title: Effect of miR-15b and miR-16-2 overexpression on gene expression profiles in the human T-cell acute lymphoblastic leukemia (T-ALL) cell line CUTLL1.

city: Madrid

first: María

last: Toribio

state: Madrid

address: Calle Nicolás Cabrera, 1. Campus Cantoblanco

department: Interactions with the environment

institute: Centro de Biología Molecular Severo Ochoa (CSIC-UAM)

summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy arising from the neoplastic transformation of immature T cells during their development in the thymus. Deciphering the developmental programs whose dysregulation leads to T-ALL pathogenesis is critical for the development of novel targeted therapies, which remain an urgent unmet need for the treatment of this disease. MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of numerous physiological processes and cancer. However, the specific role of miRNAs in human T- cell development and T-ALL pathogenesis remains largely unexplored. In this study, we comprehensively evaluated miRNA expression profiles across human T-cell development by microarray analysis and identified a dynamic expression pattern of miR-16-2, which is upregulated across early pre-T cell proliferative stages up to the resting stage of immature thymocytes immediately preceding TCRab expression, and decreased thereafter. We confirmed the coordinated regulation of miR-15b expression, consistent with the reported clustered genomic location of both miRNAs. Notably, functional studies identified the miR-15b/16-2 cluster as a negative regulator of early thymocyte proliferation, and showed that overexpression of miR-15b/16-2 in T-ALL cells impaired leukemic growth in vitro and tumor progression in patient-derived xenotransplantation assays. Mechanistically, miR-15b/16-2 expression represses the genes encoding BCL-2 and CYCLIN D3, leading to T-ALL apoptosis and cell cycle dysregulation, with an accumulation of G0-phase cells and a defective transition to the G2/M phase. Moreover, RNA-seq analysis revealed that miR-15b/16-2 expression in the human T-ALL cell line CUTLL1 represses cell cycle-associated pathways (i.e. G1-to-S transition, G2-to-M transition), upregulates apoptotic and programmed cell death pathways, and modulates genes associated to DNA replication and DNA damage repair. Overall, these findings support a novel function for miR-15b/16-2 as tumor suppressors in T-ALL, highlighting their role as promising targets for T-ALL therapy.

overall_design: RNA-seq profiling of human T-ALL cell line CUTLL1 transduced with lentiviral vectors encoding either GFP alone (mock control vector, GFP) or the miR-15b/16-2 genomic cluster together with GFP (MIRS). GFP-positive transduced cells were enriched by flow cytometry sorting 4 days after transduction. The experiment was performed in triplicate.

first: S

last: González-García


title: scRNA-seq analysis of liver nonparenchymal cells from the mice after pIVCL and sham surgery

status: Public on Mar 01 2026

city: Suita

first: Seiya

last: Kato

state: Osaka

address: 2-2, Yamadaoka

department: Gastroenterology and Hepatology

country: Japan

institute: Osaka University

type: Expression profiling by high throughput sequencing

summary: We performed scRNA-seq analysis on murin livers after partial inferior vena cava ligation (pIVCL), a mouse model of congestive hepatopathy. We identified connective tissue growth factor (CTGF) as one of the most upregulated genes in pericentral (zones 2 and 3) LSECs. The scRNA-seq analysis also showed that the integrin signaling pathway was activated and the expression of YAP/TAZ target genes was upregulated in pericentral LSECs.

overall_design: After liver perfusion with pronase and collagenase, hepatocytes were removed via low-speed centrifugation, and dead cells and erythrocytes were removed via density gradient centrifugation.

first: Hayato

last: Hikita

first: Tetsuo

last: Takehara


title: RNA-seq analysis of liver sinusoidal endothelial cells exposed to hydrostatic pressure stimulation

summary: Primary murine LSECs (mLSECs) were exposed to hydrostatic pressure (HP) stimulation. The expression of YAP/TAZ target genes such as CTGF and basement membrane-related genes such as COL4A1was upregulated in mLSECs exposed to HP stimulation.

overall_design: After incubation on a Collagen I-coated plate overnight, the cells were serum-starved for 6 hours and then exposed to periodic HP stimulation for repeated cycles (0.01 Hz) between 101 and 135 kPa (absolute) for 8 hours using our original HPS system. The system was maintained at 37°C in a CO2 incubator (5% CO2).


title: Chronic inflammation promotes gastric cancer progression via ADAM10-mediated cleavage of CX3CL1

status: Public on Feb 28 2026

city: Hangzhou

first: Sicheng

last: Zhao

address: binwen road

country: China

institute: Zhejiang Chinese Medical University

summary: Purpose: This study aimed to investigate the impact of chronic inflammation (CI) on gastric cancer (GC) progression and the underlying molecular mechanisms. Methods: A subcutaneous xenograft model using 615-strain mice was established to evaluate the pro-tumorigenic effects of CI. Proteome Profiler Mouse XL Cytokine Array was used to screen for key pro-tumorigenic cytokines induced by CI, and ELISA was employed for validation. single-cell RNA sequencing(ScRNA-seq) was performed to identify the cellular source of CX3CL1 in GC tumor tissues. CCK-8 and colony formation assays were used to assess the effect of CX3CL1 on GC cell proliferation, while wound-healing and Transwell assays evaluated cell migration. ADAM10 expression was measured in gastric cancer cells and tissues via qRT-PCR, Western blot, and immunofluorescence staining. Results: CI significantly accelerated gastric cancer progression. CX3CL1 expression was markedly higher in GC tissues than in normal gastric tissues, and high CX3CL1 expression was associated with poor prognosis in GC patients. CX3CL1 recombinant protein significantly promoted the proliferation and migration of GC cells. Mechanistically, CI upregulated the expression of ADAM10, which plays a key role in converting membrane-bound CX3CL1 to its soluble form. Conclusion: This study provided evidence that chronic inflammation could promote tumor progression through the activation of ADAM10/CX3CL1 axis in gastric cancer.

overall_design: Male 615-strain mice23 (4 weeks old) were obtained from the Laboratory Animal Center of the Institute of Hematology, China Academy of Medical Sciences and housed under specific pathogen-free (SPF) conditions. Chronic inflammation was induced by intravenous injection of lipopolysaccharide (LPS, 100 μg/kg) and subcutaneous injection of carrageenan (CA, 20 mg/kg) on alternate days24. Control mice received equal volumes of sterile saline. The modeling period lasted for 49 days. On day 28, mice were subcutaneously inoculated with 3×10⁶ MFC gastric cancer cells into the right axilla. Tumor growth was monitored every three days using calipers, and tumor volume was calculated using the formula:Volume = 1/2×(larger diameter)×(smaller diameter)². On day 49, mice were euthanized by CO2 inhalation followed by cervical dislocation. Tumors were then carefully dissected from the mice and immediately weighed using an electronic balance for subsequent analysis.

first: Guangji

last: Zhang

first: Tao

last: Jiang

first: Zhiyuan

last: Song

first: Jingcheng

first: Yunhai

last: Wei


title: Gene regulatory co-option drives birdsong neural circuit specialization [snRNA-seq]

status: Public on Mar 02 2026

city: Santa Cruz

first: Bradley

last: Colquitt

state: CA

address: 1156 High St, Sinsheimer Labs 329

country: USA

institute: University of California, Santa Cruz

summary: A defining feature of our species is the ability to manipulate our environment through the fine control of our hands and to communicate with others through the rapid and complex motor orchestration of human speech. The courtship song of songbirds shares a number of neural and behavioral similarities with human speech and other learned motor skills, providing a powerful model for understanding how enhanced motor skills develop at molecular and cellular levels. Birdsong is controlled by a specialized neural circuit whose properties enable high precision and speed. In particular, glutamatergic neurons in the birdsong motor region RA (Glut-RA) have higher spike rates and narrower action potentials than projection neurons in an adjacent motor region that does not control song, the dorsal intermediate arcopallium (Glut-AId). To identify candidate gene regulatory networks that establish the specialized properties of Glut-RA neurons, we performed single-nucleus profiling of gene expression and chromatin accessibility across song and non-song motor regions. We found that Glut-RA projection neurons and fast spiking interneurons (FSIs), a GABAergic type also characterized by high spike rates and narrow action potentials, share several transcriptional similarities. In particular, the transcription factor MAFB, which is essential for the development and fast-spiking physiology of FSIs in mice, is expressed in Glut-RA but no other projection neuron type. We found that MAFB transcription factor binding sites have enhanced chromatin accessibility specifically in glutamatergic neurons in RA relative to AId. Furthermore, gene regulatory network inference and in silico knockdown of MAFB expression reveal common MAFB targets in Glut-RA neurons and FSIs, and suggest that the transcription factor is necessary to specialize song Glut-RA neurons from non-song Glut-AId neurons. These data support a model in which birdsong projection neurons co-opt an interneuron gene regulatory program to enable the rapid physiological properties required for fast and precise birdsong performance.

overall_design: Several regions of the song system and comparator non-song regions were dissected from the brains of adult Bengalese finch (Lonchura striata domestica) males. The regions include, RA, HVC, and LMAN, and paired non-song regions, arcopallium, caudal nidopallium, and rostral nidopallium. Single-nucleus 3' RNA-seq libraries (10X Genomics) were prepared from these samples.

middle: M

first: Michael

middle: S

last: Brainard


title: Nanopore Direct RNA sequencing of mice hippocampal brain tissues

city: Winnipeg

first: Athanasios

last: Zovoilis

state: MB

address: 745 Bannatyne Ave

department: Biochemistry and Medical Genetics

country: Canada

institute: University of Manitoba

type: Non-coding RNA profiling by high throughput sequencing

summary: Oxford Nanopore enables direct RNA sequencing allowing for base calling of RNA modifications. However, current direct RNA sequencing protocols may not be detecting some classes of non-coding RNAs such as SINE RNAs produced by Short Interspersed Nuclear Elements (SINEs). Using mouse hippocampi RNA samples, we have established a novel Nanopore direct RNA-seq protocol that in addition to long poly A selected RNAs allows sequencing also of non-poly A RNAs as well as short RNAs < 200nt (including SINE RNAs and other non poly A non coding RNAs). We provide here as a resource the first direct RNA-sequencing performed in mouse brain tissues that includes both mRNAs and non poly A or short non-coding RNAs such as SINEs.

overall_design: In this study, we employed a transgenic mouse model of amyloid pathology, APP NL−G−F (APP) (Saito et al., 2014) and the respective wild type control C57BL/6J (WT). We have tested mice at the stage of symptom manifestation (that coincides with the active neurodegeneration phase and appearance of amyloid plaques (6 months - 6m/ APP: 3x mice, WT:3x mice), The mice were then sequenced by Nanopore sequencing direct RNA SQK-RNA_002 protocol using the PromethION platform.

first: Luke

last: Saville

first: Yubo

last: Cheng

first: Liam

last: Mitchell

first: Travis

last: Haight


title: Quantifying the fidelity of in vitro human cell culture systems using a biomedical foundation model

city: Cleveland

first: Scott

middle: T

last: Espenschied

state: Ohio

address: 9500 Euclid Ave

department: Inflammation and Immunity

institute: Cleveland Clinic Research

summary: Primary cell culture is fast becoming a dominant method for discovery work regarding human disease. Currently there are no methods to quantitatively benchmark these systems. Here we apply a uniform in vitro culture system of human intestinal epithelial cells to achieve this goal. We previously established methods for long-term 2-dimensional (2D) cultivation of mouse intestinal epithelial cells using an air-liquid interface (ALI) technique. Here, we further refined these methods for long-term 2D cultivation of human IECs, with histological and molecular features of differentiated intestinal epithelia. Leveraging the power and scalability of a biomedical foundation model (BMFM) trained on single cell RNA sequencing data (BMFM-RNA), we performed classification tasks to identify cell types across sample sources and to quantitatively benchmark our in vitro differentiated cells against cells collected from patient biopsies. We observed a striking concordance between our in vitro differentiated cells and the corresponding cell types in vivo for multiple differentiated secretory cell types. This novel approach using BMFM-RNA holds promise to expand our understanding of the regulatory mechanisms, including gene-gene regulation underlying homeostasis and regeneration, as well as the functions of rare and poorly understood lineages within the human intestinal epithelia. Moreover, these methods may be applicable to other organs, model systems, and experimental modalities. We propose that the framework used here can be deployed as a standard benchmarking methodology, ultimately improving the fidelity of primary human culture systems.

overall_design: Human rectal intestinal epithelial stem cells were expanded in matrigel then seeded on transwell filters and allowed to differentiate for either 2 or 7 days, after which cells were collected for single cell RNA sequencing

first: Satoru

last: Fujii

first: Ryan

middle: J

last: Musich

first: Thaddeus

last: Stappenbeck


title: USP18 inhibits protective immune responses and the intracellular control of Mycobacterium tuberculosis in macrophages.

city: Stockholm

first: Martin

last: Rottenberg

address: Solna vägen 9

country: Sweden

institute: Karolinska Institutet

summary: We compared the transcriptome  profile of M. tuberculosis-infected murine bone marrow derived macrophages (BMM) treated with either the USP18 small molecule inhibitor BB7 or an inactive control (NC),   and uninfected controls as described below.   We identified 710 differentially expressed genes (DEGs) between uninfected and Mtb BMM and 243 DEGs comparing Mtb-BB7 vs Mtb BMM, 129 of these DEGs were upregulated. Gene ontology (GO) analysis showed enrichment of pathways related to antiviral responses, innate immune activation and inflammasome signalling when comparing Mtb-BB7 vs Mtb BMM. Conversely, genes associated with stress responses, hypoxia  and antioxidant activity were downregulated in Mtb-BB7.

overall_design: RNA seq was performed in triplicate independent cultures of BMM treated either with10 mM uM BB7 or NC , infected 4 h after treatment with M. tuberculosis  at a MOI of 5:1. RNA was extracted 8h after Mtb infection from uninfected BMM controls (Control), Mtb infected BMM treated with NC (Mtb), and MGO-treated, Mtb-infected BMM  (Mtb-BB7).

first: Zhen

last: Gong

first: Qiao


title: Spatial transcriptomics of human FALD and normal livers

first: Seiya

last: Kato

summary: Spatial transcriptomic analysis was performed on Fontan-associated liver disease (FALD) and normal livers using CosMx Spatial Molecular Imager.

overall_design: CosMx technology, a high-plex spatial molecular imager (SMI), was used to analyze 2 FALD liver samples that were histologically diagnosed with cirrhosis and 1 donor liver sample. FFPE samples were sectioned (5 μm), mounted on VWR Superfrost Plus microscope slides. Anti-B2M/CD298, anti-PanCK, anti-CD45, and anti-CK8/18 antibodies and DAPI were used as morphological markers. The CosMx Human Universal Cell Characterization RNA Panel (1000-plex) + 9 custom genes, including CCN2, was used for the CosMx assay. The samples were prepared according to the manufacturer’s instructions. Cell segmentation was performed by combining image preprocessing and CellPose neural network models. Serial thin sections prepared from FFPE samples were stained with H&E and Sirius red for field of view (FOV) determination. Each FOV was 0.5 × 0.5 mm in size. The data were analyzed by the CosMx SMI instrument, followed by quality control, normalization, principal component analysis and clustering using the count matrix and subpopulation assignments of the reference scRNA-seq dataset on the AtoMx platform.

first: Hayato

last: Hikita

first: Tetsuo

last: Takehara


title: scRNAseq analysis of hepatocytes from liver cirrhosis patient

city: Minato City, Tokyo

first: Teh-Wei

last: Wang

address: 4 Chome-6-1 Shirokanedai

institute: IMSUT

summary: We used the Flex single-cell RNA sequencing platform (10x Genomics) to investigate the transcriptomic differences of hepatocytes between healthy and liver cirrhosis liver samples obtained from resected tissues (non-tumorous regions) of patients with colorectal cancer liver metastases and patients with hepatocellular carcinoma accompanied by liver cirrhosis.

overall_design: In this experiment, we obtained liver surgical specimens from patients with colorectal cancer liver metastasis (representing healthy liver tissue) and from patients with hepatocellular carcinoma accompanied by cirrhosis (representing cirrhotic liver tissue). Following tissue fixation, samples were dissociated into single-cell suspensions using the gentleMACS Dissociator in combination with Liberase. Hepatocytes were then processed for cDNA library construction and subsequent transcriptomic analysis.

first: Koji

last: Nishikawa

first: Makoto

last: Nakanishi


title: A CRISPR screen in human iPSC-derived neurons reveals convergent transcriptomic effects of neurodevelopmental disorder genes [CRISPR Screen]

city: New Haven

first: Huanyao

last: Gao

state: Connecticut

address: 300 George St., Suite 901

department: Department of Psychiatry

institute: Yale University

summary: Diverse risk genes have been identified for neurodevelopmental disorders (NDDs), but how these genes converge on similar biological pathways in neurons, and thus give rise to similar phenotypes, is unclear. Here, we apply a pooled CRISPR approach to target 23 (out of 29) NDD loss-of-function genes and examine convergent effects on gene expression across human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells, glutamatergic neurons, and GABAergic neurons. Points of convergence vary between these cell-types and are greatest in mature glutamatergic neurons, where they broadly regulate synaptic, epigenetic, and, unexpectedly, mitochondrial pathways. The strongest convergent networks were observed between NDD genes with shared biological annotations, clinical associations, and co-expression patterns in human post-mortem brain.  Drugs that were predicted to reverse convergent transcriptomic signatures and/or arousal and sensory processing behaviors ameliorated behavioral phenotypes in NDD model zebrafish. These results suggest that convergent effects of NDD risk genes could provide clinically useful insights. Code and secondary analysis data can be found on Synapse ( ID=syn72039767, link=https://www.synapse.org/Synapse:syn72039767/wiki/636167)

overall_design: Transient transcription factor overexpression from stable clonal hiPSCs was used to induce control hiPSCs to iNPCs (here SNaPs), Lentiviral Cas9v2-HygroR and pooled LentiArray-gRNA-PuroR CRISPR-KO library including 29 genes (ARID1B, ASH1L, CHD2, MED13L, NRXN1, PHF21A, SETD5, SIN3A, SMARCC2, BCL11A, CHD8, KDM5B, KDM6B, KMT2C, MBD5, PHF12, SKI, WAC, CREBBP, ASXL3, ANK3, POGZ, SCN2A, SHANK3, SLC6A1, PPP2R5D, FOXP2, DPYSL2) as well as scrambled gRNA were packaged as high-titer lentiviruses were transduced via spinfection three days prior to harvest (e.g., d4 for D7 iGLUTs, d18 for D21 iGLUTs, d33 for d36 iGABA) (MOI 0.3-0.5). The entire cell were then submitted for single cell RNAseq (10X single cell 5' v2 HT with CRISPR barcode kit) in four lanes per cell type, targeting 20,000 cells per lane for a total of ~80,000 targeted cells per cell type, at Yale Genomics Core.

first: Meilin

middle: F

last: Garcia

first: Kayla

last: Retallick-Townsley

first: April

last: Pruitt

first: Elizabeth

last: Davidson

first: Novin

last: Balafkan

first: Jonathan

last: Warrell

first: Tzu-Chieh

last: Huang

first: Alfred

last: Kibowen

first: Zhiyuan

last: Chu

first: Yi

last: Dai

first: Sarah

middle: E

last: Fitzpatrick

first: Ran

last: Meng

first: Annabel

last: Sen

first: Sophie

last: Cohen

first: Olivia

last: Livoti

first: Suha

last: Khan

first: Charlotte

last: Becker

first: Andre

middle: L

last: Silva

first: Jenny

last: Liu

first: Grace

last: Dossou

first: Jen

last: Cheung

first: Susanna

first: Sadaf

last: Ghorbani

first: Peter

last: Deans

first: Marisa

last: DeCiucis

first: Prashant

last: Emani

first: Hongying

last: Shen

first: Mark

last: Gerstein

first: Zuoheng

first: Laura

last: Huckins

first: Ellen

last: Hoffman

first: Kristen

last: Brennand


title: scRNA-seq analysis of the livers from the endothelial cell-specific CTGF KO mice after pIVCL

first: Seiya

last: Kato

summary: We performed scRNA-seq analysis on the livers from the endothelial cell-specific CTGF knockout (KO) mouse or control wild-type (WT) littermate after partial inferior vena cava ligation (pIVCL), a mouse model of congestive hepatopathy. The scRNA-seq analysis showed that CTGF knockout in LSECs suppressed the expression of YAP/TAZ target genes and basement membrane-related genes in LSECs caused by hepatic congestion.

first: Hayato

last: Hikita

first: Tetsuo

last: Takehara


title: HFD-inducued metabolic syndrome is promoted by JNK7b isoform

status: Public on Feb 27 2026

city: Worcester

first: Sithara Raju

last: Ponny

state: MA

address: 55 N Lake Ave

department: Program in Molecular Medicine

institute: UMass Chan Medical School

summary: JNK7b isoform promotes metabolic syndrome in a mouse model of obesity

overall_design: mRNA expression analysis of livers from male control and Rxra S65A mutant mice under HFD condition

first: Alexandra

last: Lee

first: Autumn

last: Gentzler

first: Declan

last: Fitzpatrick

first: Sithara

last: RajuPonny

first: Myoung

last: SookHan

first: Roger

last: Davis


title: Cellular Survivorship Bias as  a Mechanistic Driver of  Muscle Stem Cell Aging

status: Public on Feb 26 2026

city: Los Angeles

first: Jengmin

last: Kang

address: 615 Charles E Young Dr S

institute: University of California, Los Angeles

summary: Aging is characterized by a significant impairment in the ability of muscle stem cells (MuSCs) to efficiently contribute to muscle regeneration. Here we uncover a novel cause of this aging-associated stem cell dysfunction - a cell-specific survivorship bias that prioritizes stem cell persistence at the expense of functionality. We show here that, with age, muscle stem cells upregulate a tumor suppressor, NDRG1, which, by blunting the mTOR pathway, increases their long-term survival potential but comes at the cost of their ability to promptly activate and contribute to muscle regeneration. These findings suggest that delayed muscle regeneration with age may be the result of a tradeoff that favors long term stem cell survival over immediate regenerative capacity.

overall_design: In order to determine the extent to which the elevation of NDRG1 might be a causal driver of the impaired activation rate observed in old MuSCs, we generated a MuSC-specific conditional NDRG1 KO mouse model (Pax7CreER/+; NDRG1fl/fl;ROSAeYFP/+ ) to ablate NDRG1 in MuSCs following tamoxifen injection. We next sought to determine the molecular mechanism by which NDRG1 was eliciting its effects in old MuSCs. To this end, we sequenced the transcriptomes of MuSCs from aged WT and NDRG1cKO mice

first: Daniel

middle: I

last: Benjamin


title: scRNA-seq analysis of liver constituent cells from human FALD and normal livers

summary: scRNA-seq was performed on Fontan-associated liver disease (FALD) and normal livers using 10x Genomics Fixed RNA Profiling. The expression of connective tissue growth factor (CTGF) was upregulated in the EC cluster in the FALD livers. The scRNA-seq analysis also showed that the integrin signaling pathway was activated and the expression of YAP/TAZ target genes was upregulated in the EC cluster in the FALD livers.

overall_design: Frozen surgical liver tissue was cut into pieces approximately 1 mm3, fixed with formalin using a Chromium Next GEM Single-Cell Fixed RNA Sample Preparation Kit (10x Genomics), and then dispersed into single cells using gentleMACS (Miltenyi Biotec) according to the manufacturer’s instructions.


title: Thiolutin Extends Replicative Lifespan by Rewiring Yeast Transcription and Metabolism

status: Public on Feb 25 2026

city: Rzeszów

first: Mateusz

last: Mołoń

state: Rzeszów

address: Aleksandra Zelwerowicza 4

country: Poland

institute: University of Rzeszów

summary: This study examines the global transcriptomic response of Saccharomyces cerevisiae strain BY4741 to short-term exposure to thiolutin, a transcriptional inhibitor. Exponentially growing cells were treated with 3 µg/mL thiolutin for 3 hours and compared with untreated controls. RNA sequencing was performed using paired-end libraries prepared with the MGIEasy RNA Library Prep Set and sequenced on the BGISEQ-500 platform. Three independent biological replicates were analyzed per condition. Differential expression analysis using DESeq2 (Benjamini–Hochberg false discovery rate < 0.05) revealed extensive transcriptional remodeling affecting pathways related to ribosome biogenesis, oxidative phosphorylation, proteostasis, stress response, and aging-associated processes.

overall_design: Wild-type Saccharomyces cerevisiae BY4741 cells were cultured in YPD medium at 28°C to exponential phase. Cultures were divided into untreated controls and cells treated with 3 µg/mL thiolutin for 3 hours. Total RNA was isolated from three independent biological replicates per condition. Poly(A)-selected RNA libraries were prepared and sequenced using paired-end DNBSeq technology on the BGISEQ-500 platform. Gene-level read counts were generated and analyzed using DESeq2 to identify differentially expressed genes.

first: Patrycja

last: Kielar

first: Zofia

last: Kobylińska

first: Agnieszka

first: Jarosław

last: Winiarski

first: Monika

last: Kula-Maximenko

first: Sabina

last: Galiniak


title: Combination of single-cell and bulk RNA-seq reveals changes in the immune landscape in osteomyelitis

city: Changchun

first: zhenhua

last: zhu

address: Xinmin  Street 71#

institute: The First Hospital of Jilin University

summary: Objective: This study profiled the osteomyelitis immune micro-environment in depth, pinpointed driver genes and cell populations that fuel disease progression, and mined the data for actionable drug targets. Methods: We analyzed time-series transcriptomic sequencing data from mouse tibial osteomyelitis samples in dataset GSE168896. Fuzzy c-means clustering was applied to reveal gene sets linked to disease progression. Immune cell infiltration analysis was conducted through online tool ImmuCellAI-mouse. Furthermore, by leveraging single-cell sequencing data, we characterized immune cell subpopulations and pinpointed the key cell subtypes that exhibited in osteomyelitis mouse. Results: We identified six gene clusters exhibiting distinct temporal expression patterns and functional roles in osteomyelitis processes, such as leukocyte and lymphocyte activation, ossification. Single-cell sequencing analysis further revealed 7 distinct cellular subpopulations. Among these, M2-like macrophages demonstrated a significant increase following osteomyelitis. Arg+Sdc4+ Mac and Cxcl1+Ccl4+ Mac were new subpopulations of macrophages that emerged after osteomyelitis, the infiltration of Mif+Cd63+ Mac significantly increased. Besides, Cxcl2-Cxcr2 ligand-receptors contributed mostly in immune cells.

overall_design: Single cell RNA-seq profilling of bone marrow flox mouse, osteomylities flox mouse and Trim59-cKO mouse (flox_ctrl,flox_om,cko_om) two weeks after modeling.

first: Zhenhua

last: Zhu

first: Xiaopeng

last: Jing

first: Jun

last: Chen

first: Jie

last: Tan

first: Ji

last: Zeng

first: Zheng

last: Jin


title: PRMT5 Inhibition Triggers Functional ATM Deficiency and Sensitizes Pancreatic Cancer to CHK1 Blockade

city: Milwaukee

first: Angela

last: Mathison

state: WI

address: 8701 Watertown Plank Rd, HM034, HRC5125

department: Department of Surgery

institute: Medical College of Wisconsin

summary: PRMT5 inhibitors are under clinical investigation for pancreatic ductal adenocarcinoma (PDAC), but strategies to maximize their therapeutic efficacy remain undefined. Here, we report that pharmacologic inhibition of PRMT5 markedly reduces levels of the DNA damage response kinase ATM across multiple PDAC cell lines and different PRMT5 inhibitors, leading to a state of functional ATM haploinsufficiency. We find that this functional deficiency rewires checkpoint signaling, rendering PDAC cells reliant on the ATR-CHK1 pathway for survival. Consequently, we tested combined PRMT5 and CHK1 inhibition and found synergistic suppression of PDAC growth, accompanied by enhanced Caspase 3/7 activation, Annexin V staining, and DNA damage accumulation. Congruent with these results, RNA-seq demonstrated downregulation of cell-cycle and DNA repair genes along with the upregulation of cell death pathways, providing mechanistic insight into the cooperative effect. Moreover, in subcutaneous xenografts, the combination substantially reduced tumor volume, prolonged median survival, and did not affect overall health or body weight. Treated tumors showed reduced ATM and Ki67 with elevated γH2A.X. Together, these findings identify PRMT5 inhibition as a trigger of functional ATM haploinsufficiency that exposes a therapeutically actionable vulnerability to CHK1 inhibition, offering a rational, mechanistically-based combination strategy for this dismal disease.

overall_design: Pancreatic mRNA profiles of L3.6pl cells that were treated with 200 nM EPZ015938 and 1.95-2.34 nM prexasertib, alone or in combination, for 5 days. Three biological replicates per condition.  DMSO controls after 5 and 7 days of treatment were treated as a single control.

first: Madeline

last: Dzikowski

first: Gareth

last: Pollin

first: Shawna

last: Butler

first: Byambasuren

last: Enkhtuul

first: Jennifer

last: Gavina Chavez

first: Michael

last: Zimmermann

first: Raul

last: Urrutia

first: Gwen

last: Lomberk


title: scRNAseq analysis of hepatocytes from p16-Tom mice following CCl4 treatment

first: Teh-Wei

last: Wang

summary: We used the Flex single-cell RNA sequencing platform (10x Genomics) to investigate the transcriptomic differences between p16high (Tom+) and p16low (Tom-) hepatocytes from p16-CreERT2/R26-LSL-tdTomato mice following 4 weeks of CCl4 treatment.

overall_design: In this experiment, we obtained liver from p16-Tom mice following 4 weeks of CCl4 treatment. After tissue fixation, samples were dissociated into single-cell suspensions using the gentleMACS Dissociator in combination with Liberase. Hepatocytes were FACSorted through MitoBrilliant 646 and Hoechst staining then processed for cDNA library construction and subsequent transcriptomic analysis.

first: Koji

last: Nishikawa

first: Satoshi

last: Kawakami

first: Makoto

last: Nakanishi


title: Metabolic Atlas of Early Human Cortex Identifies Regulators of Cell Fate Transitions

first: Aparna

last: Bhaduri

institute: University of California Los Angeles

summary: Cortical development involves rapid progenitor expansion and cell diversification that is likely supported by tightly regulated metabolic programs, yet these programs, particularly in human development remain largely uncharacterized. Here, we generated a metabolic atlas of the early human cortex using primary tissue and stem cell-derived cortical organoids. Across developmental stages, we observed dynamic changes in core metabolic functions, including an unexpected increase in glycolysis and pentose phosphate pathway (PPP) activity during late neurogenesis. Manipulation of glucose availability in cortical organoids altered progenitor and neuronal composition, increasing outer radial glia and inhibitory neurons populations. Pharmacological and genetic inhibition of PPP enzymes recapitulated these cell fate changes and promoted radial glial maturation. Ribose was sufficient to rescue the radial glia gene expression changes, revert organoid cell type composition, and restore the levels of ATP and hypotaurine. These data identify a critical role for the PPP in modulating radial glia cell fate specification and generate a resource for future exploration of additional metabolic pathways in human cortical development.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: 10X GEMX single-cell (sc) and single-nuclei (sn) RNA-sequencing, and 10X OCM of cortical organoids subjected to a metabolic perturbation. These perturbations were 1) glucose depletion followed by snRNA-seq 2) pharmacologic inhibition of the pentose phosphate pathway followed by snRNA-seq 3) knockdown of pentose phosphate pathway enzymes with and without metabolite rescue  4) sequencing of 2D differentiation protocol or 5) in vivo manipulation of PPP pathway at either E10 to E12 with harvest at E12 or E13 to E15 with harvest at E15.

first: Bhaduri

last: Aparna

first: Mil

last: Jessenya

first: Soto

last: Jose


title: Physical Crowding in 3D Niche Regulates NSCs of Cell Junction and Differentiation

city: Changsha

first: Chaoyong

last: He

address: Tianma road

institute: Hunan university

summary: Neural stem cells (NSCs) maintain central nervous system (CNS) homeostasis through self-renewal and differentiation into neurons and glia. While physical crowding dynamically regulates NSCs niches during CNS development, yet its role in regulating NSCs fate remains unclear. Herein, we systematically investigated how NSCs crowding influences intercellular junction formation and differentiation in 2D and 3D niches. Using RNA sequencing, RT-qPCR, Western blotting, and immunofluorescence, we found that cell crowding promotes neuron differentiation in both systems. Notably, in 3D cultures, crowding robustly upregulated cell-cell junction genes and enhanced junction-mediated communication. These findings reveal that the 3D environment provides essential biophysical contexts for NSCs, in which cell crowding synergistically enhances differentiation through coordinated cell-cell and cell-ECM signaling. This study offers new insights into the role of physical niche cues in NSCs biology and provides valuable guidance for the design of biomimetic 3D culture platforms and regenerative strategies for neural tissue engineering.

overall_design: NSCs were isolated from cerebral cortices of 1–day-old neonatal Sprague-Dawley rats. After tissue pieces of dissociation, the mixed cortical cells were first passed through a 100 μm mesh of nylon cell strainer, then plated into tissue culture flasks. RNA-seq library preparation. Total RNA was isolated from each sample using the RNAmini kit (Qiagen, Germany). RNA quality was examined by gel electrophoresis and with Qubit (Thermo, Waltham, MA, USA). Strand-specific libraries were constructed using the TruSeq RNA sample preparation kit (Illumina, San Diego, CA, USA), through reverse transcription using S1000TM Touch Thermal Cycler (Bio Rad) at 53°C (45 min) - 85°C (5 min) - 4°C cycle. The generated cDNA was amplified, and quality estimated using Agilent 4200 (performed by CapitalBio Technology, Beijing). The sequences of libraries were finally obtained using the Illumina Novaseq6000 sequencer with pair-end 150 bp (PE150).

first: Yuyun

last: Liang

first: Xiaonan

first: Zhiyan

last: Wu

first: Jing

last: Yang

first: Ziyan

last: Chen

first: Hexu

last: Zhang

first: Cheng

last: Zhao

first: Liyang

last: Shi


title: C-terminal Occludin Peptide Suppresses Airway Inflammation via Barrier Restoration

city: Busan

first: Kyoung Seob

last: Song

address: Gamcheon-ro, Seo-gu, Busan 49267

department: College of Medicine

country: South Korea

institute: Kosin University

summary: Background: Occludin is a key tight junction protein that contributes to epithelial barrier integrity and inflammatory regulation. Although its structural roles are well characterized, the physiological relevance of its C-terminal domain in airway inflammation remains poorly defined.  Methods: Occludin expression in human lung disease tissues was examined by immunohistochemistry. Functional relevance was assessed using BEAS-2B cells overexpressing full-length occludin or C-terminal deletion mutants. A synthetic peptide derived from the occludin C-terminal core sequence was designed and evaluated for its anti-inflammatory and barrier-protective effects. In vitro assays included IL-8 secretion, transepithelial electrical resistance, cytoskeletal remodeling, mitochondrial function, ROS production, and transcriptomic profiling. Therapeutic efficacy was validated in a murine model of Pseudomonas aeruginosa LPS–induced airway inflammation, followed by cytokine analysis, histopathology, and immune profiling.  Results: Occludin expression was markedly reduced in inflamed human lung tissues. In BEAS-2B cells, occludin overexpression suppressed LPS-induced IL-8 release, restored barrier integrity, and reduced F-actin remodeling, whereas C-terminal deletion abolished these effects. The C-terminal occludin peptide significantly decreased IL-8 production, improved barrier function, and suppressed cytoskeletal changes, while a mutant peptide was ineffective. Transcriptomic analyses identified occludin as a central suppressor of inflammatory signaling. Mechanistically, the peptide inhibited p38 activation, preserved mitochondrial structure, and reduced ROS production. In vivo, peptide pretreatment improved survival, lowered IL-6, IL-8, and TNF-α levels, and reduced goblet cell hyperplasia and inflammatory infiltration. Immune profiling further revealed restored T-cell populations, reduced myeloid expansion, and enhanced M2 macrophage polarization.  Conclusion: The occludin C-terminal–derived peptide exerts robust anti-inflammatory and barrier-protective effects, representing a promising therapeutic candidate for LPS-induced and potentially broader inflammatory lung diseases.

overall_design: BEAS-2B cells were transfected with wild-type occludin or siRNA-occludin for 24 h and then incubated with LPS for 2 h, after which RNA sequencing analysis was performed.

first: Hyun-Chae

last: Lee

first: Jeongtae

last: Kim

first: Jaewon

last: Shim

first: Tae-Jin


title: β-Nicotinamide mononucleotide restores mitochondrial function and muscle strength in septic male mice

city: Toon

first: Mari

last: Saida

state: Ehime

address: shitsukawa

department: Emergency and Clitical care medicine

institute: Ehime university

summary: Sepsis remains a leading cause of mortality and long-term disability, with survivors frequently developing intensive care unit–acquired weakness (ICU-AW) as part of post–intensive care syndrome. Here, to identify a nutritional therapy for ICU-AW, we investigated the mechanisms underlying sepsis-induced skeletal muscle dysfunction using a cecal slurry-induced sepsis mouse model. Although body weight and skeletal muscle mass recovered at 14 days after sepsis induction, muscle strength remained impaired, accompanied by persistent mitochondrial abnormalities. Transcriptomic analysis revealed that the pathways termed “Sirtuin signaling pathway” and “Mitochondrial dysfunction” significantly enriched with downregulation of Sirt3 which is a major mitochondrial NAD⁺-dependent deacetylase. Biochemical analyses confirmed increased acetylated lysine of mitochondrial proteins in septic muscle tissue. Among them, mass spectrometry identified complex I subunits as candidate substrates of Sirt3. Knockdown of Sirt3 in C2C12 myotubes impaired mitochondrial respiration, whereas treatment with β-nicotinamide mononucleotide (β-NMN) partially rescued energy production. In vivo, acute-phase administration of β-NMN preserved mitochondrial morphology and restored muscle strength without altering muscle mass. These findings demonstrate that sepsis induces mitochondrial dysfunction and persistent muscle weakness through Sirt3 downregulation, and highlight β-NMN supplementation as a promising NAD⁺-targeted therapeutic strategy for mitigating ICU-AW.

overall_design: To investigate the effects of sepsis on skeletal muscle, gastrocnemius muscles were isolated from control mice or from mice subjected to cecal slurry–induced sepsis for 4 days, and gene expression profiling analysis was performed using RNA-seq.

first: Yuuki

last: Imai


title: FOXO1 integrates endothelial hemodynamic, inflammatory and metabolic pathways in atherosclerosis [LSS]

status: Public on Feb 24 2026

first: Hanqiang

last: Deng

state: CT

address: 116 Court Street

department: Yale Cardiovascular Research Center

summary: Atherosclerosis occurs preferentially in regions of disturbed or low fluid shear stress (FSS), whereas physiological laminar FSS protects against disease by suppressing endothelial inflammation. Pro- vs anti-inflammatory programs are associated with glycolysis vs mitochondrial metabolism, respectively. Endothelial cells (ECs) sensing FSS from blood flow regulate these responses, but the underlying mechanisms are poorly understood. The transcription factor Forkhead box protein O1 (FOXO1) is known to regulate endothelial metabolism, yet its role in FSS-regulated endothelial inflammation remains largely unclear. We found that Oscillatory FSS and inflammatory cytokines induce, whereas physiological FSS inhibits FOXO1 nuclear translocation. RNA sequencing revealed that FOXO1 depletion in ECs upregulates the protective flow-responsive transcription factors KLF2/4 and reduces oscillatory FSS-induced inflammatory genes. Inhibition of FOXO1 nuclear translocation by physiological FSS is mediated via a KLF2-CDK2 pathway, with the latter phosphorylating FOXO1 at S249. Artery ECs-specific deletion of FOXO1 significantly reduces atherosclerotic plaque formation in hyperlipidemic mice. Inhibition of glycolysis attenuates OSS-induced FOXO1 nuclear translocation, suggesting a role for metabolic regulation. Notably, treatment with lactate promotes FOXO1 nuclear localization and lactylation, which is mediated by a lactyltransferase AARS1 (Alanyl-tRNA synthetase). These findings identify FOXO1 as a key mediator linking atheroprone flow and endothelial inflammation, suggesting potential new therapeutic targets for treating atherosclerotic cardiovascular disease.

overall_design: Human umbilical vein endothelial cells (HUVECs) were transfected with Ctrl (siCtrl) or FOXO1 (siFOXO1) siRNA for 3 days, then subjected to low shear stress (LSS; 3 dynes/cm2) for 24 hours. Total RNA was extracted and subjected to RNAseq, n=3 samples for each group.


title: DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis

city: Kanpur

first: Bushra

last: Ateeq

state: Uttar Pradesh

address: Lab-4, BSBE, Indian Institute of Technology Kanpur, Kalyanpur

department: Department of Biological Sciences and Bioengineering

country: India

institute: Indian Institute of Technology Kanpur

summary: Higher expression of Dyskerin Pseudouridine Synthase 1 (DKC1) associates with poor prognosis in colorectal cancer (CRC) patients. However, the mechanism associated with DKC1 upregulation, and its functional significance in disease pathogenesis and therapeutic resistance remains largely unexplored. Here, we performed global transcriptome sequencing outlining the molecular mechanism associated with DKC1 depletion in CRC. We show a positive feedback loop between canonical WNT signaling and DKC1, which orchestrates DKC1 expression.  Moreover, we show the role of altered sphingolipid metabolism upon DKC1 abrogation in imparting CRC oncogenicity and first-line chemotherapeutic resistance.

overall_design: RNA-seq was performed on scramble (shSCRM) control and DKC1 knockdown (shDKC1-2 and shDKC1-3) SW620 cells using two distinct lentiviral shRNAs stably silencing DKC1 gene.

first: Ateeq

last: Bushra

first: Khan

last: Umar

first: Goel

last: Ayush

first: Nigam

last: Shivansh


title: HFD-induced metabolic syndrome is promoted by JNK7b isoform

first: Sithara Raju

last: Ponny

overall_design: To elucidate liver cell heterogeneity and the changes in immune cell types by HFD, we perforemd ScRNA Seq on isolated liver leukocytes.

first: Alexandra

first: Autumn

last: Gentzler

first: Declan

last: Fitzpatrick

first: Sithara

last: RajuPonny

first: Myoung Sook

last: Han

first: Roger

last: Davis


title: Siglec-F Protects Against Elastase-induced Lung Inflammation and Emphysema in Mice

city: Aurora

first: Qihua

last: Ye

state: CO

address: Research Complex II  12700 East 19th Avenue

department: Pulmonary

institute: University of Colorado Anschutz Medical Campus

summary: Airspace macrophages (AMs) are essential for maintaining lung homeostasis. Their activity must be tightly controlled to prevent excessive immune responses and tissue damage, such as emphysematous alveolar destruction. Siglec-F is a canonical marker of AMs, but its functional role in lung disease remains unclear. Here, we investigated the role of Siglec-F in a murine model of elastase-induced emphysema. We found that Siglec-F-deficient mice exhibited worsened emphysematous phenotypes, along with accumulation and transcriptional reprogramming of resident AMs (RAMs). Transcriptomic profiling of Siglec-F-deficient RAMs revealed dysregulation of key pathways involved in tissue repair, including extracellular matrix degradation, TGF-β signaling, and phagocytosis. These findings demonstrate that Siglec-F is critical for restraining RAM activity and preserving alveolar integrity during injury. Our study provides new insight into the immunoregulatory function of Siglec-F in a tissue-destructive context and highlights the potential protective roles of Siglec signaling in chronic lung disease.

overall_design: Bulk RNA-seq of FACS-sorted CD11c+ resident airspace macrophages (RAMs) from the lung lavage of Siglecf+/+ (WT) and Siglecf-/- (KO) mice on days 0, 3, 7, 21 post porcine pancreatic elastase (PPE) administration.

first: Naoko

last: Hara

first: Yan

last: Hu

first: Sophie

last: Gibbings

first: Ting-Hui

last: Tu

first: Marika

last: Orlov

first: Ayako

last: Kato

first: Bradford

last: Smith

first: Tonya

last: Brunetti

first: Rachel

middle: Z

last: Blumhagen

first: Zhenghui

last: Liu

first: Bifeng

last: Gao

first: Patrick

last: Hume

first: Melanie

last: Königshoff

first: William

last: Janssen

first: Christopher

last: Evans


title: HFD-inducued metabolic syndrome is promoted by JNK7b isoform.

first: Sithara Raju

last: Ponny

overall_design: Livers were harvested from HFD-fed hepatocyte-specific JNK spliceoform mice over the course of a 24h period every 3 hours to analyze changes in circadian gene expression between groups:: LJ1J2control (GFP),  LJ1J27a (CRE) and LJ1J27b (FLPO). Liver mRNA was isolated and sequenced.

first: Alexandra

last: Lee

first: Autumn

last: Gentzler

first: Declan

last: Fitzpatrick

first: Sithara

last: RajuPonny

first: Myoung

last: SookHan

first: Roger

last: Davis


title: The emergence of multiple testicular cell lineages in human stem cell-derived testis-like organoids [RNA-Seq]

city: Parkville, Melbourne

first: Svenja

last: Pachernegg

state: VIC

address: 50 Flemington Road

department: Genomic Medicine

country: Australia

institute: Murdoch Children's Research Institute

summary: Reproductive development is a complex process orchestrated by precise gene expression and cellular interactions. Disruption to this process can result in Differences of Sex Development (DSDs) which occur in approximately 1-2% of live births. We have previously developed a protocol to differentiate human induced pluripotent stem cells (hiPSCs) into testis-like organoids as a model to study the molecular mechanisms underlying reproductive development and DSD. Here, we performed bulk and single-cell RNA sequencing on testis-like organoids to investigate their transcriptional landscape. Transcriptomic analysis revealed six cell clusters expressing markers associated with bipotential, early Sertoli, and testicular interstitial cells. To address the limited emergence of mature cell types, we generated a doxycycline-inducible NR5A1/SF1 hiPSC line, which successfully triggered the expression of Leydig cell markers upon overexpression. Our findings provide a comprehensive transcriptional profile of hiPSC-derived testis-like organoids, offering insights into human fetal gonadal development and a novel disease modelling system for DSDs.

overall_design: RNA seq profiling of hiPSCs (day -1 of differentiation) and hiPSC-derived testisl-like organoids at day 18 of differentiation

first: Gorjana

last: Robevska

first: Lucas

middle: G

last: Ferreira

first: Natalie

last: Charitakis

first: Jinchao

last: Gu

first: Eliza

last: Martin

first: Jan

last: Terhag

first: Denis

last: Bienroth

first: Jocelyn

last: van den Bergen

first: Sean

last: Wilson

first: Ben

last: Rollo

first: Melissa

middle: H

last: Little

first: Mirana

last: Ramialison

first: Andrew

last: Sinclair

first: Katie

last: Ayers


title: The emergence of multiple testicular cell lineages in human stem cell-derived testis-like organoids [scRNA-Seq]

overall_design: single cell RNA-seq of hiPSC-derived testis-like organoids at day 21 of differentiation


title: A Functional Cell Model using Basophil Activation Test to Study Molecular Mechanisms and Biomarkers of Response to Omalizumab Treatment in Patients with Asthma

city: Maribor

first: Mario

middle: Smode

last: Gorenjak

address: Taborska ulica 8

country: Slovenia

institute: Faculty of Medicine, University of Maribor

summary: Patients with severe asthma may benefit from targeted biological therapies. However, personalized therapy in children and adolescents with asthma, based on individual susceptibility to molecular mechanisms addressed by different biologicals is underdeveloped. Here we established a functional in vitro model to study the differential responses of asthma patients to omalizumab (an IgE targeting biological) therapy. White blood cells isolated from asthmatic children and adolescents were pre-treated with omalizumab. Next, basophil activation and degradation were used to assess the in vitro patient’s response to omalizumab after exposure to patient-specific allergens. In parallel, basophils-specific whole RNA sequencing was used to screen for differentially expressed genes associated with in vitro response to omalizumab. The results of the screen were first confirmed in an independent cohort of patients and finally compared to the clinically relevant data. The in vitro basophil activation + degradation test may be used to study the differential response to omalizumab in patients. The differentially expressed genes in the basophils of the better vs. the poor / non-responders are predominantly associated with defense against viruses and apoptosis. The low RSAD2 expression correlates with poor response to omalizumab in vitro and with high FeNO levels (an indicator of lung inflammation) in the omalizumab-treated juvenile asthmatics. We describe an in vitro test to study the differential response to omalizumab in patients. RSAD2 may be a biomarker for response to omalizumab in asthma.

first: Boris

last: Gole

first: Larisa

last: Goričan

first: Gregor

last: Jezernik

first: Uroš

last: Potočnik

first: Anja

last: Bizjak

first: Vojko

last: Berce


title: Questiomycin A demonstrates antibacterial activity against Mycobacterium tuberculosis by directly targeting FabD

city: Beijing

first: ling

middle: ling

last: xu

address: Beimachang No 97

department: Department of Pharmacology

institute: Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute

summary: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat, particularly due to the rise of multidrug-resistant TB (MDR-TB). Current treatment limitations highlight the urgent need for new therapeutics to improve efficacy and shorten therapy duration. Through high-throughput screening, we identified Questiomycin A (QM), a phenoxazinone compound with promising anti-tuberculosis activity against drug-sensitive and drug-resistant Mtb strains. Transcriptomic profiling indicated disruption of cell wall-associated pathways, while thermal proteome profiling (TPP) identified fabD (malonyl CoA-acyl carrier protein transacylase, MCAT), a key enzyme in mycolic acid biosynthesis, as a potential target. Surface plasmon resonance (SPR), enzymatic assays, and genetic manipulation confirmed QM directly binds to and inhibits fabD. QM disrupts cell wall integrity, increases permeability, and causes pH imbalance, proton motive force collapse, ultimately resulting in bactericidal effects. These findings reveal that QM targets fabD to compromise cell wall homeostasis in Mtb, providing a foundation for developing novel anti-tubercular agents targeting fabD.

overall_design: Mtb H37Rv treated with DMSO or QM (4 × MIC) for 6 h. Cells were harvested after treatment with RNA protect bacterial reagent (Qiagen, Germany), lysed in RLT buffer + β-mercaptoethanol, and disrupted with zirconia beads. Total RNA was extracted using RNeasy Mini Kit (Qiagen, Germany) and eluted with DEPC water.

first: Lingling

last: Xu

first: Manyi

first: Bin

last: Wang

first: Xinda

last: Li

first: Qiyue

last: Jia

first: Chennan

last: Liu

first: Yangxue

last: Ye

first: Zimo

first: Lu

first: Weiyan

last: Zhang

first: Yu

last: Lu


title: Genomic characterization of mouse hindlimb skeletal muscles with divergent slow myofiber content at an embryonic and adult time point [ATAC-Seq]

city: Cambridge

first: Terence

last: Capellini

address: 11 Divinity Avenue

department: Human Evolutionary Biology

institute: Harvard University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Here, we characterize the genomic landscape of four mouse hindlimb muscles that differ in slow myofiber content at two time points (E18.5 and adult) to identify novel enhancers that may underlie the expression of genes involved in myofiber development and physiology. RNA-seq analysis revealed that fast- and slow-biased muscles show divergent patterns of gene regulation beginning at a late embryonic time point and persisting through adulthood. Genes differentially expressed between adult fast- and slow-biased muscles were enriched with biological pathways unique to each myofiber type, with glycolytic pathways characterizing adult fast-biased muscles and mitochondrial biogenesis and lipid metabolism characterizing adult slow-biased muscles. By integrating differential expression analysis (RNA-seq) with differential accessibility analysis (ATAC-seq) we identified twelve conserved, muscle-specific candidate enhancers nearby differentially expressed genes that regulate cell metabolism and the genetic markers of myofiber type. Nine candidate enhancers significantly increased and three significantly decreased luciferase reporter activities in C2C12 cells, highlighting the dynamic role of tissue-specific enhancers and repressors on development and differentiation. However, further validation is needed to see if these enhancers regulate the expression of target genes and the effect on muscle myofiber content. Collectively, these results highlight the importance of conserved, skeletal muscle-specific enhancers on skeletal muscle development and adult myofiber phenotypes and provide additional genomic targets for further validation.

overall_design: Examination of open chromatin regions (ATAC-seq) and differentially expressed genes (RNA-seq) in mouse hindlimb muscles with divergent slow myofiber content at an embryonic (E18.5) and adult (P56) time point.

first: Samantha

middle: R

last: Queeno

first: Alexander

last: Okamoto

middle: D

first: Kirstin

middle: N

last: Sterner


title: HFD-inducued metabolic syndrome is promoted by JNK7b isoform

first: Alexandra

last: Lee

summary: The JUN NH2-terminal kinase (JNK) signal transduction pathway is activated during the hepatic metabolic stress response. The pre-mRNAs expressed by the Mapk8 and Mapk9 genes (encode JNK1 and JNK2) in hepatocytes exhibit mutually exclusive inclusion exons 7a or 7b that encode a segment of the substrate binding site that is required for selective protein phosphorylation. We established mice with conditional inclusion of exons 7a / 7b to test the function of JNK spliceoforms. We report that the JNK27b spliceoform plays a key role in the hepatic metabolic stress response by suppressing signaling by the nuclear hormone receptor PPARa. This function of JNK27b is mediated by an integrated mechanism involving circadian dysfunction and the phosphorylation of the PPARa partner protein RXRa on Ser265. Our analysis identifies a key role for a specific JNK spliceoform in the hepatic adaptive response to metabolic stress.

overall_design: mRNA expression of brains from control and single isoform KO mice under normal diet condition was analyzed to evaluate exon usage and characterize our novel mouse model

first: Autumn

last: Gentzler

first: Declan

last: Fitzpatrick

first: Sithara Raju

last: Ponny

first: Myoung Sook

last: Han

first: Roger

last: Davis


title: HFD-inducued metabolic syndrome is promoted by JNK7b isoform [Liver_RNAseq]

overall_design: livers were harvested from HFD-fed hepatocyte-specific JNK spliceoform mice: LJ1J2control (GFP),  LJ1J27a (CRE) and LJ1J27b (FLPO) and liver mRNA was sequenced.

first: Myoung

last: Sook Han


title: CRISPR-based genetic screens to interrogate therapeutic targets on tumor maintenance and heterogeneity in AML patient cells

city: Philadelphia

first: Jacqueline

last: Peng

state: PA

address: 421 Curie Blvd

institute: University of Pennsylvania

summary: Functional genomics directly in primary tumor cells is warranted to better understand the complexity of the diseases in a context of high clinical relevance. We optimized ex vivo and in vivo CRISPR-based genome/epigenome editing approaches in patient-derived xenograft (PDX) and primary acute myeloid leukemia (AML) cells, including those harboring DNMT3A/FIT3-ITD/NPM1c that predicts a poor clinical outcome and has no model to fully represent. We deployed CRISPR and CRISPRi “drop-out” screenings on patient cells in vivo and prioritized AML-biased gene and cis-element dependencies, including an uncharacterized MYB regulatory element. We further developed a Perturb-seq pipeline for patient cells, where we perturbed known AML therapeutic targets and delineated complex regulatory networks and changes of cell cycle stages and cellular hierarchy in response to perturbations by scRNA-seq. We uncovered an unanticipated role for SETDB1, a suppressor of interferon response, whose depletion caused the emergence of Hematopoietic stem cell (HSC) and progenitor-like population marked with high HOXA expression in a PDX model, and myeloid differentiation were re-induced by DOT1L inhibition, preceding a combinatorial therapy to co-suppress SETDB1 and the HOXA cluster. Our study proposed a strategy to annotate personalized vulnerabilities to predict therapeutic response in AML.

overall_design: mRNA profiles of Cas9 sgRNA-expressing human primary samples and PDX samples

first: Zhendong

last: Cao

first: Jonathan

last: Sussman

first: Jason

last: Xu

first: Changya

last: Chen

first: Kai

last: Tan

first: Junwei

last: Shi


title: Chronic PFOA and PFOS Exposure Triggers Cellular Oxidative Stress and Alters Lipid Levels as Revealed through Multi-omics Analysis

city: Buffalo

first: Omer

last: Gokcumen

state: NY

address: 135 Founders Promenade

department: Biological Sciences

institute: University at Buffalo

summary: Per- and polyfluoroalkyl substances (PFAS), or "forever chemicals," are linked to metabolic, immune, and neurotoxic disorders, yet their long-term cellular effects remain unclear. Using a 24-week chronic exposure model with non-transformed human epithelial cells, we examined responses to low, environmentally relevant concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). Integrated transcriptomic and lipidomic analyses revealed that despite minimal cellular accumulation, molecular changes emerged around week 17, marked by transcriptional signatures indicative of oxidative stress responses, cell survival pathways, and lipid metabolism. Our data suggests a multi-faceted model in which long-term PFOA and PFOS exposure induces oxidative stress mediated by SESN2 and SOD3 , increases lipid biosynthesis via SREBP pathway, and causes compound-specific disruptions of membrane lipids. These findings highlight the importance of multi-omic, time-resolved approaches in uncovering the mechanisms of chronic low-dose chemical exposure and provide a foundation for future in vivo studies.

overall_design: hTERT RPE-1 cells were exposed to MeOH (vehicle control), perfluorooctanoic acid (PFOA), or perfluorooctane sulfonic acid (PFOS) for 24 hours or 7, 17, and 24 weeks . Each condition includes three independent biological replicates (n = 3). Total RNA was extracted from each sample and subjected to paired-end RNA sequencing. Gene-level expression counts were generated and differential expression analysis was performed using DESeq2 to compare treatment conditions across time points.

first: Paddayuman

last: Jenise

first: Cristobal

last: Judith

first: Landau

middle: B

last: Luane J.

first: Ashleigh

last: Gagnon

first: Gokcumen

last: Omer

first: Aga

last: Diana S.

first: Atilla-Gokcumen

last: G. Ekin


title: Splicing fidelity infuences the fate of mRNA molecules

first: Athma

middle: A

last: pai

address: 55 Lake Avenue North

department: RNA Therapeutics Institute

institute: UMass Chan Medical School

summary: RNA splicing has historically been thought to be highly efficient and accurate, with little opportunity for deviation from regulated alternative splicing decisions. This dogma has been challenged by recent observations that suggest that biological noise may contribute substantially to transcriptome diversity. However, quantitative understanding of stochastic variations in splicing is challenging because these transcripts are likely subject to rapid degradation. Here, we use ultra-deep sequencing across RNA compartments to track splicing intermediates in human cells and see abundant cryptic splicing associated with genomic features that promote splicing noise. We observe pervasive usage of low-fidelity splice sites, likely due to stochasticity in recruitment or binding of the spliceosome. These sites are most likely degraded in the nucleus rather than targeted by translation-dependent degradation processes, suggesting widespread surveillance and quality control of non-productive RNA transcripts. Our findings provide unprecedented insights into the propensity for error in RNA processing mechanisms to buffer mechanistic noise.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design:
RNAseq from nascent, nuclear and polyA enriched fractions from K562, KNS60, AM38, SY5Y and HepG2 cell lines.
K562 cells were treated with cycloheximide, NMDi14, uridine, 4SU and DMSO, followed by polyA enriched RNAseq.
K562 cells were treated with cycloheximide and NMDi14 followed by polyA enriched RNAseq.
K562 cells were treated with IdU, with or without 4sU labelling, followed by nuclear isolation, without or without 4sU pulldown and RNAseq
Amplicon sequencing: PCR amplification was done using primer pairs flanking cryptic splice junctions  using cDNA generated from total RNA from nuclear fraction, and whole cell extracts isolated from K562 cells. (See Methods)

first: Eraj

last: Khokhar

first: Kaitlyn

last: Brokaw

first: Zachary

last: Kartje

first: Ye

last: Liu

first: Valeria

last: Sanabria

first: Nida

last: Javeed

first: Ayush

last: Kumar

first: Ezequiel

last: Calvo-Roitberg

middle: K

last: Watts

last: Pai


title: Effete and Cullin 4 affect nuclear organization of the gypsy chromatin insulator [RNA-Seq]

city: Bethesda

first: Elissa

middle: P

last: Lei

state: MD

address: 50 south drive, blg50

department: NIDDK

institute: NIH

summary: Chromatin insulators demarcate the genome into distinct transcriptional domains and contribute to higher-order genome organization. InDrosophila, Su(Hw), CP190, and Mod(mdg4)67.2 are core components ofgypsyinsulator complex. Insulator bodies are polymerization of insulator proteins in cell nuclei, and their proper localization is correlated with insulator function. Post-modification of insulator proteins is required to fulfill insulator function, but few proteins in this process have been revealed. Here, we identify Effete(Eff), a ubiquitin-conjugating enzyme, and its interactor Cul4 as novel regulators of insulator bodies localization through a high-content RNAi screen. Effete and Cul4 physically associate with gypsy insulator proteins and promote gypsy-dependent insulator barrier activity. Moreover, Effete enriches in Satellite DNA and gypsy sites shared by Su(Hw). Cul4 overlaps with CP190 and localizes to gene promoters. Effete and Cul4 have little overlap, but they mutually impact the chromatin binding of one another. Effete and Cul4 are required for the binding of Su(Hw) in repetitive sequences and regulate the transcription of genes near TAD borders. Depletion of Effete alters the chromatin organization and position of gypsy insulator in nuclei. Overall, our findings reveal novel regulation roles of ubiquitin enzymes in chromatin insulator activity, 3D genome organization, and gene expression

overall_design: To investigate whether Effete and Cul4 directly affect transcription genome-wide, we performed neuRNA-seq to examine newly synthesized transcripts in control cells versus Effete or Cul4 deficient cells.

first: Shue

last: Chen

first: Dagyeong

last: Yang


title: Immunotolerant Oligomer Scaffolds Promote Regenerative Remodeling and Improved Muscle Structure and Function After Volumetric Muscle Loss

city: West Lafayette

first: Rachel

last: Morrison

state: IN

address: 206 S Martin Jischke Dr

department: Weldon School of Biomedical Engineering

institute: Purdue University

summary: Volumetric muscle loss (VML) overwhelms endogenous repair mechanisms, leading to defect contraction, fibrosis, and persistent aesthetic and functional deficits. Restorative biomaterials capable of re-establishing muscle structure and function represent promising strategies for treating severe injuries where conventional surgical repair is inadequate. Using a rat full-thickness VML model, we evaluated Oligomer, an engineered collagen polymeric biomaterial through spatial transcriptomic profiling. Spatial transcriptomic analyses defined a regenerative remodeling mechanism distinct from reparative or constructive remodeling, characterized by an immunotolerant environment that enabled infiltration of diverse progenitor populations, including pro-regenerative mesenchymal cells, pericytes, satellite cells, and endothelial and neural stem cells. This cellular niche supported coordinated activation of myogenic, vascular, and neural pathways, recapitulating key aspects of developmental myogenesis.

overall_design: Spatial transcriptomcs was performed on tibialis anterior (TA) muscles treated with Oligomer Scaffolds. Samples were harvested at 2 and 8 weeks post-treatment (n=2-4 per time point), bisected at the defect midline, and embedded in OCT for cryosectioning.  Samples were flash frozen in liquid nitrogen and stored at -80°C.

first: Joshua

last: Sexton

first: Lujuan

last: Zhang

first: Eric

last: Dong

first: Hongyu

last: Gao

first: Yunlong

first: Stacey

last: Halum

first: Sherry

last: Voytik-Harbin


title: Loss of Histone Methyltransferase Ezh2 Exacerbates Polarization of Macrophages toward M2-Like Phenotypes by Hepatocellular Carcinoma [RNA-Seq]

status: Public on Feb 22 2026

city: Bangkok

first: Tanapat

last: Palaga

address: Payathai Road, Pathumwan

department: Microbiology

country: Thailand

institute: Chulalongkorn University

summary: The roles of histone methytransferase Ezh2 in TAMs of liver cancer still unclear. In this study, an RNA sequencing was performed for samples from bone marrow-derived macrophages (BMDMs) of WT and Ezh2 KO mice upon exposure to conditioned media (CM) from hepatocellular carcinoma (HCC) cell line Hepa1-6. The results demonstrated that the absence of Ezh2 in BMDMs exacerbated M2-like phenotypic changes upon incubation with CM from hepatocellular carcinoma (HCC) cell line. The RNA-sequencing revealed that the M2 gene set was further upregulated in treated BMDMs Ezh2 KO compared to treated BMDMs WT WT and the hallmark of Glycolysis as enriched pathway was identified in BMDMs Ezh2 KO. Additionally, the hallmark of IL-6/JAK/STAT pathway was enriched in CM-treated BMDMs. Collectively, these findings provide evidence that JAK/STAT3 axis is critical for M2-like phenotypic changes and Ezh2 suppresses the shifts of macrophage metabolism toward glycolysis that promotes M2 polarization.

overall_design: RNA-seq profiling of bone marrow-derived macrophages WT and Ezh2 KO that treated with conditioned media of mouse liver cancer cell line Hepa1-6 for 24 hours.

first: Kittin

last: Weerasopon

first: Atsadang

last: Boonmee

first: Patipark

last: Kueanjinda

first: Benjawan

last: Wongprom

first: Thitiporn

last: Pattarakankul


title: Loss of Histone Methyltransferase Ezh2 Exacerbates Polarization of Macrophages toward M2-Like Phenotypes by Hepatocellular Carcinoma [ATAC-seq]

summary: The roles of epigenetic regulator Ezh2 in TAMs of liver cancer still unclear. In this study, our results demonstrated that the absence of Ezh2 in bone marrow-derived macrophages (BMDMs) exacerbated M2-like phenotypic changes upon incubation with conditioned media (CM) from hepatocellular carcinoma (HCC) cell line Hepa1-6. The ATAC-seq revealed that the promoter regions of pyruvate metabolic process-related genes were more accessible in treated BMDMs Ezh2 KO.

overall_design: ATAC-seq profiling of bone marrow-derived macrophages WT and Ezh2 KO that treated with conditioned media of mouse liver cancer cell line Hepa1-6 for 24 hours.


title: Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice

city: Dallas

first: Samuel

middle: Kent

last: McBrayer

state: Texas

address: 6000 Harry Hines Boulevard, NL11.110K

department: Children's Research Institute

institute: UT Southwestern Medical Center

summary: Stable isotope tracing assays track few metabolites, yet cells use many nutrients to sustain nitrogen metabolism. Here, we create a platform for tracing 30 nitrogen isotope-labeled metabolites in parallel to enable a system-level understanding of cellular nitrogen metabolism. This platform reveals that while primitive cells engage both de novo and salvage pyrimidine synthesis pathways, differentiated cells nearly exclusively salvage uridine. This link between cell state and pyrimidine synthesis pathway preference persists in murine and human tissues. Mechanistically, we find that S1900 phosphorylation of CAD, the first enzyme of the de novo pathway, is induced by uridine deprivation in differentiated cells and constitutively enriched in primitive cells. Mimicking CAD S1900 phosphorylation in differentiated cells constitutively activates de novo pyrimidine synthesis, while blocking this modification impairs the cellular response to uridine starvation. Collectively, we establish a method for nitrogen metabolism profiling and define a mechanism of cell state-specific pyrimidine synthesis pathway choice.

overall_design: We performed RNA sequencing on HNF, NPC, neurons, and differentiating neurons under varying uridine concentrations.

first: Milan

last: Savani

first: Bingbing

last: Li

first: Tracey

last: Shipman


title: A single cell transcriptional profile of benign prostatic hyperplasia

city: San Francisco

first: Jon

last: Akutagawa

address: 513 Parnassus Ave

institute: UCSF

summary: Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single cell RNA-seq data was performed to annotate all cell types. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation. A rare luminal subgroup was identified and pseudotime analysis indicated this luminal subgroup might give rise to other luminal cells. Using a gene set derived from epithelial stem cells, we found that this luminal subgroup had a significantly higher stem cell signature score than all other epithelial subgroups, suggesting this subgroup is a luminal precursor state. Ligand-receptor interactions between stromal, epithelial, and immune cells were explored with CellPhoneDB. Significant interactions involving MIF, a pro-inflammatory cytokine that promotes epithelial cell growth and inflammatory response in the prostate, were identified between the progenitor-like luminal subgroup and both fibroblasts and macrophages. Our single-cell profiling of BPH provides a roadmap for investigating inflammation-linked cell subgroups and highlights a progenitor-like luminal subgroup interacting with other cell groups via MIF that may contribute to the inflammation and cell proliferation phenotype associated with BPH.

overall_design: Prostate tissues from BPH patients undergoing Holmium laser enucleation of the prostate (HoLEP) were dissociated into single cells and then captured and sequenced using the Seq-well single-cell RNA-sequencing platform.

first: Rei

last: Unno

first: Hanbing

last: Song

first: Keliana

last: Hui

first: Yih-an

last: Chen

first: Julia

last: Pham

first: Jean

last: Lee

first: Heiko

last: Yang

first: Franklin

last: Huang

first: Thomas

last: Chi


title: Metformin reduces RAN proteins and rescues molecular and behavioral phenotypes in SCA8 mice

city: Gainesvillle

first: Lisa

last: Romano

state: Florida

address: 2033 Mowry Road

department: Molecular genetics and microbiology

institute: University of Florida

summary: Spinocerebellar ataxia type 8 (SCA8) is a member of a group of dominantly inherited, debilitating neurological diseases caused by CAG•CTG expansions for which there are no effective disease-targeting treatments. RAN translation, which was discovered in SCA8, has previously been shown to occur across CAG and CUG expansion transcripts, making treatments that work for SCA8 potentially relevant to a broader group of diseases, including SCA1, 2, 3, 6, 7, 12, Huntington’s Disease (HD), Fuch’s endothelial corneal dystrophy (FECD), and myotonic dystrophy type 1 (DM1). Additionally, CUG and CAG expansion transcripts have been reported to cause RNA gain-of-function effects. In C9orf72 ALS/FTD mice, we previously showed that metformin reduced RAN protein levels and improved behavior and neurological phenotypes. Using SCA8 BAC transgenic mice as a model for CAG•CTG expansion diseases, we now show that metformin improves ambulatory performance using rotarod, DigiGait, and open-field measures. At the molecular level, metformin-treated mice showed reduced RAN protein levels and improved alternative splicing abnormalities without changing the levels of the expanded RNAs. Metformin-treated mice also showed decreased neuroinflammation, with reduced astrogliosis and fewer activated microglia. These data provide strong preclinical support for testing metformin in clinical trials for SCA8 and potentially the broader group of CAG•CTG repeat expansion disorders.

overall_design: In this study, we sought to determine whether metformin can prevent and/or reverse the behavioral and pathological phenotypes of SCA8 transgenic mice. Because RAN proteins start to accumulate early in the disease, we designed our study by treating female and male SCA8 BAC transgenic mice beginning at the age of 4 weeks, well before the development of behavioral and pathological phenotypes. During the treatment period of 60 weeks, animals were assessed for behavioral defects at 8, 16, 32, and 52 weeks. Final take-downs were done at 60 weeks of age. RNA-seq was runned on brainstem and cerebellum from 4 animal per group, including 4 Non-Transgenic mice treated with water (NT_Water), 4 SCA8 mice treated with water (SCA8_Water) and 4 mice treted with metformin (SCA8_Met).

first: Laura

last: Ranum


title: Super-enhancers reorganization controls re-sensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer [ChIP-seq]

city: Udine

first: Nicolò

last: Gualandi

state: Italy

address: P.le Kolbe, 4

department: Department of Medicine

country: Italy

institute: Università degli studi di Udine

summary:
Epigenetic plasticity and large-scale chromatin remodeling characterize tumor evolution and the emergence of subclones resistant to conventional therapies. Catalytically inactive class IIa HDACs (HDAC4, HDAC5, HDAC7, HDAC9) act as acetyl-lysine readers that form the scaffold for the targeted recruitment of chromatin remodeling complexes, making them very attractive therapeutic targets in the field of oncology.
In this study, we found that HDAC4 is proteasomal degraded in cancer cells impaired in DNA repair by homologous recombination. Genetic screening identified FBXW7 as the E3 ligase responsible for this degradation. FBXW7 loss-of-function mutations are frequently found in patients with colorectal cancer (CRC), and FBXW7 mutation status is associated with the development of resistance to oxaliplatin. Deletion of HDAC4 or its forced degradation with a PROTAC-based compound restored oxaliplatin sensitivity in FBXW7-mutated CRC cells, patient-derived organoids (PDOs) and xenografts, with no effect on DNA damage response activation or DNA platination.
Mechanistically, forced removal of HDAC4 in FBXW7-mutant CRC cells and PDOs treated with oxaliplatin resulted in a deep rearrangement of the super-enhancer landscape, with a dramatic loss of super-enhancers found in oxalipaltin-resistant samples and restoration of certain super-enhancers found in oxaliplatin-sensitive cells. The disassembly of HDAC4 complexes achieved with Tasquinimod partially recapitulated the effects obtained with the PROTAC-based HDAC4 compound, demonstrating the importance of the epigenetic function of HDAC4 in supporting drug resistance.
This study supports HDAC4 as a key mediator of oxaliplatin resistance in FBXW7-mutated CRC and highlights the remodeling of a well-defined repertoire of super-enhancers as part of the process of successful re-sensitization.

overall_design: Chromatin was extracted from HCT-116 cells, WT or KO for FBXW7, and transfected for 48h with esiRNAs directed against CT or HDAC4. Cells were treated or not for the last 24h with OxPt (50 µM). After cross-linking, 50µg chromatin was immunoprecipitated from each samples with 3µg antibody against H3K27ac (Abcam, ab4729) or IgG. After de-crosslinking, chromatin was eluted and subjected to library preparation and sequencing.

first: Vanessa

last: Tolotto

first: Ylenia

last: Cortolezzis

first: Eros

last: Di Giorgio


title: Facile Induction of Immune Tolerance by an Interleukin-2-TGF-β Surrogate Agonist

city: Palo alto

first: Qinli

last: Sun

address: 279 Campus Drive

institute: Stanford University

summary: CD4⁺ regulatory T (Treg) cells are essential for establishing and maintaining immune tolerance. Peripherally induced Tregs (pTregs), which differentiate from mature conventional CD4⁺ T cells in the periphery, complement Tregs generated in the thymus during T cell development by broadening Treg reactivity in response to changing self and the environment. Although both TGF-β and Interleukin-2 (IL-2) synergistically promote functional pTreg development in vitro, their combined roles in inducing pTreg generation in vivo have not been thoroughly characterized and therefore are yet to be exploited for tolerizing immunotherapy. The principal limitation to in vivo use of IL-2 and TGF-β is their pleiotropy and inability to ensure co-delivery of SMAD and STAT signaling to the same cell. To overcome these challenges, we designed an IL-2-TGF-β surrogate agonist by creating a fusion protein between IL-2 and a low-affinity TGF-β mimic agonist derived from a Helminth parasite. This IL-2-TGF-β surrogate agonist was easily expressed and purified and enabled simultaneous cis-activation of both IL-2 and TGF-β signaling specifically in IL-2 receptor-expressing T cells. This IL-2-TGF-β surrogate agonist robustly induced antigen-specific, functional, and stable pTregs in vivo within peripheral lymphoid organs in OVA- or MOG35-55-immunized mice. The induced pTregs phenotypically resemble effector and colonic Rorγt⁺ pTregs, with the potential to efficiently migrate into the gut and suppress intestinal inflammation. Treatment with this agonist effectively quelled immune activation in mouse models of allergen-induced allergic inflammation and self-antigen-driven autoimmune neuroinflammation, portending a strategy for the targeted induction of antigen-specific pTregs in vivo to induce immune tolerance in inflammatory and autoimmune diseases.

overall_design: One million sorted Thy1.1⁺ naïve OT-II cells were adoptively transferred into Thy1.2⁺ Foxp3-GFP recipient mice via retro-orbital intravenous injection. This was followed by six intraperitoneal injections of 100 μg OVA protein combined with 50 pmol of the indicated proteins, administered every other day. On day 11, donor OT-II cells and host Foxp3-GFP⁺ CD4⁺ T cells were sorted from the mLNs of the respective treatment groups and submitted to MedGenome, Inc. for library preparation and RNA sequencing.

first: Masato

last: Ogishi

first: K Christopher

last: Garcia


title: Transcriptomic Insights into Aerobic Exercise-Mediated Attenuation of High-Fat Diet–Induced Muscle Wasting

status: Public on Feb 20 2026

city: Quanzhou

first: Weihao

last: Hong

address: Donghai

institute: Quanzhou Normal University

summary: Chronic consumption of high-fat diet (HFD) induces obesity and metabolic dysfunction and is accompanied by progressive skeletal muscle wasting. Although aerobic exercise is generally considered less effective for maintaining muscle mass, accumulating evidence suggests that it can attenuate HFD-induced muscle wasting. However, the molecular mechanisms underlying this protective effect remain poorly defined. In this study, we investigated the effects of moderate-intensity continuous training (MICT) on HFD-induced muscle wasting and characterized the associated transcriptomic adaptations in the mouse gastrocnemius muscle. Twenty-one weeks of HFD feeding increased body weight and serum glucose levels and induced marked muscle wasting, as evidenced by reduced gastrocnemius muscle index, impaired normalized forelimb grip strength, decreased muscle fiber cross-sectional area, and excessive intramuscular lipid accumulation. These pathological alterations were significantly attenuated by an 8-week MICT intervention. RNA sequencing revealed that HFD predominantly induced a lipid-centered transcriptional program characterized by enhanced fatty acid uptake, trafficking, and β-oxidation. In contrast, MICT predominantly suppressed atrophy-associated genes (Foxo1, Fbxo32, and Trim63), while exerting minimal effects on myogenic genes (Pax7, Myod1, and Myog). Functional enrichment analyses further indicated that MICT modulated signaling pathways related to FoxO, PI3K–Akt, MAPK, and insulin signaling, together with biological processes associated with angiogenesis and calcium signaling. Collectively, these results suggest that MICT mitigates HFD-induced muscle wasting primarily by reprogramming the transcriptome from a lipotoxic, atrophic state toward a more insulin-sensitive, pro-angiogenic profile, with limited myogenic activation.

overall_design: After 1 week of acclimation, 3-week-old male C57BL/6J mice were randomly allocated to four groups: standard chow diet (C), standard chow diet plus MICT (CM), HFD (H), and HFD plus MICT (HM). The dietary intervention was maintained throughout the entire experiment (weeks 1–21). Starting at week 13, mice assigned to the exercise groups completed a 1-week treadmill acclimation phase (10 m/min for 10 min/day, 5 days/week), followed by an 8-week MICT intervention (weeks 14–21). Each session lasted 45 min and was performed 5 days per week, preceded by a 10-min warm-up at 10 m/min. Treadmill speed was progressively increased from 13 m/min (weeks 14–15) to 15 m/min (weeks 16–17), and then to 17 m/min (weeks 18–21). Gastrocnemius muscles were collected for RNA-seq at the endpoint.

first: Jianrong

last: Zheng

first: Yisheng

last: Luan

first: Haibin

last: Yu

first: Yueyun

last: Xu

first: Bing

last: Zhang


title: FOXO1 integrates endothelial hemodynamic, inflammatory and metabolic pathways in atherosclerosis [OSS]

city: New Haven

first: Hanqiang

last: Deng

address: 116 Court Street

institute: Yale University

summary: Atherosclerosis occurs preferentially in regions of disturbed or low fluid shear stress (FSS), whereas physiological laminar FSS protects against disease by suppressing endothelial inflammation. Pro- vs anti-inflammatory programs are associated with glycolysis vs mitochondrial metabolism, respectively. Endothelial cells (ECs) sensing FSS from blood flow regulate these responses, but the underlying mechanisms are poorly understood. The transcription factor Forkhead box protein O1 (FOXO1) is known to regulate endothelial metabolism, yet its role in FSS-regulated endothelial inflammation remains largely unclear. We found that Oscillatory FSS and inflammatory cytokines induce, whereas physiological FSS inhibits FOXO1 nuclear translocation. RNA sequencing revealed that FOXO1 depletion in ECs upregulates the protective flow-responsive transcription factors KLF2/4 and reduces oscillatory FSS-induced inflammatory genes. Inhibition of FOXO1 nuclear translocation by physiological FSS is mediated via a KLF2-CDK2 pathway, with the latter phosphorylating FOXO1 at S249. Artery ECs-specific deletion of FOXO1 significantly reduces atherosclerotic plaque formation in hyperlipidemic mice. Inhibition of glycolysis attenuates OSS-induced FOXO1 nuclear translocation, suggesting a role for metabolic regulation. Notably, treatment with lactate promotes FOXO1 nuclear localization and lactylation, which is mediated by a lactyltransferase AARS1 (Alanyl-tRNA synthetase). These findings identify FOXO1 as a key mediator linking atheroprone flow and endothelial inflammation, suggesting potential new therapeutic targets for treating atherosclerotic cardiovascular disease.

overall_design: Human aortic endothelial cells (HAECs) were transfected with Ctrl (siCtrl) or FOXO1 (siFOXO1) siRNA for 3 days, then subjected to oscillatory shear stress (OSS; 0.5±4 dynes/cm2) for 24 hours. Total RNA was extracted and subjected to RNAseq, n=3 samples for each group.


title: Super-enhancers reorganization controls re-sensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer

overall_design: RNA was extracted from HCT-116 cells, WT or KO for FBXW7, and transfected for 48h with esiRNAs directed against CT or HDAC4 or treated with PROTAC compound #11 directed against HDAC4. Cells were treated or not for the last 24h with OxPt (50 µM).


title: Mapping 3’ untranslated regions reveal compromised alternative polyadenylation in human right ventricle failure

city: Houston,

first: Hari Krishna

last: Yalamanchili

state: TX

address: 1250 Moursund St #1125,

institute: Baylor College of Medicine

summary: Right ventricular failure (RVF) impacts the prognosis of pulmonary arterial hypertension (PAH). Alternative polyadenylation (APA) generates transcript diversity and is implicated in diseases, including left heart failure. However, understanding genome-wide polyadenylation maps in RVF patients with PAH is limited, with no studies investigating RVF-specific APA events. This study mapped 3' untranslated regions (3'UTRs) to explore APA dynamics in RVF development, comparing healthy donors and RVF from patients with PAH.

overall_design: Right ventricular control and failure samples, as well as human cardiac fibroblasts treated with control or CPSF6 siRNA.

first: Rajarajan

last: Thandavarayan

last: Yamalanchili


title: Persistent Activation of Monocytes/Macrophages and Cell Senescence in SIV-Infected Macaques on ART

status: Public on Feb 23 2026

city: New Orleans

first: Xuebin

last: Qin

state: LA

address: 1430 Tulane Avenue

department: Pathology

institute: Tulane University

summary: Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) experience persistent inflammation, immune dysfunction, and premature onset of cardiovascular and aging-related comorbidities. To define the underlying mechanisms, we performed longitudinal transcriptomic profiling in peripheral blood mononuclear cells (PBMCs) from a cohort of simian immunodeficiency virus (SIV)-infected rhesus macaques spanning four key stages: pre-infection, acute infection, short-term ART, and long-term ART. Bulk RNA sequencing revealed dynamic immune remodeling across infection and treatment. Acute SIV infection induced robust antiviral and inflammatory programs, with upregulation of interferon-stimulated genes (ISGs), IL-27, JAK/STAT, and NF-κB signaling, coupled with suppression of T- and B-cell activation pathways. Short-term ART effectively reversed these transcriptional perturbations, restoring adaptive immune gene expression and reducing innate antiviral responses to near-baseline levels. In contrast, chronic SIV infection on long-term ART maintained viral suppression but was characterized by reactivation of innate immune pathways, including TLR2/TLR4/MYD88, NF-κB, and inflammasome (NLRP3/NLRP12, caspase-1) signaling, along with sustained macrophage activation, platelet/coagulation signaling, and senescence-associated secretory phenotype. Protein analyses confirmed persistent CASPASE-1 and NF-κB activation in spleen tissue. Pathologic evaluation of a carotid artery from an SIV-infected, long-term ART–treated macaque revealed macrophage-rich plaques with p21⁺ senescent cells with intraluminal thrombus formation, recapitulating key features of HIV-associated atherogenesis. Together, these findings demonstrate that while ART normalizes acute infection–induced immune dysregulation, chronic SIV infection sustains a chronic, macrophage- and TLR-driven inflammatory state linked to vascular injury and aging process regardless of long-term suppression of viremia. Targeting inflammasome, NF-κB, and senescence pathways may mitigate non-AIDS comorbidities in PLWH.

overall_design: We randomly selected 4 animals from a previous cohort that had longitudinal PBMC samples collected at four key time-points: pre-SIV infection (day 0), 6 weeks post-SIV infection (acute SIV infection), after 2 months of short-term ART, and after one year (12 months and 20 months) of long-term ART, for RNA-seq analyses. This cohort effectively models the major stages of HIV infection in humans: 1) pre-infection, 2) acute HIV infection, 3) HIV infection on short-term ART treatment, and 4) chronic HIV infection on long-term ART treatment as seen in PLWH. Of note, the plasma samples from two of the animals in group 4 chronic HIV infection on long-term ART treatment were collected at two time points (12 months and 20 months), hence adding to 6 samples in that group. To comprehensively profile the dynamic transcriptomic changes in the PBMCs collected before and after SIV infection, with or without ART treatment, we conducted the bulk RNA-seq and performed six pairwise comparisons: 1) acute SIV-infection vs. baseline, 2) acute SIV-infection on short-term ART vs. acute SIV-infection, 3) acute SIV-infection on short-term ART vs baseline, 4) chronic SIV-infection on long-term ART vs acute SIV-infection, 5) chronic SIV-infection on long-term ART vs baseline, and 6) chronic SIV-infection on long-term ART vs chronic SIV-infection on short-term ART.

first: Yilin

last: Chen

first: Xiaofeng

last: Ding

first: Sonalika

last: Ray

first: Siva

last: Thirugnanam

first: Robert

last: Blair

first: Ahmad

last: Saied

first: Sergiy

last: Sukhanov

first: Jay

last: Kolls

first: Woong-Ki

last: Kim

first: Patrice

last: Delafontaine

last: Rappaport

first: Namita

last: Rout


title: Histone deacetylases and cell cycle regulators orchestrate cell identity transitions during Arabidopsis root regeneration

city: Gif-sur-Yvette

first: Bruno

last: Guillotin

address: Bâtiment 630, Avenue des Sciences

department: Biology

country: France

institute: Institute of Plant Sciences of Paris-Saclay - IPS2

summary: The widespread regenerative capacity of plants is mediated by the ability of specialized cells to reprogram their fate, but the sequential cellular states of regenerating plant cells remain an open question. Here, we characterize the trajectory of cellular reprogramming using single-cell RNA/ATAC-seq, imaging, and mutant analysis. The earliest events were dependent on repressive chromatin modification, where Multiome and genetic analysis showed that Class I histone deacetylases (HDACs) HDA9 and HDA19 were needed to shut down old identities and to prevent a runaway stress response. Cell division mediates a second step needed for the acquisition of many new identity markers, where division rates were tuned by DOF transcription factor OBP1 accelerating and SMR5, 7, and 10 decelerating division rates hours later. The results show how plants actively mediate the loss of remnant identities within hours of injury and then tune cell division rates to rapidly reprogram cells to new identities.

overall_design: Arabidopsis root tips were cut at 130um from the tip to induce regeneration. The roots were then collected, uncut (CTR), or at 4h, 9h, 14h, 24h and 36h post cut. Certain replicates involve treatment with TSA, roscovitin and curcumin. Roots were protoplasted and scRNAseq was performed using 10xgenomics 3'UTR kit as per protocol. Data was then processed using CellRanger and Seurat. Additionaly, one dataset was obtained from Arabidopsis root nuclei treated or not with TSA 0 or 2h post cut. Multiome analysis was performed using 10x genomics Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit. Data was then processed using CellRanger and Signac.

first: Ramin

last: Rahni

first: Laura

last: Lee

first: Indie

last: Suresh

first: Brandon

middle: M

last: Gorodokin

first: Graeme

last: Vissers

first: Kenneth

last: Birnbaum


title: Genomic characterization of mouse hindlimb skeletal muscles with divergent slow myofiber content at an embryonic and adult time point [RNA-Seq]

first: Terence

last: Capellini

state: MA

address: 11 Divinity Avenue

institute: Harvard University

summary: Here, we characterize the genomic landscape of four mouse hindlimb muscles that differ in slow myofiber content at two time points (E18.5 and adult) to identify novel enhancers that may underlie the expression of genes involved in myofiber development and physiology. RNA-seq analysis revealed that fast- and slow-biased muscles show divergent patterns of gene regulation beginning at a late embryonic time point and persisting through adulthood. Genes differentially expressed between adult fast- and slow-biased muscles were enriched with biological pathways unique to each myofiber type, with glycolytic pathways characterizing adult fast-biased muscles and mitochondrial biogenesis and lipid metabolism characterizing adult slow-biased muscles. By integrating differential expression analysis (RNA-seq) with differential accessibility analysis (ATAC-seq) we identified twelve conserved, muscle-specific candidate enhancers nearby differentially expressed genes that regulate cell metabolism and the genetic markers of myofiber type. Nine candidate enhancers significantly increased and three significantly decreased luciferase reporter activities in C2C12 cells, highlighting the dynamic role of tissue-specific enhancers and repressors on development and differentiation. However, further validation is needed to see if these enhancers regulate the expression of target genes and the effect on muscle myofiber content. Collectively, these results highlight the importance of conserved, skeletal muscle-specific enhancers on skeletal muscle development and adult myofiber phenotypes and provide additional genomic targets for further validation.

overall_design: Examination of open chromatin regions (ATAC-seq) and differentially expressed genes (RNA-seq) in mouse hindlimb muscles with divergent slow myofiber content at an embryonic (E18.5) and adult (P56) time point.

first: Samantha

last: Queeno

first: Alexander

middle: S

last: Okamoto

first: Kirstin

last: Sterner