title: Effect of hepatic FPN ablation on the liver transcriptome in mice

city: Jeonju

first: Chang Yeob

last: Han

address: 20, Geonji-ro, Deokjin-gu

department: School of Pharmacy

institute: Jeonbuk National University

summary: Iron overload has emerged as a key risk factor for MASLD and metabolic disorders. We explored the effects of hepatocyte-specific knockout of ferroportin (FPN), the only known iron exporter, on the pathogenesis of MASLD and the associated metabolic dysfunction. To investigate the molecular basis, we carried out RNA-sequencing analysis using liver samples from littermate control and hepatocyte-specific Fpn KO mice.

overall_design: RNA-seq profiling of the liver from littermate control and hepatocyte-specific FPN KO mice fed a high-fat diet

first: Hye Jin

last: Jo

first: Ayoung

last: Kim


title: Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells [methylation]

status: Public on Apr 14 2026

city: MADRID

first: Ignacio

last: Heras-Murillo

state: MADRID

address: c/Melchor Fernandez Almagro, 3

country: Spain

institute: CNIC

summary: Activation of dendritic cells (DCs) is linked to increased glycolysis. However, the role of the mitochondrial electron transport chain (ETC) in conventional DC subset function is poorly defined. Here, we revealed that immunogenic activation elevates late oxygen consumption in cDC1s, but not cDC2s. To investigate the relevance of the ETC in DC immunogenicity, we generated mice with impaired ETC complex III function in DCs. ETC complex III impairment attenuated poised or adjuvant-triggered cDC1 activation, migration and capability to prime T cells for anti-cancer immunity, while it had a mild effect on cDC2s. Mechanistically, loss of complex III in cDC1s led to a deregulated redox and metabolite balance causing DNA hypermethylation of PU.1-binding regions. This DNA hypermethylation diminished early stimulus-induced gene expression linked to immunogenic responsiveness of cDC1s, which was rescued via ectopic expression of alternative oxidase. Our findings show how the ETC differentially regulates the immunogenic function of cDC subsets.

overall_design: cDC1s or cDC2s from Uqcrqf/f or Itgax-Uqcrqf/f mice were FACS sorted, the  DNA purified and bisulfite converted. Infinium Methylation BeadChip arrays (Illumina) were used to analyze DNA methylation.

first: Stefanie

middle: K

last: Wculek

first: Josep

last: Calafell-Segura

first: Esteban

last: Ballestar

first: David

last: Sancho


title: Adaptor protein CIN85 potentiates migration of osteosarcoma cells

city: Brno

first: Lucia

last: Knopfova

address: Kamenice 5

department: Department of Experimental Biology

country: Czech Republic

institute: Faculty of Science, Masaryk University

type: Expression profiling by high throughput sequencing

summary: The adaptor protein CIN85, encoded by the SH3KBP1 gene, is a member of the CIN85/CMS family of adaptor molecules involved in many signaling pathways. CIN85 functionally contributes to different biological processes in normal and cancer cells, such as vesicle-mediated transport, cell adhesion, migration, and invasiveness. In this study, we found that the expression of CIN85 was elevated in osteosarcoma compared to normal bone, and in metastases compared to primary bone tumors. Overexpression of CIN85 in osteosarcoma cell lines enhanced their migration and collagen invasion while silencing CIN85 suppressed cell migration. We used human osteosarcoma HOS cells with the overexpression of CIN85 or its knockdown to study the transcriptomic changes induced by this protein. Differentially expressed genes were enriched in cell proliferation, apoptosis, cell differentiation, extracellular matrix, adhesion, focal adhesion, tight junctions, and cell migration. Several abundant signaling pathways involved in tumorigenesis were identified, including NF-κB, TNF, MAPK, Wnt, PI3K/Akt/mTOR, TGF, and VEGF.

overall_design: RNA-seq analysis of the human osteosarcoma HOS cells with overexpression of knockdown of the adaptor protein CIN85. CIN85-overexpressing cells were obtained by the transfection with pRc/CMV2-Rukl plasmid (https://doi.org/10.1093/carcin/bgs228), mock-transfected cells were used as a control. CIN85 was silenced by the specific siRNA, and non-targeting siRNA was used as a control.

first: Iryna

last: Horak

last: Knopfová


title: Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells [RNA-seq]

overall_design: 50 ug poly(I:C) LMW and 50 ug R848 or the control PBS were intravenously administered into Uqcrqf/f or Itgax-Uqcrqf/f mice and, after 1.5 hours, the spleen  was harvested and processed. CD8+ cDC1 and CD11b+ cDC2 were FACS sorted, the RNA extracted and used for RNA sequencing.


title: Mitochondrial metabolism regulates the immunogenic responsiveness of dendritic cells [ATAC-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: cDC1s or cDC2s from Uqcrqf/f or Itgax-Uqcrqf/f mice were FACS sorted and used for ATAC sequencing.

first: Diego

last: Mañanes


title: Transcriptomic  characterization of Wild type mouse Embryonic Stem Cells (mESCs),  β-actin Knock out mESC and upon rescue with a nuclear localization signal  β-actin

status: Public on Apr 13 2026

city: Abu Dhabi

first: Piergiorgio

last: Percipalle

state: abu dhabi

address: NYUAD Saadiyat Island

country: United Arab Emirates

institute: Biology

summary: Pluripotency and lineage commitment in embryonic stem cells depend on coordinated regulation of chromatin architecture and extracellular matrix (ECM) signaling. Here, we identify nuclear β-actin as a key regulator linking these processes in mouse embryonic stem cells. Loss of β-actin disrupts core pluripotency factors, including Oct4 and Sox2, and causes broad transcriptional changes, while nuclear re-expression rescues these defects. Chromatin accessibility analysis revealed reduced accessibility at regulatory regions of pluripotency genes, consistent with impaired chromatin remodeling. β-actin depletion also altered ECM-related gene expression, matrix properties, and cellular biomechanics, leading to impaired self-renewal, skewed lineage specification, and defective differentiation, particularly reduced neuronal potential and increased mesodermal-like fate bias. In vivo, β-actin loss restricted teratoma growth and compromised tri-lineage differentiation. Together, these results define nuclear β-actin as an important regulator of chromatin accessibility, ECM-dependent signaling, and stem cell fate.

overall_design: RNA-seq Profiling of mESC Wild type, Knock out β-actin, and Nuclear Localization signal β-actin rescue

first: Nadine

last: Hosny El Said

first: Colin

last: Campbell

first: Amani

last: Nuairi

first: Sabrina

last: Desbordes


title: Pilot NanoString targeted mRNA profiling of neonatal saliva following prenatal opioid exposure

city: Boston

first: Tomoko

last: Kaneko-Tarui

state: Massachusetts

address: 800 Washington St., Box #394

department: Women, Mother + Baby Research Institute

country: USA

institute: Tufts Medical Center

summary: This study profiles targeted mRNA expression in neonatal saliva to investigate the sex-specific effects of prenatal opioid exposure. Saliva samples collected within 48 hours of birth from opioid-exposed and non-exposed neonates were analyzed using the NanoString nCounter Analysis System with a custom CodeSet targeting 72 genes, including housekeeping genes. Raw RCC files are provided for all assay instances, and processed data are provided as normalized, log2-transformed expression values for the QC-passed samples included in the final analysis.

overall_design: Neonatal saliva samples were collected within 48 hours after birth from opioid-exposed and non-exposed neonates born at >=34 weeks gestation. Total RNA was extracted and profiled using the NanoString nCounter Analysis System with a custom CodeSet targeting 72 genes, including housekeeping genes. A total of 36 assay instances were generated. Most assay instances represented independent neonatal saliva samples from different patients, while two biological samples were assayed more than once using newly extracted RNA from the same sample. Eighteen unique neonatal saliva samples passed quality control and were included in the final analysis. Raw RCC files for all assay instances are provided as supplementary files. The processed expression matrix contains normalized, log2-transformed expression values for the 18 QC-passed samples only.

first: Elizabeth

last: Yen


title: Long telomeres induce a genome-wide transcriptional response in budding yeast

city: Newcastle upon Tyne

last: Lydall

address: Cookson Building, Medical School, Framlington Place

country: United Kingdom

institute: Newcastle University

summary: Eukaryotes maintain telomere length within a defined range. While short telomeres are known to activate DNA damage responses and limit cell proliferation, long telomeres are associated with extended proliferative capacity, but their broader cellular consequences remain less well understood. In budding yeast Saccharomyces cerevisiae, long telomeres have been shown to influence gene expression at specific loci, but whether long telomeres affect transcription genome-wide has not been reported. Here, we analysed the transcriptomes of diploid yeast strains in a single lineage in which long telomeres were initially generated by a rif2delta mutation and subsequently inherited through successive rounds of mitosis and meiosis in the absence of this mutation. We show that strains with long telomeres exhibit a distinct gene expression profile, enriched in transcripts encoding membrane transporters. Both up- and down-regulated genes were distributed across the genome, arguing against a purely telomere-proximal effect on gene expression. Affected genes were enriched for Rap1 binding sites, consistent with a model in which long telomeres alter the availability of telomere-associated transcriptional regulators such as Rap1 and thereby affect gene expression at non-telomeric binding sites for these regulators. The magnitude of transcriptional changes was greatest in strains with the longest telomeres. Together, our findings demonstrate that long telomeres induce a genome-wide transcriptional response that accompanies inherited long telomeres across generations but diminishes as telomeres shorten.  These types of transcriptional changes may also occur in other eukaryotes, including humans, where long telomeres can be inherited and are associated with disease.

overall_design: RNA-seq profiling of Saccharomyces cerevisiae strains with different telomere lengths: wild-type (WT/WT) with normal telomeres, rif2delta heterozygous diploid with elongated telomeres (WT/rif2delta), and two successive generations of wild-type descendants of the WT/rif2delta diploid that inherited long telomeres (WT/WT_long1, WT/WT_long2). Three biological replicates per genotype (12 samples total).

first: Vasilisa

last: Sidarava


title: Fra2 role in PDAC response under MRTX-1133 treatment

city: Columbus

first: Gian Luca

last: Rampioni Vinciguerra

state: OH

address: 460W 12th Avenue

department: Cancer Biology and Genetics

institute: The Ohio State University

summary:
Fra2 is involved in the stress adaptivity of PDAC cells. We explored its possible role under the administration of the KRAS-inhibitor MRTX-1133
We used Affymetrix analysis to identify the downstream targets of Fra2 transcriptional activity under MRTX-1133 treatment in AsPC-1 cells

overall_design: We compared the transcriptome of the following AsPC-1 cells: wild-type untreated, wild-type resistant (obatined with continuous administration of escalating doses of MRTX-1133), FRA2KO untreated and FRA2KO (50nM) MRTX-1133 treated.

first: Giovanni

last: Nigita


title: H3K9me3 controls epidermis development by repressing RNA Pol II activity on key promoters and enhancers [CUT&Run - Temporal]

city: Ithaca

first: Chris

middle: Ke

last: Bai

state: NY

address: 526 Campus Rd

department: MBG

institute: Cornell University

summary: Histone H3 lysine 9 trimethylation (H3K9me3) is a heterochromatin mark important for silencing repetitive DNA elements and for repressing lineage-inappropriate genes during early murine development, but its role in later organogenesis remains understudied. Here, we simultaneously target three histone methylases, Suv39h1, Suv39h2 and Setdb1, to deplete H3K9me3 specifically in developing epidermis. H3K9me3 loss blocks epidermis morphogenesis, resulting in defective cell differentiation, impaired barrier function, disrupted hair follicle formation, and failed Merkel cell specification. Single cell transcriptomic analysis reveals epidermal cells with mixed lineage identity and perturbed cell-type specific gene programs, including cell cycle, extracellular matrix, cytoskeleton, and metabolism. Using our recently developed approach, PReCIS-seq, we present the first cell-type specific, genome-wide landscape of transcriptionally engaged RNA polymerase II (RNA Pol II) in intact tissue following H3K9me3 depletion. We find that H3K9me3-enriched islands restrict inappropriate RNA Pol II activity at select developmentally regulated enhancers and promoters. This work highlights the indispensable role of H3K9me3, mediated by its three major histone methyltransferases, in regulating lineage diversification and developmental progression during mouse organogenesis.

overall_design: Epcam+α6+ epidermal cells were sorted from E12.5, E14.5 and E16.5 wild type mouse embryos for CUT&RUN profiling. Anti-H3K9me3 antibody was used for experimental group and anti-IgG antibody was used for control group.

first: Tudorita

last: Tumbar


title: Carbohydrate responsive element binding protein promotes colorectal carcinogenesis by regulating the Wnt/beta-catenin pathway

city: Shanghai

first: Ming

last: Feng

address: 280 S. Chongqing Road

department: Department of Biochemistry and Molecular Cell Biology

country: China

institute: Shanghai Jiao Tong University School of Medicine

summary: ChREBP is a glucose-responsive transcription factor involved in glycolysis and de novo lipogenesis. Elevated ChREBP levels were observed in human colorectal cancer (CRC) samples and correlated with poor 5-year survival rates in patients. To investigate the role and mechanism of ChREBP in colorectal carcinogenesis in vivo, we used ChREBP knockout mice, which were intraperitoneally injected with azoxymethane (AOM) followed by dextran sulfate sodium (DSS) in drinking water. In the AOM/DSS-induced colorectal cancer model, carcinogenesis was reduced in ChREBP null mice. In the initial phases of colorectal carcinogenesis, ChREBP deficiency was associated with diminished epithelial cell proliferation and a lower number of aberrant crypt foci (ACF), but it had no impact on DNA damage or the severity of colitis. The key transcription factor beta-catenin and Wnt target gene expression were both decreased in the colons of ChREBP null mice and in ChREBP-knockdown Caco-2 colorectal cancer cells. In vitro studies showed that ChREBP knockdown promoted beta-catenin phosphorylation and reduced beta-catenin levels and nuclear localization in Caco-2 cells. Conversely, ChREBP overexpression was sufficient to promote beta-catenin accumulation, nuclear localization, and transcriptional activity in human HEK293T cells, thereby contributing to compensatory proliferation and tumorigenesis. Given its elevated expression in human colorectal cancer, ChREBP may represent a potential therapeutic target. The correlation between ChREBP-mediated Wnt signaling activation and colorectal carcinogenesis would provide deeper insights into the link between metabolic dysfunction and colorectal cancer.

overall_design: RNA-seq profiling of distal colon tissues from wildtype and ChREBP KO mice (n=3 per group) at Day17 of AOM/DSS treatment.

first: Wenrui

last: He

first: Guoxiao

last: Ji

first: Xuemei

last: Tong

first: Jian

last: Meng

first: Lifang

last: Wu


title: Dietary omega-6 lipids promote post-injury aberrant bone formation in obesity

city: Dallas

first: Sneha

last: Korlakunta

state: TX

address: 6000 Harry Hines Blvd

department: Surgery

institute: UT Southwestern Medical Center

summary: Obesity is associated with impaired wound healing, but the mechanisms linking excess adiposity to aberrant tissue repair remain unresolved. Heterotopic ossification (HO) is a severe example of pathologic tissue repair in which mesenchymal progenitor cells (MPCs) undergo aberrant osteochondral differentiation within soft tissue, leading to joint contractures and pain. Here, we show that injury site accumulation of dietary omega-6 (ω-6) lipids is a key mechanism linking obesity to heterotopic ossification. Specifically, in mice fed a high-fat diet (HFD), injured tissues are enriched in linoleic and arachidonic acids, providing substrate for myeloid cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production. PGE2 then drives a transcriptional program in mesenchymal progenitor cells that promotes osteochondral differentiation. An isocaloric, low linoleic acid HFD reduces HO despite comparable obesity, demonstrating that dietary lipid composition, rather than adiposity alone, drives pathological repair. Clinical data mirror these findings, showing that obesity confers increased HO risk, and COX-2 inhibition reduces HO exclusively in obese patients. Together, these findings identify injury site ω-6 lipid enrichment as the key signal linking the diet to MPC reprogramming, pointing to dietary lipid modulation as an actionable strategy to limit HO in obesity.

overall_design: scRNA-seq of cells isolated from the injury site at 0, 3, and 7 days after B/T injury was performed on C57BL/6 mice maintained on a high-fat diet, along with age-matched C57BL/6 high-fat diet controls, following previously published protocols.

first: Stephanie

last: Moye

first: Benjamin

last: Levi


title: MAIT cells at different developmental stages egress the thymus to colonize specific tissues and sense increases in peripheral ligands

city: PARIS

first: Anne-laure

last: Le gac

address: 26 rue d'ulm

country: France

institute: Institut Curie

summary: MAIT but not iNKT cells can be selected by thymic epithelial cells, while both require CD4+CD8+ thymocytes for maturation. MAIT and iNKT cells have similar developmental dynamics and thymic-residency properties but proliferate at different developmental stages.MAIT cells exit the thymus in an S1PR-dependent manner at different maturation stages to colonize specific peripheral organs.PLZF+Tbet-RORgt- MAIT cells preferentially colonize the intestine in a CCR9-dependent manner.Thymic output contributes to peripheral MAIT and iNKT cell numbers at steady state. Thymic MAIT17 cells are activated and expand in colitis and after bacterial exposure.

overall_design: For Thy_FTY dataset bone marrow chimeras were generated (WT into MR1KO) and, after 7 weeks, treated with Vehicle or FTY720 for 1 week. For Thy_Mr1fl, MR1fl, Foxn1-cre+Mr1fl, Vav1-icre+Mr1fl and Cd11c-creMr1fl mice were analysed. In both case thymi were mechanically dissociated, MAIT cell were magenicatically enriched with MR1:5-OP-RU-PE tetramer and anti-PE beads and total MAIT cells (Tcrblo/+ and tetramer+) were FACS sorted.

first: Rafael

last: Almeida Paiva

first: Hugues

last: Briere

first: Anne-Laure

last: Le Gac

first: Aurélie

last: Darbois

first: Laetitia

last: Perrin

first: Anya

last: Belmellat

first: Chaimae

last: Saji

first: Mariela

last: Furstenheim

first: Lea

last: Guyonnet

first: François

last: Legoux

first: Bernard

last: Malissen

first: Marion

last: Salou

first: Olivier

last: Lantz


title: Orientia tsutsugamushi Ank effectors target lamin A and chromatin to inhibit NF-kB

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: Intracellular pathogens inhibit nuclear factor-κB (NF-κB), the key transcriptional regulator of antimicrobial responses, using incompletely defined mechanisms. NF-κB nuclear localization and gene accessibility is mediated by Ser22-phosphorylated lamin A/C (pSer22-lamin A/C). Here, we report that the obligate intracellular bacterium Orientia tsutsugamushi impairs NF-κB nuclear accumulation by targeting lamin A using a cohort of ankyrin repeat (AR)-containing effectors (Anks) that have a PRANC (pox proteins repeats of ankyrin C-terminal) domain. The Anks’ immunomodulatory capability relies on a hydrophilic peptide that binds lamin A and pSer22-lamin A. Positioning of this peptide in an a-helix between the AR and PRANC domains is functionally essential. O. tsutsugamushi and ectopically expressed Ank1, one of the NF-κB-inhibiting Anks, promote pSer22-lamin A localization to the nucleoplasm. Orientia also alters chromatin to a primarily closed state to limit accessibility at many sites including those regulated by lamin A/pSer22-lamin A along with NF-κB and its coactivator, adapter protein 1. Thus, O. tsutsugamushi synergistically modulates lamin A and chromatin accessibility to counteract NF-κB. These findings reveal a strategy by which an intracellular microbe subverts host immunity, reinforces the regulatory link between lamin A and NF-κB, and indicates that pSer22-lamin A activates NF-κB by increasing chromatin accessibility to it and its coactivators.

overall_design: ATAC-seq profiling of uninfected HeLa cells and HeLa cells infected with O. tsutsugamushi at 72 hours post infection.

first: Thomas

middle: E

last: Siff

first: Paige

last: Allen

first: Haley

last: Adcox

first: Svetlana

last: Blinova

first: Travis

middle: J

last: Chiarelli

first: Jason

middle: R

last: Hunt

first: Joseph

last: Wang

first: David

middle: L

last: Armistead

first: John

middle: S

last: Billingsley

first: Nathaniel

last: O'Bier

first: Richard

middle: T

last: Marconi

first: Andrew

last: Ottens

middle: A

last: Carlyon


title: ATF7ip inhibits the tumor immune response by promoting terminal CD8+ T cell Exhaustion

city: San Francisco

first: Jun Hyung

last: Sin

state: CA

address: 513 Parnassus Ave S-1076

department: Pediatrics

institute: University of California, San Francisco

summary: CD8+ T cell exhaustion limits the immune response to tumors because of ineffective T cell effector functions. Thus, therapies that inhibit T-cell exhaustion are critical for optimizing cancer treatment. Recent studies have implicated epigenetic proteins in T-cell exhaustion. Here, we identified activating transcription factor 7 interacting protein (ATF7ip) as an epigenetic protein critical for inducing T cell exhaustion. Loss of Atf7ip in CD8+ T cells results in decreased terminal exhaustion and increased numbers of progenitor-exhausted cells in both chronic viral infections and cancer. Owing to decreased exhaustion, Atf7ip-deficiency in CD8+ T cells leads to an enhanced immune response to tumors. Mechanistically, ATF7ip functions to stimulate the deposition of repressive H3K9me3 at critical immune-effector gene loci, such as Il7r and Il2 leading to enhanced exhaustion. Our data suggest that ATF7ip may be a rational target for deletion in adoptive T-cell therapies to reduce CD8+ T-cell exhaustion.

overall_design: TCRb+CD3+ T cells from 3-4 Atf7ip-sufficient and Atf7ip-deficient mice were pooled and FACS sorted into 1.5 ml tubes containing DMEM with 2 FBS. About 20,000 cells per 100 ul were sent out for 10X sequencing. Single cells were captured using the 10X chromium microfluidics system and barcoded and sequenced on the Illumina NovaSeq.

first: Sujit

last: Kashyap

first: Michael

last: Waterfield


title: Mapping CCR4-NOT recruitment elements at high resolution reveals transcriptome-wide determinants of mRNA decay

city: Montreal

first: Marc

last: Fabian

state: Quebec

address: 3755 Côte Ste-Catherine Road

department: Department of Oncology

country: Canada

institute: McGill

type: Non-coding RNA profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Microsomal triglyceride transfer protein restricts progesterone production in Leydig Cells by regulating SREBP2 activity [ATAC-Seq]

city: Mineola

first: M. Mahmood

last: Hussain

state: New York

address: 101 Mineola Blvd.

department: Foundations of Medicine

institute: NYU Grossman Long Island School of Medicine

summary: Reduced serum testosterone or hypogonadism diminishes bone density, muscle mass, and sexual functions and increases obesity and CVD. Microsomal triglyceride transfer protein (MTP) is a lipid-transfer protein, primarily expressed in the liver and intestine, and is critical for apoB-containing lipoprotein assembly and secretion. MTP mRNA has been reported in the testis, but its function is unknown. Here, we report that MTP protein is present in the Leydig cells of human and mouse testes and plays a regulatory role in cholesterol metabolism and sex hormone production. Inhibition of the MTP activity by a specific inhibitor, knockdown, and gene ablation significantly increased progesterone secretion in mouse Leydig MA10 cells after stimulation with cyclic AMP. Molecular studies revealed that MTP enhanced the expression of genes in the uptake of lipoproteins, and in the synthesis and intracellular trafficking of cholesterol. Moreover, it enhanced the Lhcgr signaling as well as the expression of genes in the biosynthesis of progesterone. Transcriptome analysis confirmed increased expression of cholesterol and steroid biosynthesis pathways in MTP deficient clones. To understand how MTP deficiency increases expression of genes in cholesterol and steroid biosynthesis, we looked for changes in transcription factors. MTP deficiency enhanced the expression and activity of Srebp2. ATAC sequencing revealed enhanced binding of Srebp2 to the promoters of several enzymes in the biosynthesis of cholesterol and sex hormones. Furthermore, cholesterol and progesterone biosynthesis pathways were significantly attenuated after Srebp2 knockdown in MTP-deficient cells to the levels seen in wildtype cells. In short, these studies showed that MTP regulates cholesterol and steroid biosynthesis in Leydig cells by modulating the activity of Srebp2. Inhibition of testicular MTP might be useful to treat hypogonadism in some patients.

overall_design: RNA sequencing of 48h old culture of wildtype and MTP knockout MA10 cells after stimulation with 8-BrcAMP for 3h for steroidogenesis

first: Atrayee

last: Chattopadhyay

first: Tirumalasetty

last: Munichandra

last: Palaia

first: Bhargavi

last: Gangula

first: Qing

last: Miao

first: Jacques

last: Tremblay

first: Mahmood

middle: M


title: Mapping CCR4-NOT recruitment elements at high resolution reveals transcriptome-wide determinants of mRNA decay [miRNA-Seq]

summary: The CCR4-NOT complex is a central regulator of gene expression, orchestrating mRNA destabilization and decay through interactions with RNA-binding proteins (RBPs) and the miRNA-induced silencing complex (miRISC). However, identifying which RBP and miRNA target sites actively recruit this complex to engender mRNA turnover remains challenging, due in part to the multiple modes by which the CCR4-NOT can be recruited to targets. Here, to address this, we developed TRACER (Targeted RNA Association of CCR4-NOT and  Element Recovery), a crosslinking approach that enables high-throughput mapping of cis-acting RNA elements that recruit the CCR4-NOT complex to target RNAs. TRACER analysis of a human epithelial cell line uncovers thousands of CCR4-NOT target elements, including many of which map to known and/or predicted RBP binding motifs, as well as miRNA target sites. Importantly, we show that CCR4-NOT recruitment elements identified by TRACER play important roles in promoting mRNA decay. Taken together, our approach provides the first high-resolution transcriptome-wide map of CCR4-NOT targeting elements in human cells that engender mRNA decay.

overall_design: miRNA-seq of HEK293 cells to identify cis-acting RNA elements that associate with the CCR4-NOT complex

first: Zijun

last: Luo

first: William

last: Brothers

first: Aldo

last: Hernandez-Corchado

first: Justin

last: Zhao

first: Zara

last: Aryampour

first: Connor

last: Campbell-Smith

first: Hamed

last: Najafabadi


title: Microsomal triglyceride transfer protein restricts progesterone production in Leydig Cells by regulating SREBP2 activity [RNA-Seq]

overall_design: RNA sequencing of 48h old culture of wildtype and MTP knockout MA10 cells after stimulation with 8-BrcAMP for 3h

first: Thomas


title: Soluble uric acid suppresses neutrophil-mediated host defense in sepsis

city: Munich

first: Qiubo

last: Li

country: Germany

institute: LMU Klinikum

summary: Neutrophils play a critical role in host defense and sterile inflammation. However, neutrophil dysfunction is a hallmark of the acquired immunodeficiency in kidney disease, contributing to an increased susceptibility to infections such as peritonitis, sepsis, and pneumonia. We speculated that the impaired renal clearance of the metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-14 mg/dL) related or unrelated to kidney disease significantly exacerbated the inflammatory immune response to infection by impairing neutrophil dynamics and functions in mice with mono- and polybacterial sepsis. This aggravated inflammatory response was partially reversible by lowering UA levels with febuxostat. We validated these findings in vitro using either neutrophils or serum from healthy individuals or hyperuricemic patients with chronic kidney disease. Depleting UA partially restored neutrophil dysfunction. Mechanistically, sUA impaired the phagocytic capability, bacterial clearance, and oxidative burst in neutrophils by modulating cytoskeletal dynamics and promoting degranulation, processes essential for host defense. In contrast, sUA had no impact on neutrophil extracellular trap formation in neutrophils from healthy subjects exposed to LPS or E.coli. Our findings identify HU related or unrelated to kidney disease as immune regulator in exacerbating the inflammatory response during sepsis, primarily by impairing neutrophil-mediated phagocytosis, pathogen clearance, and oxidative burst. Targeting UA may help to overcome the acquired immunodeficiency during infection, while aggravating sterile forms of inflammation.

overall_design: Human peripheral blood neutrophils were isolated and subjected to different stimulations, including LPS, soluble uric acid (sUA), and fMLP, either individually or in combination. RNA sequencing was performed to investigate the transcriptional responses of neutrophils under these conditions.

first: Juliane

last: Anders

first: Kailey

last: Flora

first: Fengjun

last: Zhang

first: Oliver

last: Soehnlein

first: Stefanie

last: Steiger


title: Mapping CCR4-NOT recruitment elements at high resolution reveals transcriptome-wide determinants of mRNA decay [RIP-Seq]

first: Marc

last: Fabian

overall_design: RIP-seq of HEK293 to capture CCR4-NOT-associated RNAs by immunoprecipitation with V5-tagged CNOT7 subunit harboring a D40A mutation to impair catalytic activity of the complex.


title: Transcriptome sequencing of Hodgkin lymphoma Hodgkin and Reed-Sternberg cells reveals escape from NK cell recognition and an unfolded protein response

city: New York

first: Isabella

last: Kong

address: 1300 York Ave

institute: Weill Cornell Medicine

summary: The mutational profile of classic Hodgkin lymphoma (cHL) overlaps with that of related B cell lymphomas, including primary mediastinal B cell lymphoma (PMBL), and yet these are different histologically and clinically. To discover the molecular features that distinguish cHL, we deployed flow cytometric cell sorting and low-input RNA sequencing to generate full transcriptome data from viable, isolated Hodgkin and Red-Sternberg (HRS) cells from eighteen primary tumors, alongside matched intra-tumoral non-neoplastic B cells and four cell lines.  Comparison of HRS cells to normal cellular subsets revealed evidence of abortive plasma cell differentiation, with an unfolded protein response signature, shared with plasma cell neoplasms, but not other B-cell lymphoma types. Comparison of cHL to PMBL revealed similarities but also key differences in B cell differentiation programs accompanied by upregulation of genes involved in microtubule cytoskeleton organization in cHL, which may be related to the unique multinucleated nature of HRS cells. In HRS cells, we also observed a downregulation of SLAM family receptors, which are crucial for NK cell activation, providing a potential mechanism for immune evasion from NK-mediated killing. New fusion transcripts were seen, including a recurrent transcript predicted to result in an in-frame fusion protein involving TRAF1 and PHF19.

overall_design: Bulk RNA-seq profiling the transcriptome differences between HRS cells and intra-tumoral B cells following flow-cytometry sorting.

first: Mikhail

last: Roshal

middle: Y

first: Wikum

last: Dinalankara

first: Lisa

last: Giulino-Roth

first: Ethel

last: Cesarman


title: H3K9me3 controls epidermis development by repressing RNA Pol II initiation on key promoters and enhancers [scRNA-seq]

first: Chris

last: Bai

overall_design: Suv39h1,SUv39h2,Setdb1 triple knockout was induced in embryonic basal cells to deplete H3K9me3 and then single cell RNA-seq profiling was performed on sorted Epcam+α6+ double positive basal cells at E16.5

first: Tudorita

last: Tumbar


title: H3K9me3 controls epidermis development by repressing RNA Pol II initiation on key promoters and enhancers [PReCISseq]

overall_design: K14Cre+,Suv39h1 f/f, Suv39h2 -/-,Setdb1 f/f triple knockout line was crossed to Polr2b-GFP f/f line to tag RNA Pol II specifically in skin epithelium. PReCIS-seq was then performed on dissected embryo dorsal skin. Embryos heterozygous for Suv39h1, Suv39h2, Setdb1 were used for control. PReCIS-seq was performed following steps described in original paper.


title: H3K9me3 controls epidermis development by repressing RNA Pol II activity on key promoters and enhancers [bulk RNA-Seq]

overall_design: Suv39h1,SUv39h2,Setdb1 triple knockout was induced in embryonic basal cells to deplete H3K9me3 and then bulk RNA-seq profiling was performed on sorted Epcam+α6+ double positive basal cells at E16.5


title: H3K9me3 controls epidermis development by repressing RNA Pol II activity on key promoters and enhancers [CUT&Run]

overall_design: Suv39h1,SUv39h2,Setdb1 triple knockout was induced in embryonic basal cells to deplete H3K9me3 and then CUT&RUN was performed on sorted Epcam+α6+ double positive basal cells at E15.5, using H3K9me3 antibodies and IgG as control


title: Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation [RNA-seq]

city: Kunming

first: Liangliang

last: Wang

state: Yunnan

address: South Section, East Outer Ring Road, Chenggong District

institute: Yunnan University

summary: Zygotic genome activation (ZGA) marks the first transcriptional milestone and establishes embryonic totipotency. Although pioneer factors have been reported to initiate this process, how chromatin is primed for the totipotent state, allowing the binding of pioneer factors for successful ZGA, remains unclear. Here, we identify IntS11, the catalytic subunit of the Integrator complex, as a totipotent determinant of embryonic chromatin governing ZGA in Drosophila. We show that IntS11 functions upstream of pioneer factors in early embryos: maternal IntS11 depletion substantially impairs RNA polymerase II (Pol II) recruitment, thereby preventing pioneer factors Zelda and GAGA factor (GAF) from accessing regulatory elements and initiating genome-wide zygotic transcription. Mechanistically, IntS11 exerts dual roles: its canonical endonuclease activity is required to sustain major-wave zygotic transcription, while a distinct enzyme-independent function drives de novo Pol II loading and pioneer factor engagement. These findings uncover a fundamental maternal-specific mechanism whereby IntS11 establishes transcriptional competence, ensuring totipotent chromatin states and successful ZGA.

overall_design: To investigate the effect of IntS11 on the zygotic gene activation of drosophila embryo, we established a variety of mutants. We then performed gene expression profiling analysis using data from RNA-seq of mutant embryos and wild-type embryos at 2-3 time points.

first: Yiru

first: Yaqi

last: Miao

first: Yuan

last: Song

first: Jialiang

last: Zhou

first: Yuanxiang

last: Zhu

first: Ying

last: Cheng

first: Wenxin

first: Qinmiao

last: Sun

first: Fan

last: Lai

first: Guoqiang

first: Dahua

last: Chen


title: Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation [Micro-C]

overall_design: To investigate the effects of IntS11 on Drosophila embryos, we generated various mutants. Subsequently, we performed Micro-C analysis using both mutant and wild-type embryos.

last: Zhang


title: Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation [ChIP-seq]

overall_design: To investigate the role of IntS11 in Drosophila embryos, we generated multiple mutant lines. Subsequently, we performed ChIP-seq analyses with multiple antibodies using both mutant and wild-type embryos.


title: SIRT6 Overexpression Counteracts Chromatin Aging

city: Baltimore

first: Supriyo

last: De

state: Maryland

address: 251 Bayview Blvd

department: Laboratory of Genetics and Genomics

institute: NIA-IRP, NIH

type: Methylation profiling by high throughput sequencing

summary: Aging is associated with detrimental changes in chromatin structure and gene expression, contributing to inflammation, metabolic decline and tissue dysfunction. SIRT6, a histone deacetylase, plays a key role in maintaining chromatin integrity and promoting longevity. Here, we show that aging leads to increased chromatin accessibility in the murine liver, accompanied by upregulation of inflammation and downregulation of metabolic pathways. Remarkably, SIRT6 overexpression reversed these changes, reducing inflammation and enhancing metabolic function. Notably, ETS family members were enriched in regions with increased accessibility during aging, while liver-enriched transcription factors (LETFs) were enriched in regions with reduced accessibility. ChIP-seq analyses of H3K9ac and H3K56ac binding showed that H3K9ac, but not H3K56ac, is associated with increased accessibility during aging, and that SIRT6 can reverse this effect. Furthermore, AAV-mediated SIRT6 overexpression in aged mice demonstrated that SIRT6 not only slows age-related chromatin changes but can also reverse them, rejuvenating chromatin accessibility to a youthful state.

overall_design: Methylome of liver from WT and SIRT6 tg, young (3-4 mo) and old (23-24 mo) mice

first: Ron

last: Nagar

first: Zacharia

last: Scwartz

first: Haim

last: Cohen


title: Gene expression analysis of Subperitoneal Fibroblast (SPF) by knockdown of Transgelin.

city: Kashiwa-shi

first: Okamoto

last: Ryuji

address: 6-5-1 Kashiwanoha

country: Japan

institute: National cancer center east

summary: Transgelin expression in colorectal cancer has been reported to correlate with patient prognosis. The aim of this study was to investigate the function of Transgelin in fibroblasts of colorectal cancer. As a method, we assessed whether knockdown of Transgelin alters the expression of the gene.

overall_design: Gene expression analysis of SPF was performed by RNA sequence. Three SPFs, each established from separate cancer tissue samples, were transfected with sh luc or sh Transgelin#1. After introduction of the sh vector, RNA derived from stimulated and unstimulated cells was extracted by addition of cancer cell culture supernatant. The final analysis was performed using 3 (SPF type) × 2 (2 vectors) × 2 (with or without cancer cell culture supernatant added) for a total of 12 Samples.


title: Bile acids mediate liver-bone marrow crosstalk

status: Public on Apr 12 2026

city: Westmead

first: Brian

last: Gloss

state: NSW

address: 176 Hawkesbury Rd

department: Scientific Platforms

country: Australia

institute: Westmead Institute of Medical Research

summary: This study examines the impact of tumor presence on bone marrow hematopoiesis in mouse models of liver cancer. Using a Hepa1-6 xenograft model in C57BL/6 mice, hematopoietic stem and progenitor cell populations were analyzed by flow cytometry. Although overall HSPC frequencies did not differ between tumor-bearing and control mice, tumor size positively correlated with HSPC numbers. RNA-seq comparison between xenograft and DEN-induced liver tumors revealed distinct transcriptomic profiles, indicating that xenograft tumors do not fully recapitulate the liver tumor microenvironment.

overall_design: Hepa1-6 mouse hepatoma cells were cultured in DMEM supplemented with 10% FBS, penicillin-streptomycin, and GlutaMAX. Cells were resuspended at 1×10⁷ cells/mL, mixed 1:1 with growth factor-reduced Matrigel, and 1×10⁶ cells were injected subcutaneously into the flanks of 6–8-week-old C57BL/6 mice. Tumors were harvested after 4 weeks or when tumor weight reached ~1 g.

first: Esmaili

last: Saeed


title: Maternal IntS11 primes embryonic totipotency by organizing early zygotic transcription initiation [ATAC-seq]

first: Liangliang

last: Wang

overall_design: To investigate the role of IntS11 in Drosophila embryos, we generated multiple mutant lines. Subsequently, we performed ATAC-seq analyses using both mutant and wild-type embryos.

first: Yiru

first: Yaqi


title: Low inflammation correlates with protumor Tim4+ TREM1+ resident macrophage expansion and limited monocyte-derived macrophage formation during peritoneal colorectal cancer

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

institute: CNB, CSIC

summary: Research based essentially on mouse models of ovarian cancer peritoneal metastasis have revealed that peritoneal macrophages, that include resident peritoneal macrophages (resMØs) and monocyte-derived non-resident macrophages, promote peritoneal tumor growth, through the induction of tumor cell proliferation and migration, and immunosuppression. However, the mechanisms controlling the expansion and differential contribution of resMØs and monocyte-derived non-resident macrophages to the pool of peritoneal macrophages present in tumor-bearing mice, and to promote tumor growth, remains to be addressed. Using a mouse model of colorectal cancer (CRC) peritoneal metastasis, based on the intraperitoneal injection of mouse tumor organoids, derived from primary tumors arising in genetically engineered mice, bearing mutations in Apc, Kras, Tgfbr2 and Trp53,  and developing human-like metastatic CRC tumor growth, in the present report, the origin, expansion and function of peritoneal macrophages during peritoneal CRC tumor growth, has been investigated. Our data support that the low inflammatory status of the peritoneal cavity associated to CRC peritoneal tumor growth, restrained Ly6Chi monocyte recruitment and formation of Tim4- resMØs and moMØs, while enabling a marked cell proliferation-driven expansion of Tim4+ resMØs. Tumor-induced Tim4+ resMØs displayed a migratory and protumor transcriptomic signature, involving the activation of genes controlling the expression of important protumor molecules, such as A2A/A2B, ARG1, IDO, IL-6, IRG1, MMP12, PD-L1/2, SPP1, TREM1 and VEGFa. Correspondingly, during peritoneal CRC tumor growth, Tim4+ TREM1+ resMØs migrated to the omentum, the main peritoneal target organ for peritoneal metastasis, and promoted CRC peritoneal tumor progression.

overall_design: RNA-seq profiling of Tim4+ resident macrophages isolated from peritoneal fluid in steady state (Ctrl x3 replicates) and 12 days after MTO injection (12d x4 replicates)

first: Margarita

last: Ferriz

first: Natalia

last: Álvarez-Ladrón

first: Alejandra

last: Gutiérrez-González

first: Marta

last: H. Fernández-Sesma

first: Adrián

last: Vega-Pérez

middle: C

first: Ana

last: Cayuela López

first: Eduard

last: Batlle

first: Daniele

last: Tauriello

first: Carlos

last: Ardavín


title: Higher basal tumor immune activity coupled with a systemic immune response improves liver cancer outcomes

summary: This study examines how systemic immune responses and liver immune activity influence liver tumor development. In a diethylnitrosamine (DEN)‑induced mouse model of hepatocellular carcinoma, mice were fed different diets for 26 weeks to assess the impact of metabolic and inflammatory conditions on tumor progression. Tumor burden varied across diets, with increased tumor formation in some diets and a diet with combined cholesterol and cholic acid showing tumor burdens similar to controls. Flow cytometry revealed that mice on the combined diet exhibited the strongest expansion and activation of bone marrow hematopoietic stem and progenitor cells (HSPCs). RNA‑seq was performed on tumor and non‑tumor liver tissues to profile diet‑associated transcriptional changes, and weighted gene co‑expression network analysis (WGCNA) identified conserved immune‑related gene expression modules. Enhanced systemic hematopoietic responses were associated with stronger liver immune gene expression and increased innate immune cell infiltration, correlating with reduced tumor burden. These findings highlight a link between systemic hematopoietic activation, hepatic immune responses, and liver tumor outcomes.

overall_design: Male C57BL/6 mice were injected intraperitoneally with 25 mg/kg body weight of diethylnitrosamine (DEN) at 14 days of age. These mice were then given the diets containing 34% Sucrose (HS diet), cholic acid (0.5%) added diet (CA diet), or a cholesterol rich diet (2%) which contained high sucrose (34%), 2% cholesterol and 0.5% cholic acid (ChR diet) starting from week 22 for 14 weeks. The control group was fed with the normal chow (NC) diet throughout the experiment. The mice were harvested at 34 weeks after injection (at the age of 36 weeks).


title: The role of PurR purine transcriptional repressor and Rae1 endoribonuclease in Erm-mediated macrolide resistance in methicilin-resistant Staphylococcus aureus.

city: Chicago

first: Mee-Ngan

middle: F.

last: Yap

state: IL

address: 320 E Superior St

department: Microbiology-Immunology

institute: Northwestern University Feinberg School of Medicine

summary: Differential gene expression between six S. aureus strains were determined by RNA-seq in 3 biological replicates.The six strains are ermB_minus parental JE2(WT), ermB_proficient strain (KES29), ermB_minus rae1 mutant (MNY205), ermB_proficient rae1 mutant (MNY212), ermB_minus purR mutant (MNY221), and ermB_proficient purR mutant (MNY224). Two culture media were used: A indicates tryptic soy broth (TSB), B indicates RPMI_1640 supplemented with 1% casamino acids.

overall_design: Investigate how inactivation of purR and rae1 in Staphylococcus aureus promotes macrolide resistance.

first: Alexandre

last: Le Scornet

middle: F


title: Gene expression in Erm-minus and Erm-proficient Staphylococcus aureus strains under sublethal and lethal doses of erythromycin

summary: Differential gene expression between five S. aureus strains were determined by RNA-seq. The five strains are ermB_minus parental JE2(WT), ermB_proficient strain (ALS77),  ermB_proficient delta_rae1 mutant (ALS101), ermB_minus delta_purR mutant (MNY221), and ermB_proficient delta_purR mutant (ALS97).

overall_design: Investigate how inactivation of purR and rae1 in Staphylococcus aureus promotes macrolide resistance with and without erythromycin exposure

first: Jonathan

last: Winkelman


title: High-resolution spatial transcriptomics of mouse intestine [Spatial-RNAseq]

city: Hangzhou

first: Li

last: Li

state: Zhejiang

address: Shilongshan ST #18, Xihu District

institute: Westlake University

summary: Spatially-resolved single-cell lineage tracing is a powerful approach for studying cell lineages and fate decisions in situ. However, existing studies are limited to specific cell types such as lymphocytes and cancer cells. We recently developed DARLIN, a lineage tracing mouse model that has massive lineage barcodes and efficient barcode recovery. Here, we present Spatio-DARLIN, a generic spatial lineage tracing tool that integrates sequencing-based spatial transcriptomics with DALRIN mouse. Applying it to the small intestine, we observed a high-quality transcriptome with nearly single-cell resolution and recovered ~25% cells with reliable lineage barcodes, resulting in ~7000 clones with >1 cell per tissue section. These clones showed highly reproducible spatial localization across adjacent tissue sections, confirming their accuracy. With this high-throughput approach, we observed that intestinal epithelial clones were localized along the crypt-villus axis and underwent vertical expansion over a longer tracing period. Since DARLIN is publicly available and labels cells across most tissues, Spatio-DARLIN offers an accessible and efficient approach for spatial lineage tracing across various mouse tissues with high resolution.

overall_design:
DARLIN mice were generated by crossing homozygous Col1a1tetO-Cas9?TdT-gRNAs:Rosa26M2-rtTA mice with Col1a1CA:TigreTA:Rosa26RA mice, which were maintained separately.
For the proof-of-concept experiment, one 8-week-old DARLIN mouse was administered doxycycline (Dox) for one week, and the proximal small intestine was collected one week after Dox induction.
For the time-course experiment, two 4-week-old DARLIN mice were treated with Dox for one week, and proximal small intestines were collected at 2 and 3 weeks after Dox induction, respectively.
For the clone verification experiment, one 8-week-old DARLIN mouse was induced with Dox for one week, and the small intestine was collected one week post-induction, then dissected into proximal, middle, and distal regions. Three adjacent tissue sections (20??m apart) from the middle region were collected for spatial transcriptomics.
For the brain development application, one E10 DARLIN mouse was induced with Dox for 12h, and the brain was collected after 8 weeks (7 weeks old) post-induction.

first: Jianing

last: Gao

first: Daolong

last: Chen

first: Zhanhao

last: Zhang

first: Shouwen


title: High-resolution spatial transcriptomics of DARLIN mouse [CRISPR array amplicon]

overall_design:
DARLIN mice were generated by crossing homozygous Col1a1tetO-Cas9–TdT-gRNAs:Rosa26M2-rtTA mice with Col1a1CA:TigreTA:Rosa26RA mice, which were maintained separately.
For the proof-of-concept experiment, one 8-week-old DARLIN mouse was administered doxycycline (Dox) for one week, and the proximal small intestine was collected one week after Dox induction.
For the time-course experiment, two 4-week-old DARLIN mice were treated with Dox for one week, and proximal small intestines were collected at 2 and 3 weeks after Dox induction, respectively.
For the clone verification experiment, one 8-week-old DARLIN mouse was induced with Dox for one week, and the small intestine was collected one week post-induction, then dissected into proximal, middle, and distal regions. Three adjacent tissue sections (20 μm apart) from the middle region were collected for spatial transcriptomics.
For the brain development application, one E10 DARLIN mouse was induced with Dox for 12h, and the brain was collected after 8 weeks (7 weeks old) post-induction.

last: Wang


title: SIRT6 Overexpression Counteracts Chromatin Aging [ATAC-Seq_tg]

city: Ramat-Gan

first: Haim

middle: Yosef

last: Cohen

address: Max & Anna Webb

country: Israel

institute: Bar-Ilan University

overall_design: ATAC-seq of liver from WT and SIRT6 tg, young (5-7 mo) and old (18-21 mo) mice

first: Ron

last: Nagar

first: Zacharia

last: Scwartz


title: SIRT6 Overexpression Counteracts Chromatin Aging [ATAC-seq]

overall_design: ATAC-seq of liver from 24 months old mice injected with AAV8 SIRT6 or GFP for hepatocyte specific expression


title: SIRT6 Overexpression Counteracts Chromatin Aging [ChIP-Seq]

overall_design: H3K9ac, H3K56ac and H3K27ac ChIP-seq of liver from WT and SIRT6 tg, young (5-7 mo) and old (18-21 mo) mice


title: Leukaemia cell intrinsic and extrinsic factors cooperate to facilitate the survival and proliferation of KMT2A-rearranged B-ALL in the CNS niche.

city: Edinburgh

first: Alasdair

last: Duguid

address: 5 Little France Drive

department: Institute for Regeneration and Repair

institute: University of Edinburgh

summary: Infant B-cell acute lymphoblastic leukaemia (B-ALL) is a rare, aggressive entity characterised by KMT2A-rearrangements and poor outcomes. One of the unique features of KMT2A-rearranged infant ALL contributes to these poor outcomes is a particularly high rate of central nervous system (CNS) involvement. In this study we used an immune competent KMT2A-AFF1+ infant B-ALL murine model (https://doi.org/10.1182/blood.2020006610) to explore the cell-intrinsic and cell-extrinsic mechanisms that underpin this clinically significant complication. We show novel functional impacts on leukaemia propagating cells (LPCs) following exposure to the CNS niche which results in unique leukaemia repopulation dynamics. Transcriptomic and immune cell profiling comparisons by niche showed differences in the immune microenvironment between the CNS and bone marrow (BM) niches. We observe the CNS niche demonstrates supressed T cell and macrophage activity which may be part of a wider CNS niche-specific immune escape mechanism. Our transcriptomic comparisons by niche also led us to explore the role of PI3K pathway activation in the propagation of leukaemia cells within the CNS niche. We identify miR-93 as a possible master regulator of this process. The importance of miR-93 is emphasised as it is shown to be upregulated in CNS leukaemia cells across multiple murine KMT2A-AFF1 B-ALL model systems and in primary KMT2A-AFF1 B-ALL patient samples. We conclude by showing impaired CNS engraftment of leukaemia cells upon miR-93 knockdown, cementing its importance in CNS leukaemia biology.

overall_design: BM and CNS cells from miR-128a overexpression Kmt2a-AFF1+ mouse model of infant pro-B ALL, described in Malouf et al. 2021, were harvested. These cells were FACS-sorted into different LPC populations (LSK-IL7R+: Lin- Sca1+ cKit+ IL7R+ and LK/CLP: Lin- Sca1- cKit+) for RNA extraction and bulk sequencing. Transcriptomic comparisons were made by LPC type and by niche.

first: Camille

last: Malouf

first: Katrin

last: Ottersbach


title: SIRT6 Overexpression Counteracts Chromatin Aging [RNA-Seq]

overall_design: RNA-seq of liver from WT and SIRT6 tg, young (5-7 mo) and old (18-21 mo) mice


title: Transcriptomic and Accessibilty characterization of Wild type mouse Embryonic Stem Cells (mESCs),  β-actin Knock out mESC and upon rescue with a nuclear localization signal  β-actin

status: Public on Apr 11 2026

city: Abu Dhabi

first: Piergiorgio

last: Percipalle

address: NYUAD Saadiyat Island

institute: Biology

summary: Pluripotency and lineage commitment in embryonic stem cells depend on coordinated regulation of chromatin architecture and extracellular matrix (ECM) signaling. Here, we identify nuclear β-actin as a key regulator linking these processes in mouse embryonic stem cells. Loss of β-actin disrupts core pluripotency factors, including Oct4 and Sox2, and causes broad transcriptional changes, while nuclear re-expression rescues these defects. Chromatin accessibility analysis revealed reduced accessibility at regulatory regions of pluripotency genes, consistent with impaired chromatin remodeling. β-actin depletion also altered ECM-related gene expression, matrix properties, and cellular biomechanics, leading to impaired self-renewal, skewed lineage specification, and defective differentiation, particularly reduced neuronal potential and increased mesodermal-like fate bias. In vivo, β-actin loss restricted teratoma growth and compromised tri-lineage differentiation. Together, these results define nuclear β-actin as an important regulator of chromatin accessibility, ECM-dependent signaling, and stem cell fate.

overall_design: ATAC seq of WT, beta actin KO, and NLS  for mouse Embryonic stem cells.

first: Nadine

last: Hosny El Said

first: Colin

last: Campbell

first: Amani

last: Nuairi

first: Sabrina

last: Desbordes


title: Polymicrobial extracellular vesicles reduce the innate immune response of human cystic fibrosis bronchial epithelial cells

city: Hanover

first: Lily

last: Charpentier

state: New Hampshire

address: Dewey Field Road, HB 7550

department: Microbiology and Immunology

institute: Geisel School of Medicine at Dartmouth

summary: Adults with cystic fibrosis (CF) have chronic antibiotic-resistant polymicrobial lung infections, the leading cause of death in CF. We developed a polymicrobial culture model containing four genera that represents a ‘pulmotype’ detected in ~34% of lung infections in people with CF (pwCF), and accounts for 27% of the variability in lung function. This community, comprised of Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus sanguinis, and Prevotella melaninogenica, is grown in synthetic CF media (SCFM2) under anoxic conditions that mimic the environment in mucus plugs in CF. We have shown that Pseudomonas in monoculture communicates with primary human bronchial epithelial cells (pHBEC) by secreting bacterial extracellular vesicles (bEVs) that diffuse through mucus and deliver virulence factors, DNA, and RNA to pHBEC. We report herein that each bacterial genus in the polymicrobial community secretes bEVs containing proteins and RNAs predicted to promote the establishment of chronic infection by enhancing virulence and biofilm formation, and upregulating the stress response and pro-inflammatory pathways in pHBEC. This response is most pronounced in CF pHBEC. Trikafta, a highly effective drug, does not ameliorate the response or return it to WT levels. Bacterial EVs also inhibited Trikafta-stimulated CFTR Cl- currents by CF pHBEC. These studies provide insight into why Trikafta does not eliminate polymicrobial lung infections and a hyperinflammatory lung environment in pwCF.

overall_design: RNA-seq profiling of WT and CF primary human bronchial epithelial cells treated with either polymicrobial bacterial extracellular vesicles or processed control.

first: Bruce

last: Stanton


title: Berry-derived gold nanoparticles induce integrated oxidative stress-mediated apoptosis, immune modulation, and transcriptomic remodeling in 4T1 triple-negative cancer cells

city: Wilmington

first: Oladapo

middle: Fisoye

last: Fagbohun

address: 1870 Quaker Way

department: Biology

institute: Wilmington College

summary: Comprehensive molecular and phenotypic characterization of tumor models is still needed for robust understanding of breast cancer mechanisms and therapies. Here, we explore genome, transcriptome, and proteome of treated and untreated 4T1 triple-negative breast cancer cells. Nanoencapsulation (AuNPs) of berry-derived polyphenolic compounds was influenced by limited clinical use due to poor stability and bioavailability. Several physicochemical characterizations employed include TEM, FTIR, and targeted UPLC/MS-QQQ assays. We identified significant mutations to breast cancer-related tumor suppressor genes (Trp53, Brca2, Bard1, Cdh1, Nf1, and Chek2) and deciphered the function consequences leveraging on the higher throughput Illumina NovaSeq X and NextSeq 1000 sequencers and highly accurate predicting power of AlphaFold. We found ~5700000 single nucleotide variations (SNVs) and 329448 indels achieving an important upgrade over previous literature data. Key findings from differentially expressed gene  enrichment analyses (GSEA) revealed positive gene enrichments of DNA repair regulators and TGF-β signaling while having negative enrichments of cell adhesion, cadherin and MAPK signaling via PI3K/AKT/MAPK/Wnt pathways, potentially influencing apoptosis and immune evasion intrinsic to cancer. Notably, decreased expression of PIK3CG, PALLD, PTPRZ1, and CDH8 and increased expression of SEMA6C, WWOX, NHEJ1, and MAML3 suggested suppression of epithelial-to-mesenchymal transition (EMT) and metastatic potential. Further assessment of immunohistochemical, immunofluorescent, and flow cytometric data revealed that berry-derived nanoparticles can modulate oncogenic transcription factors and induce caspase-dependent execution-phase ROS-mediated apoptosis through pPAK1Thr212 dephosphorylation, downregulation of pPI3Kp85αγ(Tyr467/199)/pAKT1Thr450/mTOR signaling, and modulation of pJAK3Tyr785/STAT3 pathway supporting transcriptomic and transcriptional reprogramming of 4T1 treated cells. Together, our findings uncover a new strategy to capture berry-derived polyphenols required to regulate apoptosis, autophagy, immune response, and metastasis-related gene networks in breast cancer thereby underscoring the therapeutic potential of functionalized AuNPs as delivery platforms for dietary phytochemicals.

overall_design: mRNA libraries were prepared using the flowing reagents from QIASeq FastSelect RNA Lib HMR and QIA UX96 Index UDI-B (96) 331825 Kits (Qiagen Inc., Santa Clarita, CA, USA; Cat#: 334235) with primers N6-T RT and ODT-RT. The quality of the libraries was evaluated with fluorometry by DeNovix QFX fluorometer (DeNovix Inc., Wilmington, DE, USA; S/N: S-04083) and with 2100 Bioanalyzer (Agilent Technologies Inc., Santa Clara, CA, USA; S/N: DE72903137). A total of 100 ng total RNA was used for the sequencing. Ribosomal RNA was removed by enzymatic digestion and then fragmented for 3 min. The libraries were sequenced with Illumina NovaSeq X plus 10B (Illumina Inc., San Diego, CA, USA), with sequence coverage ranging between PF clusters 35 million to 50 million paired reads. Raw data were converted into FASTQ format, demultiplexed, and filtered for reads passing QC filters. Adapter and low-quality sequences were trimmed and only sequences with Q30 or higher quality were used. RNA Seq FASTQ files were processed and mapped to reference. RNA sequencing reads were aligned to the published Mus musculus reference genome. Mapping rates and coverage statistics of the samples were reported.

first: Adewale

last: Oladipo

first: Chengyu

last: Gao

first: Babatunde

last: Olawoye

first: Rachel

last: Berry

first: Jaylah

last: Captain

first: Olive

last: Iragena

first: Xavier

last: McDougle

first: Randy

last: Harris

first: Amanda

last: Rollins

first: Jitcy

last: Joseph

first: Olatomide

last: Fadare

first: Russell

last: Kincaid


title: Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis

city: Chiang Mai, Thailand

first: Ranchana

last: Yeewa

state: State/Province

address: Faculty of Medicine, Chiang Mai University 110 Intawaroros Road, Si Phum, Muang, Chiang Mai

country: Thailand

institute: Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University

summary: YEATS2, a chromatin-associated factor, is essential for maintaining dopaminergic (DA) synaptic integrity, but the underlying mechanism remains unclear. Using Drosophila, we show that neuronal depletion of YEATS2 alters brain transcriptomes, downregulating metabolic genes and upregulating G protein–coupled receptors (GPCRs). This correlates with elevated intracellular calcium levels, leading to neurobehavioral deficits and selective DA neuron loss. Crucially, genetic or pharmacological inhibition of the store-operated calcium entry channel Orai restores calcium balance and rescues DA neuron survival. These findings reveal a YEATS2-dependent epigenetic–calcium axis critical for dopaminergic neuron vulnerability.

overall_design: RNA-seq profiling of heads of nSyb>mCherry IR (NTC IR-1), nSyb>dYEATS2 IR (dYEATS2-IR), nSyb>Luciferase IR (NTC IR-2), and nSyb>dENL/AF9 IR (dENL/AF9 IR) at 3-day-old.

first: Luca

last: Lo Piccolo

first: Pitiporn

last: Noisagul

first: Arnaud

last: Monteil

first: Vorasuk

last: Shotelersuk

first: Salinee

last: Jantrapirom


first: Lily

last: Charpentier

sample_organism: Staphylococcus aureus subsp. aureus str. Newman

overall_design: RNA-seq profiling of bacterial extracellular vesicles from a polymicrobial culture containing Pseudomonas aeruginosa PA14, Staphylococcus aureus Newman, Streptococcus sanguinis SK36, and Prevotella melaninogenica ATCC 25845.

first: Bruce

last: Stanton


title: Longitudinal multi-organ transcriptomic atlas of salt-induced hypertension

city: Tampa

first: Ratnakar

last: Tiwari

state: FL

address: 560 Channelside Dr

department: Molecular Pharmacology & Physiology

institute: University of South Florida

summary: Salt-sensitive hypertension is a common form of hypertension characterized by an exaggerated blood pressure response to dietary salt intake. The molecular mechanisms linking salt-induced hypertension to multi-organ damage remain poorly defined. To address this issue, we generated a longitudinal multi-organ transcriptomic atlas by performing RNA sequencing on the kidney cortex, kidney medulla, liver, and heart across four stages of hypertension in male Dahl salt-sensitive rats. These data provide a valuable resource for identifying organ-specific transcriptional responses involved in the pathogenesis of salt-induced hypertension.

overall_design: Animals were maintained on a normal-salt diet (0.4% NaCl, #D113755, Dyets Inc.). To induce hypertension, 9- to 11-week-old male Dahl salt-sensitive rats were switched to a high-salt diet (4% NaCl, #D113756, Dyets Inc.) for 7, 14, 21, or 35 days. Multiple tissues were collected at each time point, and extracted RNA was used for sequencing and downstream analysis.

first: Alexander

last: Staruschenko


title: Cyclin-dependent kinase-9 and oxidative phosphorylation inhibition overcome ibrutinib resistance in mantle cell lymphoma

status: Public on Apr 10 2026

city: Portland

first: Zheng

last: Xia

state: Oregon

address: 2720 S Moody Ave

department: Department of Biology Medical Engineering

institute: Oregon Health Science University

summary: Resistance to Bruton tyrosine kinase inhibitors (BTKi) is inevitable in mantle cell lymphoma (MCL). Cyclin-dependent kinase-9 (CDK9), a key regulator of oncogenic transcription, is a promising therapeutic target. Here we studied a selective CDK9 inhibitor, AZD4573, in MCL. AZD4573 suppressed growth of MCL cell lines and primary cells and reduced expression of key oncogenic programs including MYC and MCL1. However, CDK9 inhibition also induced metabolic adaptation, with increased oxidative phosphorylation (OxPhos), ATP production, and reactive oxygen species in ibrutinib-resistant models. In an ibrutinib-resistant MCL PDX model, AZD4573 produced modest survival benefit and suppressed TNFα/NF-κB and mTORC1 signaling, but OxPhos remained elevated. To define treatment-associated transcriptional changes at cellular resolution, we analyzed PBMCs from patients receiving AZD4573 using single-cell RNA sequencing. In a responding MCL patient, malignant B cells showed sustained downregulation of MYC targets and OxPhos, whereas refractory patients showed the opposite pattern, with upregulation of MYC-associated and OxPhos programs. Consistent with these findings, the OxPhos inhibitor IACS-010759 synergized with AZD4573 in vitro. Together, these results support CDK9 inhibition as a therapeutic strategy in BTKi-resistant MCL and highlight single-cell transcriptomics as a powerful approach to reveal response-associated malignant cell states and rational combination vulnerabilities.

overall_design:
PBMCs from peripheral blood was collected from patients (AZ01 and AZ06) treated with AZD4573 at the prespecified timepoints: baseline 0 hours, 4 hours, 24 hours, and cycle 1 day 8 (C1D8). AZ01_0hr: CMO301, AZ01_4hr: CMO302, AZ01_24hr: CMO303, AZ01_C1D8: CMO304; AZ06_0hr: CMO305, AZ06_4hr: CMO306, AZ06_24hr: CMO307, AZ06_C1D8: CMO308.

***************************************************************
Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
***************************************************************

first: Carly

last: Roleder

first: Xiaofan

last: Zhao

first: Vi

last: Lam

first: Edward

last: Dominguez

first: Canping

last: Chen

first: Sonia

last: Rodgriguez-Rodriguez

first: Lili

last: Wang

first: Tycel

last: Phillips

first: Alexey

middle: V

last: Danilov


title: PP2A Regulates Senescence and Immunogenicity in Medulloblastoma

city: Memphis

first: Jiyang

last: YU

state: TN

address: 262 Danny Thomas Place

department: Department of Computational Biology

institute: St. Jude Children’s Research Hospital

summary: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Current treatments carry significant morbidity, and prognosis remains poor in subgroups with TP53 mutations or relapse, underscoring the need for new therapeutic strategies. Senescence is a tumor-suppressive program disrupted in MB. We hypothesized that restoring senescence through p53-independent mechanisms could be therapeutic. Here, we identify Protein Phosphatase 2A (PP2A) as a key regulator of senescence in MB. Genetic ablation of the PP2A catalytic subunit (PP2Ac) or knockdown of the regulatory subunit PP2A-B56α induces robust senescence in TP53-mutant MB models. Senescent PP2Ac-deficient cells show increased MHC-I expression and enhanced immunogenicity. In a syngeneic orthotopic model, PP2Ac loss prolongs survival in an immune- and CD8-dependent manner, indicating enhanced immune-mediated tumor clearance. Analysis of MB patient datasets links senescence signatures with improved survival, and integrative single-cell analysis reveals reduced PP2A activity in immunogenic senescent clusters. Although the PP2A inhibitor LB-100 is under clinical investigation, it fails to cross the blood-brain barrier. To overcome this, we developed a lipid nanoparticle (LNP) formulation delivering siRNA against PP2Ac. LNP-siPP2Ac efficiently silences PP2Ac in vitro and, when locally delivered in vivo, extends survival and increases tumor MHC-I expression. These findings establish PP2A as a central modulator of senescence and immunogenicity in MB and support a therapeutic strategy that induces tumor cell senescence and enhances anti-tumor immunity for treatment of MB.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design:
PP2Ac knockout D425 and SJ (#2416) cells were generated using CRISPR. For #2416, cells were harvested for bulk RNAseq. For D425 cells were also treated sham or radiation (10Gy) before being harvested for bulk RNAseq.
PP2Ac knockout in Group 3 medulloblastoma syngeneic CTD cells was generated using CRISPR, and total RNA was harvested for bulk RNA‑seq.

first: Winson

last: Ho

first: Isha

last: Mondal

first: Jingjing

last: Liu

first: Rayond

last: Sun

last: Yu

first: Rongze

last: Lu


title: C1q and immunoglobulins mediate activity-dependent synapse loss in the adult brain.

city: London

first: Emir

last: Turkes

address: Gower St

department: UK Dementia Research Institute

institute: University College London

summary: C1q, the initiator of the classical complement cascade, mediates synaptic elimination during development and disease, yet the triggers for C1q deposition on synapses in the adult brain remain unclear. Using in vivo chemogenetics, we demonstrate that neuronal hyperactivity acts as a trigger for region-specific C1q deposition and synapse loss in the adult hippocampus of wild-type mice; importantly, C1qa deficiency abolishes this activity-dependent synapse remodeling. Conversely, suppressing perforant pathway hyperactivity in a mouse model of Alzheimer’s disease lowers local Aβ levels, reduces C1q deposition, and partially rescues synapse loss. Further, using spatial transcriptomics, live cell tracking, super-resolution microscopy and other molecular and cellular tools, we report a surprising role for B lymphocyte lineage antibody-secreting cells in the activity-dependent C1q deposition and synapse loss in the non-diseased adult hippocampus. Overall, our work suggests a functional link between neuronal hyperactivity and C1q-mediated synapse loss in the adult brain and introduces immunoglobulins as players in this process.

overall_design: The Visium Gateway Package from 10x Genomics (PN-1000316, 10x Genomics) was used to generate spatial transcriptomic data from two coronal brain sections from two different hM3Dq-expressing CNO-treated mice. Experiments were performed in an RNase-free environment in line with the manufacturer’s recommendations and user guides. The brain was dissected immediately without PBS or PFA perfusion, and fresh frozen directly within an OCT mould in an isopentane bath submerged in liquid nitrogen. The lateral parts of the brain were trimmed during cryosectioning to allow 10 m-thick coronal sections including both dorsal hippocampi to be cryosectioned into the capture area (6.5 mm x 6.5 mm area) of the Visium Gateway Gene Expression Slide (10x Genomics). Cryosections were taken at 1.9 mm posterior to bregma, more than 2.5 mm anterior to the injection site at 4.6 mm posterior to bregma. Cryosections were also taken adjacent to the sections used for Visium and from MEC to confirm increased ipsilateral GFP and c-Fos immunostaining respectively.

first: Gerard

last: Crowley

first: Minjung

last: Kim

first: Nathanael

last: O’Neill

first: Fateme

last: Ghasemi

first: Luca

last: Giudice

first: Sebastiaan

last: De Schepper

first: Benjy J. Y.

last: Tan

first: Benito

last: Maffei

first: Laís S. S.

last: Ferreira

first: Julie

last: Rebejac

first: Javier

last: Rueda-Carrasco

first: Margarita

last: Toneva

first: John Christian

last: Fajardo

first: Judy Z.

last: Ge

first: Zhengyue Grace

last: Yang

first: Paula

last: Korhonen

first: Phillip

last: Muckett

first: Damaris

last: Bennett

first: Camille

last: Paoletti

first: Tammie T. M.

last: Sow

first: David A.

last: Posner

first: Annerieke

last: Sierksma

first: Dimitra

last: Sokolova

first: Viktoras

last: Konstantellos

first: Leen

last: Ali

first: Kiavash

last: Movahedi

first: Andrew

last: F. MacAskill

first: Victor L. J.

last: Tybulewicz

first: Tarja

last: Malm

first: Gabriele

last: Lignani

first: Menna

last: R. Clatworthy

first: Soyon

last: Hong


title: BATF3 regulates chromatin accessibility during CD8+ T lymphocyte differentiation

city: Nagoya

first: Seitaro

last: Terakura

state: Aichi

address: 65 Tsurumai-cho, Showa-ku

department: Department of Hematology and Oncology

institute: Nagoya University Graduate School of Medicine

summary: CD8+ T lymphocytes differentiate from effector to memory cells following antigen clearance, with prolonged IL-2 production characterizing functional cytotoxic T lymphocytes (CTLs). To identify transcription factors associated with sustained IL-2 production, we compared influenza virus-specific and cytomegalovirus-specific CTLs, identifying Basic Leucine Zipper ATF-Like Transcription Factor 3 (BATF3) as a key candidate gene. BATF3 overexpression significantly enhanced cell proliferation in both virus-specific CTLs and CD19 chimeric antigen receptor T (CAR-T) cells while reducing cytokine production. ATAC-seq analysis revealed that BATF3 overexpression dynamically regulates chromatin accessibility, affecting diverse cellular processes including cytoskeletal organization, metabolic pathways, and cellular survival signaling. BATF3 specifically facilitated the critical transition from effector to memory phase. These findings establish BATF3 as a master regulator of CD8+ T cell fate determination through dynamic chromatin remodeling mechanisms.

overall_design: ATAC-seq was performed on CD8+ T cells transduced with BATF, BATF3, or untransduced control across a 14-day differentiation time course. 12 donor samples (6 pairs of technical duplicates) were collected at Day 0, Day 7, and Day 14, for a total of 36 samples.

first: Koji

last: Umemura

first: Yasuhiro

last: Kojima

first: Jakrawadee

last: Julamanee

first: Yusuke

last: Okuno

first: Yuki

last: Takeuchi

first: Fumiya

last: Ohara

first: Shihomi

last: Kuwano

first: Yoshitaka

last: Adachi

first: Ryo

last: Hanajiri

first: Hitoshi

last: Kiyoi


title: NanoString nCounter study of ICCR-engineered human T cells compared to nontransduced T cells.

city: Houston

first: Irene

last: Min

state: TX

address: 6565 Fannin Street

department: Radiology

institute: Houston Methodist Research Institute

summary: This study aimed to investigate the targeting efficacy of ICAM1-specific chimeric costimulatory receptor (ICCR)-T cells on solid tumor and to study the molecular changes that underlie ICCR functional activity. This objective was addressed by demonstrating superior ICCR-T cell targeting efficacy using allogeneic and autologous ICCR-T cells on anaplastic thyroid cancer (ATC) cells in vitro. ICCR-T cell activity was also tested in vivo using ATC xenografts. We delineated the mechanism by which ICCR enhances T cell proliferation and selective activation by analyzing downstream signal pathway activation, gene expression, and TCR sequencing.

overall_design: Two donor T cells (healthy donor 5 and anaplastic thyroid cancer (ATC) patient RM) were manufactured to express ICCR (ICCR-T) or not (Nontransduced, NT). We had two conditions (unstimulated or target tumor-stimulated). Healthy donor 5 derived T cells (NT and ICCR-T) was stimulated with 8505C ATC cells and 8505C tumor. RM-ATC T cells (NT and ICCR-T) were stimulated with autologous RM-ATC cells.


title: Evaluation of epithelial growth from colon organoids in Transwell systems and the impact of growth factors

city: South San Francisco

first: Xinming

last: Tong

state: California

address: 1 DNA Way

institute: Genentech Inv.

summary: To investigate the epithelial development of colon organoids cultured on Transwell plates, gene expression analysis was conducted at various stages of differentiation. The effects of multiple growth factors, including epidermal growth factor (EGF), transforming growth factor-alpha (TGFα), keratinocyte growth factor (KGF, also known as FGF10), and trefoil factor 3 (TFF3), as well as cytokines such as interleukin-2 (IL-2) and interleukin-10 (IL-10), on epithelial development were also evaluated.

overall_design: Colon organoids were dissociated and plated onto Transwell inserts in growth medium for 2 days, followed by a switch to differentiation medium for 7 days. RNA expression was measured at day 1 and day 2 in the growth medium, as well as at days 1, 3, 5, and 7 in the differentiation medium. To examine the effects of growth factors, all factors were added to the differentiation medium at a consistent concentration of 2.5 nM, and RNA expression was analyzed on day 9.

first: Tong

last: Xinming

first: Li

last: Jing


title: Role of non-coding RNAs in classical hodgkin’s lymphoma treated within the EuroNet-PHL-C2 study

city: Giessen

first: Vijay

middle: Kumar

last: Singh

address: Feulgenstrasse 12

department: Department of Pediatric Oncology, Hematology, and Immunodeficiencies

summary: Pediatric Hodgkin lymphoma (HL) is a highly curable malignancy, yet a significant proportion of patients show inadequate early treatment responses despite intensive chemotherapy. The ability to identify these patients at diagnosis or early during therapy is critical for guiding treatment intensity and improving long‑term outcomes while minimizing unnecessary toxicity. MicroRNAs (miRNAs) have emerged as promising biomarkers in HL due to their stability in blood, ease of detection, and central role in regulating gene expression relevant to tumor biology. This study aims to determine whether specific microRNA (miRNA) expression patterns can serve as predictive and prognostic biomarkers in pediatric Hodgkin lymphoma. It will identify signatures—defined by upregulated oncogenic and/or downregulated tumor‑suppressive miRNAs—associated with inadequate early PET (ERAqPET) responses after two cycles of OEPA chemotherapy. miRNA profiles at diagnosis and during treatment will be compared between ERAqPET‑positive and ERAqPET‑negative patients, and correlated with treatment outcomes to establish a biomarker profile for early risk stratification. The goal is to develop a clinically applicable tool to identify high‑risk patients before or early in therapy, enabling tailored treatment that preserves high cure rates while minimizing long‑term adverse effects.

overall_design: Small RNA sequencing was performed on serum samples from 35 pediatric patients with classical Hodgkin lymphoma, treated under the EuroNet‑PHL‑C2 trial, collected both before the start of therapy and after induction therapy.

first: Marius

last: Rohde

first: Dieter

last: Körholz


title: isl1a Coordinates Onset and Termination of Regeneration of the Zebrafish Lateral Line

city: Kansas City

first: Shiyuan

middle: (Cynthia)

last: Chen

state: MO

department: Computational Biology

institute: Stowers Institute for Medical Research

summary: Regenerative capacity varies widely across tissues and species. Most regeneration studies have focused on identifying genes and pathways that promote regeneration, whereas mechanisms that inhibit regeneration to enforce organ size control and prevent excessive proliferation remain less well defined. Here, we identify isl1a as a dynamically expressed negative regulator of hair cell regeneration in the zebrafish lateral line. isl1a is highly expressed during homeostasis but becomes transiently downregulated following hair cell loss. Loss of isl1a leads to expansion of support cells and enhanced hair cell differentiation, producing enlarged sensory organs with increased hair cell numbers after injury. Mechanistically, isl1a downregulation increases chromatin accessibility at pro-proliferative loci, including AP-1 transcription factors, and sustains expression of injury- and regeneration-responsive genes. Together, these findings demonstrate that injury-induced downregulation of isl1a promotes the initiation of regeneration, while its subsequent re-expression restricts the duration of the response, thereby fine-tuning hair cell regeneration and maintaining organ size control.

overall_design: RNA-seq profiling of mcherry+ sorted cells from isl1apsi97/she:mcherry sibling and mutant samples at 5dpf in homeostasis and 3 hr post neomycin treatment, and ATAC-seq profiling of mcherry+ sorted cell from isl1apsi97/she:mcherry sibling and mutant samples at 5dpf in homeostasis, 1 hr and 3 hr post neomycin treatment. All conditions were collected in biological triplicates.

first: Paloma

last: Meneses-Giles

first: Tatjana

last: Piotrowski

first: Kaelan J

last: Brennan


title: Gene body methylation suppresses intragenic transcription and permits epigenetic inheritance in a cnidarian

first: Alex

last: de Mendoza

address: Mile End Road. Fogg Building 5.14

department: School of Biological and Behavioural Sciences

institute: Queen Mary University of London

summary: DNA methylation is traditionally associated with silencing, yet in invertebrates most methylation accumulates in actively transcribed gene bodies, posing a longstanding paradox. Gene body methylation (gbM) has been hypothesized to stabilize gene expression, suppress intragenic transcription, or mediate environmental responses, yet direct experimental evidence for its function remains limited. Here, we use the cnidarian Nematostella vectensis to demonstrate that loss of DNA methylation results in viable embryos with only mild effects on gene expression. Instead, methylation depletion leads to extensive aberrant accessibility and spurious transcriptional initiation, particularly associated to transposable elements within normally methylated gene bodies. This supports a model in which gbM suppresses cryptic regulatory activity in broadly transcribed regions. We further show that abnormal methylation patterns are partially restored in the germline, with recovery biased toward transcriptionally active regions and excluded from repressive chromatin. These epimutations are inherited into the next generation, revealing the absence of epigenetic reprogramming. Our findings uncover a conserved protective role for gbM, demonstrate its capacity for transgenerational inheritance, and highlight its potential as a regulatory substrate for natural selection.

overall_design: Nematostella embryos were treated with GSK-3484862 for 25 hours post fertilization, or DMSO as control. Those embryos were then collected for RNA-seq, ATAC-seq, and EM-seq, to determine the transcriptional and epigenomic responses to DNA methylation loss. Adults resulting from those same treated individuals were crossed in a F1 generation. Those were also grown to 25 hpf, where EM-seq, ATAC-seq and RNA-seq were collected, to compare with the transcriptome and epigenome of the previous generation. We also generated crosses between wild type and GSK-treated individuals that were sequenced with Oxford Nanopore, to assess methylation inheritance at the haplotype level.

first: Lan

last: Xu

first: Richard

last: Heery

first: Damir

last: Baranasic

first: Bojan

last: Žunar

first: Boris

last: Lenhard


title: Macropinocytosis inhibition attenuates pro-fibrotic responses in lung fibroblasts and pulmonary fibrosis

first: Maria

middle: Elisa

last: Ruiz Echartea

state: Texas

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: We conducted a single cell RNA sequencing experiment to determine the effect of a macropinocytosis inhibitor (5-(N-ethyl-N-isopropyl)-Amiloride, EIPA) in Precision Cut Lung Slices.

overall_design: Precision Cut Lung Slices were inciuhbated with or without EIPA (12.5uM) for 72 hours. Culture media was changed every 36 hours . After treatment, slices were subjected to single cell RNA sequencing trough the 10X Genomics 5' Version 3.1  and sequenced trough the Illumina platform.

first: Konstantin

last: Tsoyi

first: Ivan

middle: O

last: Rosas

first: Coarfa

last: Cristian

first: Ruiz

last: Maria Elisa

first: Waich

last: Alan


title: Gene-Gene Interactions Between A LMNA Variant and Common Polymorphisms Drive Early-Onset Atrial Fibrillation [ATAC-seq]

city: Chicago

first: Asia

last: Owais

address: 840 S Wood Street

department: Cardiology

institute: University of Illinois at Chicago

summary: Atrial fibrillation (AF) is a common arrhythmia with a complex genetic basis, yet the molecular mechanisms linking rare and common variants remain unclear. Using induced pluripotent stem cell-derived atrial cardiomyocytes, we uncover a novel mechanism by which a rare pathogenic LMNA variant encoding Lamin A/C disrupts chromatin accessibility and gene regulation at AF-associated loci. Specifically, reduced accessibility at an SCN5A enhancer harboring an AF-associated variant leads to reduced sodium current, conduction abnormalities, and re-entrant AF. These electrophysiological defects are rescued by CRISPR-mediated activation of the SCN5A promoter and enhancer providing the first molecular evidence of epistatic gene-gene interactions driving arrhythmia risk and mechanistically linking atrial myopathy and AF. At the population level, we demonstrate carriers of LMNA proteinaltering variants with a high polygenic risk score are at two-fold increased risk of earlyonset AF, highlighting the need to integrate rare and common variants for more accurate AF risk assessment.

overall_design: ATAC sequencing of LMNA-S143P and S143Pcorrected iPSC derived atrial cardiomyocytes

first: Hammad

last: Farooq

first: Hanna

first: Prisca

last: Thami

first: Jaime

last: Desantiago

first: Talla

last: Abbas

first: Arif

last: Pavel

first: Bradley

last: Merril

first: James

last: Ware

first: Dawood

last: Darbar


first: Scott

middle: Andrew

last: Ochsner

department: Molecular and Cellular Biology

summary: We conducted a bulk RNA sequencing experiment to determine the effect of macropinocytosis inhibitor (5-(N-ethyl-N-isopropyl)-Amiloride, EIPA) in lung fibroblasts

overall_design: MRC-5 cells were stimulated with TGF-beta1 (10 ng/ml) for 24 hours in the presence of absence of EIPA (12.5 𝛍M) or DMSO (vehicle).

first: Neil

middle: J

last: Mckenna


title: Effect of the poly-ICLC vaccine adjuvant on prostate cancer patients’ PBMC

city: Acton

first: Manuel

middle: Xavier

last: Duval

state: MA

address: 12 Abel Jones Pl

institute: double-strand

summary:
Identify PBMC RNA quantities whose level might predict response to prostate HIT-IT treatment
Phase I Peripheral Blood Mononuclear Cell from 12 high risk prostate cancer patients

overall_design:
Patients’ PBMC under HIT-IT treatment were collected at baseline and at five time points (week 3, week 6, week 9, week 6 post surgery and week 12 post surgery.
study protocol: Open-label Phase I clinical trial using a dose-escalation strategy of poly-ICLC in patients with clinically-localized prostate cancer.

first: Sujit

middle: S

last: Nair

first: Dimple

last: Chakravarty

first: Ashutosh

middle: K

last: Tewari


title: Gene-Gene Interactions Between A LMNA Variant and Common Polymorphisms Drive Early-Onset Atrial Fibrillation

overall_design: RNA sequencing of WT, LMNA-S143P and S143P corrected iPSC derived atrial cardiomyocytes

last: Chen


title: Hypoxia-responsive interaction between Cyclin T1, BHLHE40, and Tim8-Tim13 regulates RNA Polymerase II

first: Ali

last: Shilatifard

address: 320 E Superior St

department: Department of Biochemistry and Molecular Genetics

institute: Northwestern University Feinberg School of Medicine

summary: P-TEFb regulates the pause release checkpoint on transcription by RNA Polymerase II. We sought hypoxia-specific interactions that could direct PTEF-b activity to hypoxia-responsive genes. Using a biochemical purification approach, we discovered a hypoxia-specific, chromatin-associated interaction between the P-TEFb subunit Cyclin T1 (CCNT1), the mitochondrial chaperone Tim8-Tim13 complexes, and the hypoxia-inducible, DNA-binding transcription factor BHLHE40. This interaction is conserved across diverse cell line models. Tim8-Tim13 complex disruption and BHLHE40 silencing both impair the transcriptional response to acute hypoxia by RNAPII in DLD-1 cells. HIF is not involved in the CCNT1/BHLHE40/Tim8-Tim13 interaction, and BHLHE40 expression is not entirely HIF-dependent: neither genetic HIF-1β knockout nor pharmacological inhibition of HIF-2α using belzutifan eliminates BHLHE40. Finally, BHLHE40 depletion compromises the proliferation of 786-O clear cell renal carcinoma cells, which constitutively express HIF-2α and hypoxia-responsive genes. Together, these findings reveal a HIF-independent regulatory axis in which Tim8a-Tim13 complexes and BHLHE40 that modulate PTEF-b activity in the transcriptional response to hypoxia.

overall_design: ChIP-seq of RNAPII, BHLHE40, and HIF-1A in a colorectal cancer cell line (DLD-1) with sgRNA-induced KO and shRNA-KD modifications to analyze impact of genetic background on response to hypoxia.

first: Shimaa

middle: H

last: Soliman

first: Simone

last: De Fabritiis

first: Lawrence

middle: A

last: Lin

first: Marta

last: Iwanaszko

first: Navdeep

last: Chandel


title: Epigenetic analysis of murine normal mammary gland fibroblasts (mNFs) and MMTV-PyMT cancer-associated fibroblasts (mCAF1) (H3K27ac ChIP-seq)

status: Public on Apr 09 2026

city: Santander

first: Fernando

last: Calvo

state: Cantabria

address: C. Albert Einstein, 22

institute: IBBTEC

summary: In comparison with normal tissue fibroblast (normal fibroblasts, NFs), cancer-associated fibroblasts (CAFs) have pathologically activated phenotypes that impact in a wide variety of tumoral processes including cancer cell growth and invasion, extracellular matrix (ECM) remodelling, angiogenesis and immune suppression. These phenotypes result from the establishment of altered gene expression programs that may be further sustained through epigenetic alterations. However, how epigenetic rearrangements influence CAF behaviour is not well delineated. Here, we identify aspartoacylase (ASPA) as a metabolic enzyme consistently repressed in tumour stroma and CAFs. We report a reciprocal crosstalk between ASPA and Transforming Growth Factor Beta (TGFβ) signalling that influences fibroblast behaviour. TGFβ suppresses ASPA expression in fibroblasts, whereas ASPA restrains TGFβ-dependent myofibroblast conversion, ECM remodelling, angiogenesis and pro-tumoral macrophage phenotypes. TGFβ/SMAD3-dependent transcriptional repression may require the activity of histone deacetylases (HDACs), which participate in epigenetic rearrangements modulating gene expression. Epigenomic analysis of the 3’ regulatory regions at the Aspa locus in murine MMTV-PyMT-derived breast cancer CAFs (mCAF1) as compared to normal murine mammary gland fibroblasts (mNFs), revealed a selective loss of H3K27Ac, an epigenetic mark of active enhancers. As expected, bona fide CAF marker genes such as Acta2, Fap, Lrrc15 and others presented increased H3K27Ac signal at regulatory regions in mCAF1, whereas peaks at NF marker genes (Cxcl1 and Pi16) were decreased. Our findings unveil ASPA expression in fibroblasts as a previously unknown gatekeeper of TGFβ responses and activation in cancer progression.

overall_design: ChIP-Seq of the histone modification H3K27ac of murine normal mammary gland fibroblasts (mNFs) and MMTV-PyMT cancer-associated fibroblasts (mCAF1). Primary NFs/CAFs were isolated and immortalized, and processed for epigenetic analyses

first: Miguel

last: Juliá


title: Spatial transcriptomic atlas of aggressive osteosarcomas reveals shared gene surface expression and immune landscape.

city: Villejuif

first: Gaël

last: Moquin-Beaudry

address: 114, rue Édouard-Vaillant

institute: Gustave Roussy

summary: Osteosarcoma remains a highly aggressive malignancy with limited advancements in treatment efficacy and survival rates over the past four decades. Current therapeutic strategies fail in a significant proportion of patients, leading to metastatic relapse and poor prognosis. The substantial genomic instability and cellular plasticity of osteosarcoma contribute to its complex biology, necessitating innovative approaches for improved diagnosis and treatment. In this study, we applied spatial transcriptomics (ST) to 26 osteosarcoma samples, primary tumors and metastatic or local relapse samples. We described diverse differentiation phenotypes, ranging from mostly undifferentiated to metaphyseal-like organized highly differentiated phenotypes. Despite the phenotypic variability within and across samples, a comprehensive surfaceome analysis identified 306 cancer-specific membrane protein genes, among which nine formed a robust osteosarcoma-specific theranostic signature validated in multiple bulk RNAseq datasets. Additionally, spatial analysis of immune cell dynamics confirmed the systemic lymphoid cell exclusion and distinguished between cancer-excluded and -infiltrating myeloid populations. This identified three distinct populations along the osteoclastic lineage, with a systematic cancer-infiltration capacity. Cancer-infiltrating potential was also associated with type I interferon response and specific integrin-mediated adhesion mechanisms. This study provides a valuable resource to improve the understanding of osteosarcoma biology. We also suggest new clinically relevant targets in osteosarcoma, enabling the development of adapted and targeted treatment strategies for patients with the hope of improving clinical outcomes in the future.

overall_design: 26 FFPE samples of primary (n=9) and relapse (n=17) osteosarcoma tumors were analyzed by spatial transcriptomics using the Visium V1 FFPE protocol.

first: Maria Eugénia

last: Marques Da Costa

first: Pierre

last: Knheisser

first: Corentin

last: Thuilliez

first: Baptiste

last: Audinot

first: Hanane

last: Zair

first: Nicolas

last: Signolle

first: Michael

last: McDermott

first: Marie-Dominique

last: Tabone

first: Jean-Yves

last: Scoazec

first: Birgit

last: Geoerger

first: Damien

last: Drubay

first: Nathalie

last: Gaspar

first: Antonin

last: Marchais


title: Skin-resident Langerhans Cells Drive Neuropathic Pain via Chemokine-Dependent Neuron-Immune Communication

city: chicago

first: Daniela

middle: Maria

last: Menichella

state: illinois

address: 303 E Superior

department: Neurology

institute: Northwestern University

summary: Single-cell RNA sequencing of paw epidermis from male and female C57BL/6J mice fed regular diet (RD) or high-fat diet (HFD) for 10 weeks, to investigate the role of Langerhans cells in painful diabetic neuropathy.

overall_design: scRNAseq was performed on paw epidermis from RD and HFD male mice (n=3 per group) and RD and HFD female mice (n=3 per group). Cells were sequenced using the 10x Genomics Chromium Single Cell 3' v3 platform and aligned to the mouse transcriptome (mm10-2020-A) using Cell Ranger 7.2.0.

first: Pacifico

last: Paola

first: George

last: Dale S.

first: Jayaraj

last: Nirupa D.

first: Ren

last: Dongjun

first: Coy-Dibley

last: James S

first: Veronesi

last: Sofia

first: Baldamani

last: Abdelhak

first: Andelic

last: Mirna

first: Cartelli

last: Daniele

first: Devigili

last: Grazia

first: Lombardi

last: Raffaella

first: Lauria

last: Giuseppe P

first: Paller

last: Amy S

first: Miller

last: Richard J

first: Menichella

last: Daniela M