat#: TD1810724) and infused with AngII (1000 ng/kg/min) using osmotic pumps (Alzet 2004) for 28 days, as previously described. Osmotic pumps were implanted subcutaneously on the back, posterior to scapulae, through a small skin incision. LY272015 treatment (3 mg/kg in sterile PBS) was given twice/week over the 28-day AngII infusion by intraperitoneal injection, as previously described. After 28 days, mice in the AngII and AngII + LY groups had their pumps removed and survived for an additional 48 hours. They were then anesthetized with isoflurane, followed by heart perfusion with PBS and sample collection. Hearts were collected and aortic valves were extracted under dissection microscope. RNA was extracted and purified for bulk RNAseq experiment. Group sizes were 4 mice per group (Control, LY272015, AngII, and AngII+LY).

first: Dov

last: Levine

first: Chiara

last: Camillo

first: Estibaliz

last: Castillero

first: Emre

last: Bektik

first: Yaagnik

last: Kosuri

first: Anthony

last: Campbell

first: Cary

last: Karcher

first: Abba

last: Krieger

first: Liming

last: Pei

first: Nicole

last: Zeak

first: Erfan

last: Faridmoayer

first: Mark

last: Oyama

first: Juan

middle: B

last: Grau

first: Robert

last: Levy

first: Giovanni

last: Ferrari


title: Spatial transcriptomic profiling of human heart tissue obtained from mRNA vaccine-associated myocarditis cases using GeoMx DSP

city: Tsukuba

first: Atsushi

last: Kawaguchi

address: 1-1-1 Tennodai

institute: University of Tsukuba

summary: Spatial transcriptomic analysis was performed using the NanoString GeoMx Digital Spatial Profiler to characterize region-specific gene expression patterns in heart tissue sample obtained from mRNA vaccine-associated myocarditis cases.

overall_design: Spatial transcriptome profiling was performed to compare gene expression patterns in myocardial regions between mRNA vaccine-associated myocarditis cases and control samples.


title: H3K27me3 spreading organizes canonical PRC1 chromatin architecture to regulate developmental programs

city: Montreal

first: Jacek

last: Majewski

state: Quebec

address: 740 Dr. Penfield

department: Human Genetics

country: Canada

institute: McGill University

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Plasma proteomics improves thrombosis prediction in patients with cancer and identifies targetable IL-17–driven endothelial activation

city: Boston

first: Marisa

last: Brake

address: 3 Blackfan Cir

institute: Beth Israel Deaconess Medical Center

summary: Thrombosis remains a major cause of morbidity and mortality in cancer patients. Existing risk models fail to reliably predict venous thromboembolism (VTE), underscoring the need for more accurate predictive models. In this study, we conducted a high-throughput proteomic analysis of 1,105 plasma proteins from newly diagnosed lung and gastric cancer patients prospectively monitored for VTE development. Utilizing a Bayesian probabilistic machine learning approach, we developed a predictive model incorporating 11 protein biomarkers and five clinical parameters (age, sex, history of VTE, body mass index, and hemoglobin), which significantly outperformed the Khorana prediction model. Orthogonal validation in an external placebo cohort from a phase III trial confirmed the model’s predictive power. Further investigation into the mechanistic role of CD200R1, a checkpoint receptor limiting leukocyte inflammatory response that contributed strongly to the model, showed that reduced levels in plasma correlated with higher D-dimer and thrombosis risk. In CD200R1-deficient mice, elevated thrombin-antithrombin complexes confirmed a prothrombotic state characterized by increased IL-17A and endothelial inflammation. Administration of anti-IL-17A antibodies to CD200R1 deficient mice normalized thrombin generation in vivo, and a meta-analysis of human clinical IL-17A inhibitory antibody studies confirmed antithrombotic activity. These findings improve the prediction of thrombosis in cancer and highlight the utility of plasma proteomics to identify unanticipated mechanistic insights and therapeutic targets in thrombo-inflammatory disease.

overall_design: To investigate transcriptional difference in gene expression in whole liver between wildtype and Cd200r1 knockout mice.

first: Brake

last: Marisa

first: Schulman

last: Sol

first: Zwicker

last: Jeff


title: Transcriptomic Analysis of WT and IGF2BP2 KO Macrophages Reveals Metabolic Alterations

city: Saarbruecken

first: Jessica

last: Hoppstaedter

address: Campus C2 3

department: Pharmacy

country: Germany

institute: Saarland University

summary:
This dataset contains RNA-Seq data from wild-type (WT) and IGF2BP2 knockout (KO) bone marrow-derived macrophages (BMMs) under basal and IL-4-stimulated conditions. Loss of IGF2BP2 led to significant transcriptional changes, particularly in genes regulating metabolism, mitochondrial function, and cell migration. Pathway analysis revealed a metabolic shift toward glycolysis and reduced migratory capacity.
Details: Int J Biol Sci 2026; 22(6):2754-2773. doi:10.7150/ijbs.122142

overall_design: Myeloid-specific IGF2BP2 KO mice were generated by crossing B6.Cg-Igf2bp2tm1.1Thor/J mice (The Jackson Laboratory), which carry loxP sites flanking exons 4 and 5 of the Igf2bp2 gene, with 29P2-Lyz2tm1(cre)Ifo/J mice (The Jackson Laboratory). Control wild-type (WT) mice were littermates that did not carry floxed alleles and either expressed or lacked Cre recombinase. Bone marrow-derived macrophages (BMMs) were isolated from WT and IGF2BP2 KO mice and differentiated with M-CSF for six days. Cells were either left untreated (M0) or stimulated with IL-4 (20 ng/mL) for 8 hours to induce M2 polarization. RNA was extracted, and libraries were prepared using poly(A)-enriched mRNA. Sequencing was performed on an Illumina NextSeq 500 platform.

first: Hanna

middle: S

last: Schymik

first: Gilles

last: Gasparoni

first: Jörn

last: Walter

last: Hoppstädter

first: Alexandra

middle: K

last: Kiemer


title: Arabidopsis thaliana accumulates DHEA after infection with phytopathogenic fungi - effects on plants and fungi

city: Jena

first: Emanuel

last: Barth

address: Leutragraben 1

department: Bioinformatics Core Facility FSU Jena

institute: Friedrich Schiller University Jena

summary: Progestogens and androgens have been found in many plants, but their physiological functions remain unclear. We here show that the dehydroepiandrosterone, a C19-steroid, accumulates during infection of A. thaliana with the pathogenic fungus A. brassicicola. Moreover, dehydroepiandrosterone inhibits growth of the A. brassicicola in an ergosterol-independent way. We hypothesize that this is caused by an infection-adapted metabolism of A. thaliana as part of stress-response.

overall_design:
Dehydroepiandrosterone was applied exogenously to analyze the effects of this androgen on development and gene expression of Arabidopsis thaliana. Moreover, we analyzed growth, sterol pattern and membrane-integrity of Alternaria brassicicola confronted with dehydroepiandrosterone.
Comparative gene expression profiling analysis using data obtained from RNA-seq of A. thaliana leaves under three different conditions.

first: Ceren

last: Oktay

first: Glendis

last: Shiko

first: Maximilian

last: Liebl

first: Felix

last: Feiste

first: Sarah

last: Mußbach

first: Karl

middle: L

last: Körber

first: Michael

last: Reichelt

first: Kilian

last: Ossetek

first: Christoph

last: Müller

middle: C

last: Furch

first: Jan

last: Klein


title: Targeting TRIM24 promotes neuroblastoma differentiation and decreases tumorigenicity via LSD1/CoREST complex

city: Shanghai

first: Haizhong

last: Feng

state: Shanghai

address: Pujian Road 160

department: Ren Ji Hospital

institute: Shanghai Jiao Tong University

summary: High-risk neuroblastoma (NB) still has an unfavorable prognosis and inducing NB differentiation is a potential strategy for clinical treatment, yet underlying mechanisms are still elusive. Here we identify TRIM24 as an important regulator of NB differentiation. Trim24 was highly expressed in spontaneous NB in TH-MYCN transgenic mice and clinical NB specimens. And it was associated with poor NB differentiation and functioned as an unfavorable prognostic factor. Knockout of TRIM24 in MYCN-amplified neuroblastoma cells promoted cell differentiation and reduced cell stemness, cell colony formation in soft agar and subcutaneous xenograft tumor growth in nude mice. Mechanistic investigations demonstrated that TRIM24 knockout activated retinoic acid pathway and suppressed LSD1/CoREST complex formation and inhibited the transcription of genes involved in NB differentiation such as ZIC4. Targeting TRIM24 in combination with retinoic acid (RA) synergistically promoted NB cell differentiation and inhibited cell viability. Taken together, Our findings demonstrate that TRIM24 is critical for NB differentiation and suggest that TRIM24 is a promising therapeutic target in combination with RA in NB differentiation therapy.

overall_design: Gene expression profiling of in vitro control and TRIM24 knockout CHP-134 cells (in biological replicates).


title: Critical role of Cathepsin L/V in regulating endothelial cell senescence

city: changsha

first: Chan

last: Li

state: Hunan

address: No 87 Xiangya road, Changsha, Hunan, China.

institute: Xiangya Hospital, Central South University

summary: To explore the role of Cathepsin L/V in regulating endothelial endothelial cell senescence.

overall_design: 400μM H2O2 was used to induce cellular senescence and adenovirus was applied to enhance the expression of CTSV in HUVECs.RNA-sequencng analysis was conducted to compare gene expressons in different groups

first: Zhaoya

last: Liu

first: Ruizheng

last: Shi

first: Hua

last: Zhong


title: Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion

status: Public on Feb 28 2026

city: Pittsburgh

first: Xiaoming

last: Hu

address: 200 lothrop street

department: Neurology

institute: University of Pittsburgh

summary: We employed single-cell RNA sequencing to map cell populations and explore vascular responses in mouse brains collected 42 days after asymmetric common carotid artery stenosis (ACAS)-induced chronic cerebral hypoperfusion

overall_design: Brain hemispheres were collected from the ameroid constrictor side at 42 days after ACAS. Single cells were prepared and subjected to scRNAseq

first: Jun

last: Chen


title: Ethylene Signaling Enhances Mitochondrial Stress Tolerance Independently of the Transcription factor ANAC017 in Arabidopsis

city: Madrid

first: Yovanny

last: Izquierdo

state: Madrid

address: Calle Darwin, 3

department: Plant Molecular Genetics

institute: CNB-CSIC

summary: Mitochondria are central to plant metabolism, yet the diversity of mechanisms plants use to cope with mitochondrial stress and its implications in cellular signaling are not fully understood. In this study, we analyzed Arabidopsis noxy (nonresponding to oxylipins) mutants affected in 9-HOT (9(S)-hydroxy-10,12,15-octadecatrienoic acid) signaling, mitochondrial function and ethylene (ET) signaling to dissect plant responses to a range of mitochondrial stresses, including inhibitors of all electron transport chain complexes and mitochondrial translation. All noxy mutants showed resistance to antimycin A (AA), implicating Complex III and 9-HOT signaling in mitochondrial stress adaptation. Notably, noxy22/eto1-14, an ET overproducer mutant, displayed resistance to all tested inhibitors independently of the canonical mitochondrial retrograde pathway mediated by ANAC017. We found similar results in eto1-5 and eto1-13 alleles, thus sustaining a role for ET in mitochondrial protection. Histochemical and RNA-seq analysis revealed that AA induced ANAC017-regulated genes early and independently of ET signaling whereas EIN2 contributed in later induction of AA-associated immune responses. EIN2 was required for full activation of AA-induced resistance against the biotrophic pathogen Hyaloperonospora arabidopsidis, but not against the necrotroph Plectosphaerella cucumerina. Collectively, our findings point to a complex network that coordinates distinct but overlapping responses to mitochondrial dysfunction and integrates them into broader stress pathways.

overall_design: RNA-seq profiling of 12-day-old wild type (Col0) and ein2-5 plants in response to 20 µM AA 3 h and 24 h after treatment. MS-treated and untreated plants were used as controls.

first: Bran

last: López

first: Tomás

last: Cascón

first: Carmen

last: Castresana


title: Unraveling Diabetic Cardiomyopathy (DCM): The Critical Role of the Yap–miR-22-3p–Sirt1 axis in the Pathogenesis of DCM

city: Guangzhou

first: Ning

last: Hou

address: Xinzao Street

institute: Guangzhou Medical University

summary:
Background: Diabetic cardiomyopathy (DCM), characterized by myocardial hypertrophy and myocardial fibrosis, is a severe complication of diabetes. Yes-associated protein (Yap) activation contributes to myocardial remodeling and cardiac dysfunction. This study investigated the role of Yap and its molecular mechanism in DCM.
Methods: Yap expression was assessed in mice with type 2 diabetes mellitus (T2DM) and high glucose (HG) + insulin-treated neonatal rat cardiomyocytes (NRCMs). Adeno-associated virus transfection, siRNA transfection, and a transgenic mouse model were used to manipulate Yap and sirtuin 1 (Sirt1) expression in vivo and in vitro. RNA sequencing, differential gene analysis, and miRNA sequencing were used to identify downstream targets of Yap and the underlying mechanisms. Functional assays were used to evaluate cardiomyocyte hypertrophy and fibrosis through molecular markers, cell morphology, and echocardiography.
Results: Yap expression was increased in HG + insulin-treated NRCMs and in the hearts of mice with T2DM, thereby promoting myocardial hypertrophy and fibrosis. Yap inhibition reduced the cardiomyocyte cross-sectional area, collagen deposition, and the levels of the hypertrophy markers atrial natriuretic peptide and β-myosin heavy chain. RNA sequencing identified Sirt1 as a downstream target of Yap. Bioinformatic analysis suggested that Yap positively regulates miR-22-3p, which inhibits Sirt1. Yap inhibition increased Sirt1 expression, mitigating myocardial remodeling. Conversely, Sirt1 knockdown reversed the protective effects of Yap inhibition, restoring hypertrophy and fibrosis.
Conclusion: Yap promotes DCM progression by increasing miR-22-3p expression and suppressing Sirt1 expression. Targeting the Yap–miR-22-3p–Sirt1 axis might represent a novel therapeutic strategy for DCM, thereby improving myocardial structure and function.

overall_design: Primary neonatal rat cardiomyocytes (NRCMs) were isolated from 1–2-day-old neonatal SD rats. In brief, hearts collected from anesthetized neonatal rats were digested with pancreatic enzymes and type II collagenase.To create an in vitro diabetic model, NRCMs were initially cultured in DMEM supplemented with 1% FBS and 1 g/L glucose for 14 h, followed by 48 h of treatment with 33 mM glucose and 100 nM insulin. Yap expression in these cells was manipulated using adenovirus. The cells were categorized into the Ad-Yap shRNA or Ad-Yap WT group under high glucose conditions. The group transfected with Ad-GFP with or without glucose + insulin treatment served as the CON group. Total RNA was extracted from NRCMs using a Trizol reagent kit. We then performed gene expression profiling analysis using data obtained from RNA-seq of adenovirus infected cardiomyocytes. Comparative gene expression profilling analysis of RNA-Seq data for infected cells.

first: Yilang

first: Yuling

last: Lian


title: Effects of phytogalactolipids on drug-resistant colorectal cancer

city: Taipei City

first: Yu-Ling

last: Lin

address: No. 128, Sec. 2, Academia Road, Nankang, Taipei, Taiwan 115

department: Agricultural Biotechnology Research Center (ABRC)

country: Taiwan

institute: Academia Sinica

summary: Drug resistance is one of the major challenges in colorectal cancer (CRC) treatment. Overcoming drug resistance and improving the treatment effect of CRC patients who have developed drug resistance is a crucial issue. Crassocephalum rabens and Bidens pilosa are edible plants that are also commonly used as a folk medicine. This study explored the pharmacological mechanism and therapeutic efficacy of bioactive compounds isolated from Crassocephalum rabens and Bidens pilosa for treating drug-resistant CRC in vitro and in vivo.

overall_design: The transcriptional profile of wild-type HT-29 cells was analyzed by RNA-seq following 24h exposure to CRA or BP.

first: Ting-Yan

last: Jian

first: Han-Huei


title: Autism-like phenotypes and increased NMDAR2D expression in mice with KDM5B histone lysine demethylase deficiency

status: Public on Feb 26 2026

city: Exeter

first: Michiel

middle: Albert

last: Basson

address: Hatherly Labs, Prince of Wales Road

country: United Kingdom

institute: University of Exeter

summary: Loss-of-function mutations in genes encoding lysine methyltransferases (KMTs) and demethylases (KDMs) specific for trimethylated of lysine 4 of histone 3 (H3K4me3) are associated with neurodevelopmental conditions, including autism spectrum disorder and intellectual disability. To study the role of KDM5B (Lysine DeMethylase-5B)-mediated H3K4me3 demethylation, we investigated neurodevelopmental phenotypes in mice without KDM5B demethylase activity. These mice exhibited autism-like behaviours and increased brain size. H3K4me3 levels and the expression of neurodevelopmental genes were increased in the developing Kdm5b mutant neocortex. These included elevated expression of Grin2d. The Grin2d gene product NMDAR2D was increased in synaptosomes isolated from the Kdm5b-deficient neocortex and treating mice with the NMDAR antagonist memantine rescued deficits in ultrasonic vocalisations and reduced repetitive digging behaviours. These findings suggest that increased H3K4me3 levels and associated Grin2d gene upregulation disrupt brain development and function, leading to socio-communication deficits and repetitive behaviours, and identify a potential therapeutic target for neurodevelopmental disorders associated with KDM5B deficiency.

overall_design: Single nuclei RNA sequencing was performed on neocortices from wild-type and Kdm5b deltaARID/deltaARID mice at postnatal day 5. Nuclei were isolated and samples were processed with Parse Biosciences Evercode WT kit (chemical v3).

first: Leticia

last: Pérez-Sisqués

first: Shail

middle: U

last: Bhatt

first: Angela

last: Caruso

first: Josephine

last: Robb

first: Alex

middle: P

last: Donovan

first: Rosemary

middle: A

last: Bamford

first: Alejo

last: Torres-Cano

first: Shoshana

last: Spring

first: Eleanor

last: Hendy

first: Talia

middle: E

last: Gileadi

first: Martyna

last: Panasiuk

first: Jed

last: Trengove

first: Neeru

last: Jindal

first: Mohi

last: Ahmed

first: Joyce

last: Taylor-Papadimitriou

first: Diana

last: Cash

first: Nicholas

last: Clifton

first: Jacob

last: Ellegood

first: Laura

last: Andreae

first: Jason

last: Lerch

first: Maria Luisa

last: Scattoni

first: K

last: Giese

first: Cathy

last: Fernandes

first: M


title: UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through GATA2-ST6GALNAC5 and PRC2 interactions

city: Irvine

first: Claudia

last: Benavente

state: CA

address: 839 Health Sciences Road, Sprague Hall B200

institute: University of California, Irvine

summary: Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma characterized by early metastasis, immune evasion, and limited therapeutic progress. While its genomic landscape is well defined, the epigenetic programs sustaining its lineage fidelity, metastatic potential, and immune evasion remain incompletely understood. We used inducible CRISPR-Cas9 knockout models, transcriptomic and epigenetic profiling, immune-competent allografts, and genetically engineered mouse models (GEMMs) to investigate the role of the chromatin regulator UHRF1 in SCLC progression. We identify the chromatin remodeler UHRF1 as a subtype-independent oncogenic driver in SCLC, with high expression correlating with poor survival. UHRF1 loss impaired proliferation, invasion, and metastasis across ASCL1-, NEUROD1-, and POU2F3-driven subtypes. Mechanistically, UHRF1 maintained neuroendocrine lineage identity and suppressed immune gene expression via DNA methylation and interaction with PRC2. UHRF1-deficient tumors displayed increased infiltration of CD8⁺ T cells, monocytes, neutrophils, and dendritic cells, along with a higher CD8⁺/Treg ratio. Secretome profiling revealed upregulation of chemokines, linking UHRF1 loss to active recruitment of immune effector cells. In parallel, UHRF1 regulated the pro-metastatic sialyltransferase ST6GALNAC5 via the transcription factor GATA2. UHRF1 loss downregulated GATA2 and ST6GALNAC5, impairing tumor dissemination. Lastly, UHRF1 depletion increased expression of cancer/testis antigens such as MAGE-A4, without altering DLL3 levels, suggesting compatibility with both antigen-specific and DLL3-targeted immunotherapies. In conclusion, UHRF1 is a master regulator of tumor progression in SCLC, promoting lineage stability, immune evasion, and metastatic spread. Its inhibition reprograms tumors toward an inflamed, less metastatic, and more immunogenic state. These findings establish UHRF1 as a compelling therapeutic target for overcoming the epigenetic and immune resistance barriers in small cell lung cancer.

overall_design: Gene expression profiling analysis of RNA-seq data from 1) NCI-H526 VC and UHRF1 KO   5-week orthotopic xenograft tumors in NSG mice, 2) NCI-H446 VC and UHRF1 KO 5-week orthotopic xenograft tumors in NSG mice, 3) mouse SCLC tumors from genetically engineered mouse models Tp53/Rb1 DKO (TR DKO) and Tp53/Rb1/Uhrf1 TKO (TRU TKO).

first: Yijun

last: Gu

first: Yasamin

last: Fazeli


title: CHD1 is a synthetic lethal vulnerability in MYC-driven breast cancer

city: Toronto

first: Brandon

middle: Alexander

last: Cho

state: ON

address: 25 Orde Street, Room 6-1001 MRS

institute: Lunenfeld-Tanenbaum Research Institute

summary: The MYC transcription factor is a key regulator of growth during development and a potent cancer driver when its expression is dysregulated. Strategies to inhibit MYC oncogenic activity would mark a significant advance, but decades of efforts to target MYC directly have not been fruitful. Understanding how MYC drives transformation and tumor growth may provide new therapeutic avenues in a variety of cancers. By intersecting two independent genome-wide screens, we identified loss of the chromatin remodeler Chromodomain-Helicase DNA-binding 1 (CHD1) as a potential synthetic lethal target in MYC-driven breast cancer. Knockdown of CHD1 in a xenograft model of MYC-driven breast cancer suppresses tumor growth in vivo. In tissue culture models, we found that knockdown of CHD1 suppresses cell proliferation and induces cell death, specifically when MYC is overexpressed. Mechanistically, we found that CHD1 is required to maintain an open chromatin landscape and a transcriptional program associated with cancer progression in MYC overexpressing breast cells. Follow-up experiments indicate that this synthetic lethality may arise from nucleolar stress and p53 activation. These findings provide new insights on the chromatin-level regulation of MYC-driven breast cancer and uncover CHD1 as a novel synthetic vulnerability and potential therapeutic target.

overall_design: RNA-seq profiling of non-transformed (MCF10A PE) and MYC-transformed (MCF10A PM) breast cancer cells investigating the effect of CHD1 knockdown (shCHD1) relative to control conditions (shGFP)

first: Giacomo

last: Furlan

first: Peter

last: Lin

first: Mélissa

last: Shen

first: Kirti

last: Mittal

first: Andrew

last: Mazzanti

first: Linda

middle: Z

last: Penn

first: Miguel

last: Ramalho-Santos


title: CHD1 is a synthetic lethal vulnerability in MYC-driven breast cancer [ATAC-seq]

overall_design: ATAC-seq of MYC-transformed (MCF10A PM) breast cancer cells to investigate the effect of CHD1 knockdown (shCHD1) relative to control conditions (shGFP)


title: A Robust Mouse Liver Organoid Platform Enables Sustained Multicellular Maturation and Fibrosis Modeling from a Single Tissue Sample

status: Public on Feb 27 2026

city: Taipa

first: Yingyu

last: Liang

address: Avenida Wai Long

country: Macau

institute: Macau university of Science and Technology

summary: Efficient isolation and culture of liver organoids are critical for studying liver fibrosis, liver regeneration and drug toxicity and screening. However, preserving mature hepatobiliary characteristics and concurrently incorporating fibrosis-producing hepatic stellate cells (HSCs) remains a significant challenge, often hindering the large-scale production of organoids capable of replicating key liver functions. Here, we report a robust 3D organoid culture system that enables simultaneous isolation and long-term propagation of primary hepatocytes, cholangiocytes, and HSCs from a single source of mouse liver tissue. By supplementing the Hep-Medium with Notch signaling inhibitor and dexamethasone, we achieved sustained organoid maturity, including stable albumin production, metabolic activity, and liver-specific gene expression, over multiple passages in culture. Quiescent HSCs within the system retained lipid droplets and could be activated into a myofibroblast-like phenotype, also called activated HSCs, via TGFβ stimulation. Activated HSCs impaired the proliferation and stemness, and induced epithelial-mesenchymal transition (EMT) of Hep-Orgs and Cho-Orgs, enabling in vitro liver fibrosis modeling. Optimized for minimal tissue input, this platform maximizes tissue utilization efficiency while preserving the liver’s heterogeneous cellular architecture. Its versatility supports diverse applications in liver disease modeling, drug discovery, and regenerative medicine.

overall_design: RNA-seq profiling of primary hepatocytes, P1/P5/P10 hepatocyte organoids, P0/P5/P10 cholangiocyte organoids and different morphologies of hepatocyte organoids.


title: Pulmonary Organoid Models Demonstrate Compositionally Driven Epithelial Plasticity and Immune Polarization

city: New Haven

first: Micha Sam

middle: Brickman

last: Raredon

state: Connecticut

address: 10th Amistad Street

department: Department of Anesthesiology

institute: Yale University

summary: Aberrant epithelial regeneration and immune remodeling are hallmarks of chronic lung diseases such as idiopathic pulmonary fibrosis (IPF), COPD, and post-viral syndromes. Yet how cellular context shapes these trajectories remains unresolved. We present a tunable, primary rat-derived lung organoid model that systematically varies immune, epithelial, and mesenchymal inputs to reveal how composition alone dictates epithelial plasticity and macrophage polarization. Across conditions, we observed the spontaneous emergence of disease-relevant transitional cell states, including Sox9⁺ stressed progenitors, RAS/AT0-like intermediates, and hillock-like cells, alongside distinct macrophage activation profiles. In mesenchyme-rich contexts, epithelial, immune, and mesenchymal crosstalk appeared to reinforce inflammatory signaling and stabilize transitional persistence, while immune-dominant inputs favored ATI-like repair and squamous remodeling. Notably, hillock-like cells displayed context-specific polarization and expressed immune-regulatory genes, suggesting a role as epithelial orchestrators that help calibrate inflammatory response during regeneration. Connectomic analysis revealed that regenerative outcomes were associated with dynamic multicellular signaling networks that integrate stress sensing, immune coordination, and epithelial fate. This platform provides a tractable system for modeling context-specific repair and regenerative mechanisms and could inform therapeutic strategies aimed at redirecting epithelial fate in chronic lung disease.

overall_design: Whole native rat lungs were enzymatically dissociated to generate heterogeneous starting populations containing epithelial, immune, and mesenchymal cells (PD_1, PD_2, PD_3) and sequenced. Additionally, primary immune and epithelial cells isolated via bronchoalveolar lavage (BAL) from native rat lungs were sequenced (BAL_1, BAL_2, BAL_3). Both PD and BAL suspensions were seeded into organoid culture and expanded for 10 days. Three organoid conditions were generated: PD_3D (100% PD), Mixed_3D (50:50 mix of PD and BAL), and BAL_3D (100% BAL). This design was intended to explore how varying the initial immune, epithelial, and mesenchymal composition shapes downstream cell fate, regenerative plasticity, and multicellular signaling.

first: Sophie E.

last: Edelstein

first: Satoshi

last: Mizoguchi

first: Maria

last: Tomàs Gracia

first: Nuoya

last: Wang

first: Vi

last: Lee

first: Hahram

last: Kim

first: Connor

last: Haynes

first: Colten

last: Danelski

first: Tomoshi

last: Tscuchiya

first: Maor

last: Sauler

first: Micha Sam Brickman


title: Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina

city: Bethesda

first: Matthew

last: Brooks

address: 6 Center Dr Bldg 6, Rm 303

institute: NIH


title: Transcriptional rewiring by enhancer methylation in CBFA2T3-GLIS2–driven pediatric acute megakaryoblastic leukemia [DNA methylation]

city: Little Rock

first: Akhilesh

last: Kaushal

state: Arkansas

address: One Children’s Way, Slot 512-43

department: Hematology/Oncology

institute: University of Arkansas for Medical Sciences

type: Methylation profiling by genome tiling array

summary: Chemotherapy resistance and relapse remain significant challenges in pediatric acute myeloid leukemia (pAML), particularly in acute megakaryoblastic leukemia (AMKL) driven by the CBFA2T3-GLIS2 (C/G) fusion. To investigate the epigenetic mechanisms underlying these challenges, we employed multi-epigenomic approaches to identify oncogenic enhancers at cis-regulatory elements (CREs) driving aberrant gene expression. This study analyzed DNA methylation profiles in C/G+ AML cell lines (M07e, WSU-AML) compared to non-C/G AML cell lines (KASUMI-1, ME-1, KG-1A). Additionally, we included primary hematopoietic cells, including CD34+ hematopoietic stem progenitor cells (HSCs) and CD41+ megakaryocytic progenitors (MKs). DNA methylation was profiled using the Illumina Infinium HumanMethylation930K BeadChip (MethylationEPICv2.0) across all samples.

overall_design: To explore the epigenetic mechanisms underlying these challenges, we employed multi-epigenomic approaches to identify oncogenic enhancers at cis-regulatory elements (CREs) that drive aberrant gene expression.This study analyzed DNA methylation profiles in the C/G+ AML cell line M07e, where we performed a CRISPR-based functional knockout of DNMT3B, comparing it to the control M07e cell line.

first: Samrat

last: Roy Choudhury

first: Jason

last: Farrar


title: Selective targeting of a histone-like silencer Sfx to the R6K conjugal transfer operon [ChIP-Seq]

status: Public on Feb 24 2026

city: Columbus

first: Irina

last: Artsimovitch

state: Ohio

address: 318 W 12th Ave

department: Microbiology

institute: The Ohio State University

summary: Conjugative plasmids drive bacterial evolution and the spread of antibiotic resistance, yet their gene expression must be silenced to protect the host. A histone-like protein H-NS represses many mobile and sedentary xenogenes but fails to silence the conjugal transfer vir operon of R6K, a prototype IncX plasmid. Instead, R6K encodes its own H-NS homolog, Sfx, to repress the vir operon. Here, we show that, unlike other plasmid silencers that target promoters, Sfx cooperates with Rho factor to arrest transcription elongation. ChIP-seq reveals that despite sharing similar DNA motifs and a preference for negative supercoiling, Sfx and H-NS occupy distinct niches: Sfx binds weakly to the chromosome but is enriched on the R6K vir operon while H-NS is excluded. We hypothesize that this selective targeting is mediated by Sfx-vir DNA interactions and phase separation. We show that Sfx binding to vir DNA critically depends on DNA topology but not on the target location. Our results suggest that Sfx forms stable nucleoprotein filaments that are impermeable to competitors and phase separates with R6K DNA to exclude H-NS. Our results suggest how functionally distinct histone-like proteins may achieve target specificity despite broad recognition motifs.

overall_design:
ChIP-seq assays for comparing the binding sites of H-NS and its homolog Sfx encoded on R6K plasmid in Escherichia coli. The sequences of all plasmids used in this study can be found in the accompanying manuscript.
ChIP-seq of RNA polymerase in E. coli carrying the Sfx deletion R6K plasmid to identify potential promoters in R6K.
RNA ChIP-seq assay to identify RNAs ChIPed by FLAG-tagged Sfx.

first: Bing


title: Selective targeting of a histone-like silencer Sfx to the R6K conjugal transfer operon [RNA-Seq]

summary: Conjugative DNA transfer is mediated by large membrane-spanning type IV secretion system (T4SS) complexes encoded by long plasmid operons (commonly called tra or vir). Conjugative IncX plasmids encode histone-like protein H-NS homolog as core gene. R6K, a prototype IncX plasmid, encodes its own H-NS homolog, Sfx, to repress the vir operon. Here, we show that, unlike other plasmid silencers that target promoters, Sfx cooperates with Rho factor to arrest transcription elongation. Our results show that Sfx mainly targets the R6K vir operon.

overall_design: RNA-seq profiling of E. coli harboring plasmid R6K derivatives to detect the targets of histone-like silencer Sfx.


title: IFNγ-independent control of Mycobacterium tuberculosis infection in rhesus macaques

status: Public on Feb 25 2026

first: Sivaranjani

last: Namasivayam

address: 33 North Drive

department: NIAID

summary: Control of Mycobacterium tuberculosis (Mtb) infection requires IFNγ in mice. In humans, IFNγ is critical for resistance to non-tuberculous mycobacteria (NTM), but its role in classic pulmonary tuberculosis is less clear. Here we block IFNγR1 signaling in rhesus macaques at different times post-infection. Short-term IFNγ blockade after tuberculoma formation rapidly reduced 18FDG-PET/CT scores of lung inflammation and changed macrophage gene expression. It also increased IFNβ, pDCs, plasma cells, killers and IFN-driven gene expression in neutrophils. Blockade started on the day of infection altered T and B cell responses and reduced cytokine levels in granulomas. Surprisingly, IFNγ blockade did not affect bacterial loads. We also find that patients with anti-IFNγ neutralizing autoantibodies develop extrapulmonary NTM disease, not pulmonary tuberculosis, despite immunological evidence of Mtb exposure. Thus, IFNγ has broad immunomodulatory effects during tuberculosis, especially on antiviral-like responses, but control of pulmonary Mtb infection does not require generating high levels of IFNγ.

overall_design: Male rhesus macaques, 3 years old, infecetd with ~40 CFU of Mycobacterium tuberculosis H37Rv. 45 days following ijfection, animals were treated with IFNgR blockade antibody or isotopye for 4 days. Granulomas were then isolated from each monkey and processed for scRNAseq using the 10X Genomics protocol

first: Shunsuke

last: Sakai

first: Keith

middle: D

last: Kauffman

first: Eduardo

last: Fukutani

first: Artur

middle: T

last: Queiroz

first: Christine

last: Nelson

first: Erin

middle: F

last: McCaffrey

first: Ploenchan

last: Chetchotisakd

first: Jay

last: Buchanan

first: Alan

last: Sher

first: Carl

middle: G

last: Feng

first: Joel

last: Ernst

first: Steven

middle: M

last: Holland

first: Katrin

last: Mayer-Barber

first: Bruno

last: Andrade

first: Christa

last: Zerbe

first: Laura

last: Via

first: Daniel

last: Barber


title: Integrating Trajectory Inference and Self-Explainable Predictive Models to Explore Cell State Transitions in Breast Cancer at Single-  Cell Resolution

city: Catanzaro

first: Rosamaria

last: Lappano

state: Cz

address: Viale Europa, Loc. Germaneto

department: Experimental and Clinical Medicine

country: Italy

institute: University "Magna Graecia" of Catanzaro

summary:
Breast cancer is characterized by a highly heterogeneous cellular environment composed of diverse malignant clones and components of the tumor microenvironment (TME) that collectively influence the progression of the disease. Single-cell RNA sequencing (scRNA-seq) offers a powerful tool to dissect this complexity, enabling high-resolution characterization of tumor heterogeneity and the functional interactions within the TME. Moreover, it supports the discovery of clinically relevant subpopulations and potential therapeutic targets. In this study, we present a novel scRNA-seq dataset from an infiltrating ductal breast cancer, profiling over 5,000 cells and identifying six distinct clusters spanning cancer and TME populations. To
explore the molecular drivers of cell state transitions, we integrate pseudotime trajectory inference with interpretable, tree-based machine learning. This approach enables the identification of key genes and expression thresholds associated with dynamic phenotypic shifts. Unlike black-box models, our framework yields transparent, rule-based insights into transcriptional reprogramming during tumor evolution. The resulting dataset, along with an accessible and transparent analytical pipeline, offers a valuable resource for the breast cancer research community and lays the groundwork for future studies aimed at refining molecular classification and precision therapy development.

overall_design: We analyzed single cell RNA-seq data from breast cancer tissue.


title: CSF1R inhibition plus chemotherapy induces systemic anti-tumor immune responses in triple negative breast cancer and sensitizes tumors to anti-PD-1 therapy by relieving resident memory T cell dysfunction [nanostring]

status: Public on Feb 23 2026

city: Portland

first: Lisa

last: Coussens

state: OR

address: 3181 SW Sam Jackson Park Rd

institute: Oregon Health and Science University

summary: Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease where limited therapeutic options are available. A significant correlation exists between presence of intratumoral macrophages, tumor progression, and poor outcomes in TNBC. Preclinical in vivo studies revealed that inhibition of myelomonocytic colony stimulating factor 1 (CSF1) or its receptor (CSF1R), plus cytotoxic therapy decreases primary tumor growth kinetics and pulmonary metastases by CD8+ T cell-dependent mechanisms. To evaluate safety and tolerability of this immune-based therapeutic strategy, we conducted a phase Ib/II clinical trial evaluating Pexidartinib (PLX3397), a small molecule CSF1R inhibitor plus Eribulin chemotherapy in patients with heavily pretreated metastatic TNBC. Correlate analyses from baseline revealed increased leukocyte activation biomarkers, increased presence of CD8+ and CD4+ T central memory cells, and increased PD-1 expression on CD4+ T cells in patients experiencing a partial response or stable disease, together providing evidence of enhanced anti-tumor immunity. We hypothesized that addition of either PD-1 and PD-L1-blockade following CSF1R inhibition and chemotherapy would lead to a further enhanced anti-tumor T cell response. To test this, we evaluated tumor-bearing MMTV-PyMT transgenic mice comparing addition of PD-1- or PD-L1-blockade to Pexidartinib/Paclitaxel therapy. This revealed tumor regression in ~60% of transgenic mice with combined PD-1, but not PD-L1-blockade. Analysis of mammary tumors from mice treated with the PD-1 combination revealed activation and expansion of short-lived effector and memory T cells, and unique clonally-expanded T cells not observed with the PD-L1-blockade combination. These clinical and preclinical findings together provide rationale for addition of CSF1/CSF1R inhibitors to chemotherapy and PD-1-blocakde to further improve outcomes for patients with BC.

overall_design: Expression of 750 genes from the nCounter Mouse PanCancer IO360 Nanostring panel was assessed for 5 different treatments, minimum two replicates per treatment.

first: Hope

middle: S

last: Rugo

first: Amanda

last: Poissonnier

first: Eivind

middle: V

last: Egeland

first: Wesley

last: Horton

first: Tiziana

last: Cotechini

first: Brian

last: Ruffell

first: Cecil

last: Gomes

first: Shamilene

last: Sivagnanam

first: Nicky

last: Belen

first: Dhaarini

last: Murugan

first: Nell

last: Kirchberger

first: Courtney

last: Betts

first: Motomi

last: Mori

first: Shivaani

last: Kummar

first: K

last: Blackwell

first: E

last: Mayer

first: Shelley

last: Hwang


title: CSF1R inhibition plus chemotherapy induces systemic anti-tumor immune responses in triple negative breast cancer and sensitizes tumors to anti-PD-1 therapy by relieving resident memory T cell dysfunction [luminex]

first: Lisa

last: Coussens

overall_design:
The Luminex platform was used to measure the abundance of 65 analytes in human blood plasma of women with metastatic triple-negative breast cancer
NOTE: characteristics: sourceID' id  indicates same sample source across timepoints
NOTE: 'characteristics: Timepoint' variable indicates which timepoint from sample source the data is from

first: Hope

last: Rugo


title: Fine-tuning ERK activity enables proliferation-differentiation balance during lineage specification of human embryonic stem cells

city: HangZhou

first: WeiKang

last: Meng

state: ZheJiang

address: A4 Floor, Teaching Building, School of Medicine, Zijingang Campus, Zhejiang University

institute: ZheJiangUniversity

summary: It is well documented that differentiation of stem cells is generally associated with and facilitated by an elongated cell cycle. However, for lineage specification requiring high ERK activity, which also promotes proliferation, it is unclear how stem cells simultaneously negotiate the “proliferation-differentiation” decision. Here we investigate this question using multiplex quantitative live-cell imaging to track embryonic stem cells (ESC) differentiation into mesendoderm (ME) lineage with high ERK activity. We show that ERK activity increase manifested by a heightened ERK oscillation frequency drove robust ME differentiation accompanied by a modest cell cycle acceleration. We profile the responses of ME differentiation and cell cycle length as a function of a synthetic ERK oscillatory activity gradient. Our results reveal that these two processes took place in distinct ranges of ERK oscillation frequency, with ME differentiation requiring higher level for ERK oscillation to secure efficient ME protein translation. Interactions between gastrulation morphogens recapitulated an ERK oscillation gradient, potentiating heterogeneous ME fates while maintaining a comparable level of proliferation. Our study thus provides mechanistic insights into how ERK fine-tunes proliferation and differentiation during cell fate specification

overall_design: hESCs were treated with CHIR99021 in combination with different concentrations of the Ulix inhibitor. Polysome profiling was performed by sucrose gradient ultracentrifugation, and RNA was extracted from pooled gradient fractions for RNA-seq analysis. The collected fractions included CHIR-total-RNA and gradient pools CHIR-2–3, CHIR-4–5, CHIR-6–7, and CHIR-8–11, which represent RNA populations ranging from free/lowly translated mRNAs to heavy polysome-associated mRNAs. Sample names containing labels such as “CHIR-U0_15” indicate cells treated with CHIR99021 together with 0.15 μM Ulix inhibitor; additional samples include treatments with 1.25 μM and 5 μM Ulix.

first: Chenyang

last: Ma

first: Weikang


title: CSF1R inhibition plus chemotherapy induces systemic anti-tumor immune responses in triple negative breast cancer and sensitizes tumors to anti-PD-1 therapy by relieving resident memory T cell dysfunction [tumor]

overall_design: genomic DNA extracted from mice from 7 treatments and two timepoints was amplified for TCRb library and sequenced

first: Amanda

last: Poissonnier

first: Eivind

last: Egeland

first: Wesley

last: Horton

first: Tiziana

last: Cotechini

first: Brian


title: CSF1R inhibition plus chemotherapy induces systemic anti-tumor immune responses in triple negative breast cancer and sensitizes tumors to anti-PD-1 therapy by relieving resident memory T cell dysfunction [lung]

last: Ruffell

first: Cecil

last: Gomes

first: Shamilene

last: Sivagnanam

first: Nicky

last: Belen

first: Dhaarini

first: Nell


title: CSF1R inhibition plus chemotherapy induces systemic anti-tumor immune responses in triple negative breast cancer and sensitizes tumors to anti-PD-1 therapy by relieving resident memory T cell dysfunction [lymph node]

last: Murugan

last: Kirchberger

first: Courtney

last: Betts

first: Motomi

last: Mori

first: Shivaani

first: K

first: E


title: CSF1R inhibition plus chemotherapy induces systemic anti-tumor immune responses in triple negative breast cancer and sensitizes tumors to anti-PD-1 therapy by relieving resident memory T cell dysfunction [blood]

first: Lisa

first: Hope

last: Kummar

last: Blackwell

last: Mayer

first: Shelley

last: Hwang


title: The timing of antenatal glucocorticoids determines the receptor sensitivity in preterm infants

status: Public on Feb 21 2026

city: Leioa

first: Mariana

last: Astiz

state: Bizkaia

address: Barrio Sarriena s/n, Science Park of the UPV/EHU, Sede Building, 3rd floor

institute: Achucarro Basque Center for Neuroscience

summary: Approximately 15 million babies are born too early each year, corresponding to a global preterm birth rate of about 11%. The antenatal glucocorticoid (aGC) therapy is indicated to more than 90% of their mothers when there is a risk of preterm delivery between 24 and 34 weeks of gestation. Synthetic GCs (sGC) accelerate fetal lung maturation and reduce the risk of respiratory distress syndrome (RDS), the leading cause of mortality in preterm infants. However, this treatment has been associated with an increased vulnerability to develop neurobehavioral and immune disorders later in life, effects attributed to permanent changes in the stress axis activity and in the homeostasis of endogenous GCs. In the present study, we assessed the effect of the antenatal administration of aGCs in preterm babies with a special focus on the influence of the time of exposure. We found that preterm infants exposed to aGCs in the late evening (i.e.: out-of-phase relative to the maternal daily cortisol rhythms) exhibited reduced GR sensitivity in peripheral blood mononuclear cells (PBMCs). By comparing the transcriptome of PBMCs we found significant changes in genes involved in antibody production and B cell signaling, leucocyte migration and proliferation, antigen presentation and cellular stress responses. Our data suggests that the aGCs exposure in the morning, in-phase and aligned with the maternal GC rhythms, would be advisable in the clinics to minimize these secondary effects and improve the capacity of preterm infants to fight against pathogens during the first weeks of life.

overall_design: The RNA samples were obtained from peripheral blood mononuclear cells (PBMCs) from 13 term babies (controls) and 34 premature babies exposed to antenatal glucocorticoids (aGCs). We further devided the aGCs exposed babies' samples depending on the time of day in which the mother was exposed. Babies exposed to aGCs in the morning are grouped as in-phase (IP, n=17) (with the maternal circadian rhythms) and babies exposed in the evening are grouped as out-of-phase (OP, n=17).

first: Ingmar

last: Fortmann

first: Jan

middle: H

last: Britsemmer

first: Marianne

last: Lehmann

first: Natalie

last: Taege

first: Henrik

last: Oster

first: Henriette

last: Kirchner

first: Christoph

last: Haertel


title: VISTA Drives Pancreatic Tumor Progression Through Modulation of The Tumor-Associated Macrophage Polarity

city: Seoul

first: Suk-Kyung

last: Shin

address: 103 Daehak-ro, jongno-go

country: South Korea

institute: Seoul National University

summary: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies due to its highly immunosuppressive tumor microenvironment (TME), which limits effective therapeutic interventions. Here, we demonstrate that V-domain immunoglobulin suppressor of T cell activation (VISTA) plays a crucial role in orchestrating macrophage polarity within the PDAC TME. Using murine PDAC models, we show that VISTA deficiency markedly impairs tumor growth, leading to reduced tumor volumes and prolonged survival. Mechanistically, VISTA loss reprograms tumor-associated macrophages (TAMs) from an immunosuppressive, secreted phosphoprotein 1(SPP1) expressing phenotype to a pro-inflammatory, C-X-C motif chemokine ligand 9 (CXCL9) expressing subtype. This switch enhances the recruitment of C-X-C motif chemokine receptor 3 (CXCR3) positive CD8+ T cells, reducing their exhaustion and sustaining their cytotoxic activity. Additionally, VISTA-deficient TAMs exhibit increased antigen cross-presentation, further amplifying CD8+ T cell response against tumors. These findings are corroborated by human single cell RNA-seq datasets, which suggest a conserved mechanism of VISTA-mediated immune modulation in PDAC TME. By elucidating the upstream role of VISTA in driving Cxcl9:Spp1 macrophage polarity and T cell dynamics, this study highlights VISTA inhibition as a promising therapeutic strategy to reshape the TME, augment CD8+ T cell function, and enhance anti-tumor immunity in PDAC.

overall_design:
To investigate how VISTA deficiency impacts the immune-oncologic landscape of PDAC, we utilized a syngeneic orthothopic model comparing tumor growth between wild-type (WT) and VISTA-deficient mice.
We validated reduction of pancreatic tumor via treatment of anti-VISTA antibody in WT mice.
Using anti-CSF1R model, we identified a population that expresses high VISTA expression.
We then performed gene expression profiling analysis using data obtained from RNA-seq of pancreatic tumors in WT and Vsir-/- mice on day 28 post-inoculation.


title: Transcriptomic study of the Drosophila midgut during larval development

status: Public on Mar 07 2026

city: Cologne

first: Gilles

last: Storelli

address: Joseph Stelzmannstrasse 26

department: CECAD Research Center

institute: University of Cologne

summary: The main goal of this study was to characterize the transcriptome of the Drosophila midgut during larval development. Larval midguts were collected on three different days during development for RNA extraction and mRNA-seq. Our data show that a drastic transcriptomic change occurs in the midgut between the third and fourth day of larval life, corresponding to the entry into the third instar.

overall_design: w1118 embryos were collected after overnight egg laying and transferred in batches of 40 to polystyrene vials containing a yeast-only diet (“day zero”). Larvae were then collected on days two, three and four for midgut dissection. Total RNA was extracted from 60, 30 or 10 midguts for larvae aged two, three or four days, respectively. mRNA sequencing was performed on five biological replicates per time point.

first: Clara

last: Lefranc

first: Ali

last: Abdallah


title: Endothelial TLR4 signaling drives tissue inflammation, Claudin-5 internalization, and vascular barrier breakdown in a mouse model of neonatal meningitis

status: Public on Feb 20 2026

city: Baltimore

first: Amir

last: Rattner

state: MD - Maryland

address: 725 North Wolfe St.

institute: Johns Hopkins University

type: Non-coding RNA profiling by high throughput sequencing

summary: Neonatal bacterial meningitis is a leading cause of infant morbidity and mortality, yet the molecular and cellular basis of the leptomeningeal response to infection remains poorly defined.  Here, we study a mouse model of neonatal E. coli meningitis, combining conditional gene knockouts, leptomeningeal single-nucleus RNA sequencing, and endothelial cell culture to explore the role of Toll-like receptor 4 (TLR4) signaling in the host response to infection.  Deletion of Tlr4 in non-myeloid cells dramatically reduced the inflammatory response in all leptomeningeal cell types and abrogated the infection-associated increase in vascular permeability.  In a brain endothelial cell line (bEnd.3 cells), exposure to E. coli triggered NF-κB activation, selective internalization of Claudin-5, and increased monolayer permeability, responses that were eliminated by Tlr4 knockout.  RNA-seq showed that TLR4 controls an NF-κB–driven transcriptional program that orchestrates the endothelial response to E. coli.  These findings reveal multiple TLR4-dependent host responses to neonatal Gram-negative bacterial meningitis.

overall_design: Here, we study a mouse neonatal meningitis model and cultured CNS ECs (bEnd.3 cells) to test whether endothelial-intrinsic TLR4 signaling (i) orchestrates the multi-cellular response of the leptomeninges to infection and (ii) regulates Cldn5 trafficking and vascular barrier function. In the present work, we (i) profiled cell-type–specific responses in the leptomeninges from WT, endothelial Tlr4 conditional knockout mice (Tlr4ECKO), and macrophage Tlr4 conditional knockouts (Tlr4MKO) using single nucleus (sn)RNA-seq; (ii) performed wholemount immunostaining to quantify ICAM-1 induction, extravascular tracer leakage, and macrophage activation in vivo; (iii) tracked Cldn5 redistribution and NF-κB nuclear translocation in bEnd.3 cells exposed to E. coli; (iv) generated CRISPR Tlr4KO bEnd.3 lines to assess the TLR4 dependence of NF-κB activation, tight-junction dynamics, and barrier permeability; (v) quantified Cldn5 colocalization with junctional, plasma-membrane, and endosomal/lysosomal markers; (vi) defined TLR4-dependent transcriptional programs in bEnd.3 cells. The results of these experiments establish a framework for understanding the pathophysiology of neonatal meningitis that establishes endothelial TLR4 signaling as a central regulator of both the multicellular leptomeningeal response to infection and Cldn5 trafficking and junctional integrity.

first: Philip

last: Seegren

last: Smallwood

first: Yanshu

last: Wang

first: Jeremy

last: Nathans


title: The ubiquitin ligase CBL and Fas-associated factor 2 cooperate to regulate the innate immune response to M. tuberculosis

city: Davis

first: Tina

last: Truong

state: California

address: One Shields Ave

institute: UC Davis

summary: As a first line of host defense, macrophages must be able to effectively sense and respond to diverse types of pathogens, and while a particular response may be beneficial in some circumstances, it can be detrimental in others. Upon infection, Mycobacterium tuberculosis (Mtb) induces proinflammatory cytokines and activates antibacterial responses. Surprisingly, Mtb also triggers antiviral responses that actually hinder the ability of macrophages to restrict Mtb growth. In Mtb-infected macrophages, the ubiquitin ligase CBL suppresses antiviral responses and preserves the antibacterial capacity of the macrophage. However, the mechanisms by which CBL regulates immune signaling are unknown. We found that CBL controls responses to multiple immune stimuli and broadly suppresses the expression of antiviral response genes. We used mass-spectrometry to identify potential CBL substrates, and found, in total, over 46,000 ubiquitylated peptides in Mtb-infected macrophages, including roughly 400 peptides with CBL-dependent ubiquitylation. We then performed genetic interaction analysis of CBL and its putative substrates, and identified the Fas associated factor 2 (FAF2) adapter protein as a key signaling molecule downstream of CBL. Together, these analyses reveal thousands of new ubiquitin-mediated signaling events and identify an important new regulator immune signaling.

overall_design: RNA-seq profiling of differentiated WT THP-1 cells and their knockdown derivative (shCBL) mock infected or infected with lpqN Mtb at 6 hours post infection.

first: Abigail

last: Ray

first: Kelsey

last: Martin

first: Nicholas

last: Bates

first: Michelle

last: Salemi

first: Brett

last: Phinney

first: Bennett

last: Penn


title: Single cell Transcriptomes Reveals Aberrant Airway cell-cell interations in Pulmonary Fibrosis

city: London

first: Probir

last: Chakravarty

address: 1Midland Road

institute: Francis Crick

summary: We used single-cell RNA-seq to compare epithelial and immune cell populations in non-manipulated brushings of the proximal airway mucosa in patients newly-diagnosed with IPF (n=9) as compared to healthy controls (n=7). 60,313 cells were profiled including 22,487 cells from healthy controls and 37,826 cells from patients with IPF.

overall_design: Exploratory single-cell RNA-seq analysis of proximal airway mucosa cell populations from patients with idiopathic pulmonary fibrosis (IPF) and health controls.

first: Richard

middle: J

last: Hewitt

first: Anne

last: O'Garra

first: Clare

last: Lloyd


title: Multiomic single nuclei profiling of a mouse model of Alzheimer’s disease reveals that ACSS2 confers neuronal resilience to tauopathy

city: Philadelphia

first: Gregory

last: Donahue

address: 3400 Civic Center Blvd, Bldg 421

department: Cell & Developmental Biology

institute: The University of Pennsylvania

summary: This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [4]

status: Public on Feb 19 2026

city: St Louis

first: Fang

middle: R

last: Zhao

state: MO

institute: Washington University in St Louis

summary: Functional gastrointestinal (GI) tract disorders affect a substantial proportion of the global population and are often preceded by intestinal infections that cause injury to enteric neurons and glia through unrestrained immune responses. However, the mechanisms that limit infection-induced inflammation and protect the enteric nervous system remain poorly understood. Here, we investigated neuron-glia-macrophage interactions after West Nile virus (WNV) infection, a model neurotropic virus that causes GI tract dysmotility via injury of enteric neurons through a T cell-mediated cytolytic mechanism. In response to WNV infection, resident muscularis macrophages upregulate antiviral, proinflammatory, and immunomodulatory genes. However, pharmacological depletion of resident macrophages did not affect viral burden in the GI tract, but rather reshaped the enteric glial response to WNV, resulting in excessive production of T cell and neutrophil chemoattractants. This amplified recruitment of immune cells worsened enteric neuronal injury. Together, our findings identify resident muscularis macrophages as key regulators of glia-driven inflammation during enteric viral infection and reveal their role in protecting enteric neurons from immune-mediated damage.

overall_design: Translating ribosomal affinity purification (TRAP) of the muscularis externa of West Nile virus (WNV)  Plp1CreER;NuTRAP mice treated with either anti-CSF1R (to deplete resident macrophages) or isotype control antibody  was performed at 6 days post infection to identify factors regulating response of enteric glia in distal part of small intestine to WNV in the absence of resident macrophages. Isolated immunopreciptated ribosome-bound mRNA from enteric glia was used for high-throughput sequencing.

first: Hana

last: Janova

first: Ali

last: Akgul

first: Meredith

last: Schatz

first: Daniel

last: Alligood

first: David

last: Alvarado

first: Larissa

middle: B

last: Thackray

first: Thaddeus

last: Stappenbeck

first: Michael

last: Diamond


title: Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [2]

overall_design: Translating ribosomal affinity purification (TRAP) of the muscularis externa of West Nile virus (WNV) and mock-infected Plp1CreER;NuTRAP mice was performed at 6 days post infection to identify factors regulating response of enteric glia in distal part of small intestine to WNV. Isolated immunopreciptated ribosome-bound mRNA from enteric glia was used for high-throughput sequencing.


title: Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [1]

overall_design: Sorting of resident macrophages from the muscularis externa of West Nile virus (WNV) and mock-infected CX3CR1CreER;YFP mice was performed at 6 days post infection to identify factors regulating response of resident muscularis macrophages in distal part of small intestine to WNV. Isolated  mRNA from resident muscularis macrophages was used for high-throughput sequencing.


title: Macrophage-glia interactions regulate immune-damage to enteric neurons during West Nile virus infection [3]


title: The microRNA profiles of extracellular vesicles (EVs) from  sympathetic neurons.

city: Tokyo

first: Takaaki

last: Tamura

address: 6-7-1 Nishishinjuku, Shinjyuku-ku

institute: Tokyo Medical University

summary: Emerging evidence suggests that the autonomic nervous system contributes to tumor progression, but the molecular basis of nerve–tumor communication remains unclear. Here, we performed NGS analysis to investigate the microRNA (miRNA) profiles within EVs from sympathetic neurons(GSE313037) and breast cancer cells.

overall_design: To investigate the EV contents derived from breast cancer cells, we prepared EVs from  RMT1 cells. EVs were isolated from culture supernatant using ultracentrifugation.

first: Marta

last: Prieto-Vila

first: Takahiro

last: Ochiya


title: Acute hormonal signaling-induced 3D chromatin loop reorganization controls adipocyte thermogenesis [Micro-C human]

status: Public on Feb 17 2026

city: Boston

first: Kaifu

last: Chen

state: MA

address: 300 Longwood Ave

department: Cardiology

institute: Boston Children's Hospital

summary: Recent molecular advancements have revolutionized our understanding of the role of three-dimensional (3D) genome organization in gene regulation. Yet, the impact of acute hormonal signaling on reshaping genome structure and its consequences for metabolic processes remain largely unexplored. β3-adrenergic receptor (β3-AR) hormonal signaling is imperative for brown adipose tissue (BAT) thermogenesis. Here, we demonstrate that β3-AR signaling induces rapid reorganization of fine-scale genome architecture in murine and human brown adipocytes within four hours. High-resolution Micro-C profiling reveals dynamic chromatin loop formation associated with activation of thermogenic genes. Mechanistically, β3-AR signaling promotes p18Hamlet/SRCAP complex assembly, catalyzing incorporation of the histone variant H2A.Z into nucleosomes. ATAC-sequencing reveals that H2A.Z enhances chromatin accessibility at loop anchors, supporting loop formation by facilitating the recruitment of looping factors such as the Mediator complex. Disruption of H2A.Z compromises dynamic chromatin looping and transcriptional activation of thermogenic genes in both species. Mice with BAT-specific H2A.Z deficiency exhibit reduced thermogenic activity and impaired glucose tolerance. Revisiting genome-wide association study analysis reveals that H2A.Z-occupied loops are linked to genetic variants associated with obesity and its related metabolic disorders. Together, these findings highlight the rapid adaptability of 3D genome organization to acute β3-AR signaling and its critical role in brown adipocyte thermoregulation.

overall_design: We performed high-resolution Micro-C in vehicle-treated control, forskolin (FSK)-trated control, and FSK-treated H2A.Z knockdowon (KD) primary human brown adipocytes to assess 3D genome reorganization during thermogenesis and the impact of H2A.Z KD on chromatin loop reorganization in humans.

first: Yang

last: Zhang

first: Rongbin

last: Zheng

first: Tadataka

last: Tsuji

first: Chih-Hao

last: Wang

first: Xiangyu

last: Liu

first: Yu-Hang

last: Xing

first: Justin

last: Darcy

first: Matthew

last: Lynes

first: Morten

last: Lundh

first: Rini

last: Arianti

first: Rui

last: Dong

first: Brice

last: Emanuelli

first: Miguel

middle: N

last: Rivera

first: Endre

last: Kristóf

first: Ronald

last: Kahn

first: Ferenc

last: Győry

first: Yu-Hua

last: Tseng