title: Sub-cellular System Drift Drives Mosaic Evolution of Mammalian Neurons

city: Philadelphia

first: Junhyong

last: Kim

state: PA

address: 433 South University Ave

department: Biology

institute: University of Pennsylvania

summary: To examine the rate of evolutionary divergence between Mus musculus (C57BL/6) and Rattus norvegicus (Sprague–Dawley) dendritic transcriptome, we generated a rat sister datasets to a previously existing mouse dataset from our lab (GSE115480). We manually separated the dendrites and soma of pirimary rat hippocampal neurons using a micropipette and performed RNA-seq on each subcellular fraction as separate but paired subcellular transcriptomic experiments for each captured cell.

overall_design: 16 individual rat neurons were collected and dissected for a total of 16 pairs of samples (1 soma and 1 dendritic samples per cell) from multiple cell cultures across multiple days.

first: Jean

last: Rosario


title: DUSP2 Suppresses the Chromatin Remodeling BAF Complex to Orchestrate CD8+ T Cell Effector Programming

status: Public on Jul 31 2026

city: Rochester

first: Emilia

middle: R

last: Dellacecca

state: MN

address: 200 First Street SW, Kellen Building 02-102

department: Immunology

country: USA

institute: Mayo Clinic

type: Expression profiling by high throughput sequencing

summary: Effector gene expression in CD8⁺ T cells is tightly controlled at epigenetic and transcriptional levels; however, crucial regulatory signals remain incompletely understood. In this study, we identify Dual Specificity Phosphatase 2 (DUSP2) as a key epigenetic modulator of effector CD8⁺ T cell state, by elucidating inhibition of BAF-mediated chromatin opening by DUSP2. Induced downregulation of DUSP2 in human CD8+ T cells enhanced cytotoxicity and effector phenotypes by increasing chromatin accessibility through upregulation of BAF subunits, such as SMARCA4, and permitting binding of ETS1 to BAF subunit gene loci and those essential for effector programs. Conversely, during chronic activation, DUSP2 knockout in murine CD8+ T cells predisposed terminally differentiated effector cells to exhaustion. These findings uncover a previously unrecognized role of DUSP2 in the management of the chromatin landscape in CD8+ T cells and the epigenetic fine-tuning of their functionality, highlighting DUSP2 as a promising therapeutic target for T cell-based immunotherapy.

overall_design: Bulk RNA-sequencing of splenic CD8+ T cells from Dusp2 CD8+ T cell conditional knockout mice or Dusp2-floxed-control mice at rest or after anti-CD3/CD28 bead-based ex-vivo activation for 24-hours.

first: Jacob

middle: B

last: Hirdler

first: Whitney

last: Barham

first: Ying

last: Li

first: Joanina

middle: K

last: Gicobi

first: Yiyi

last: Yan

first: Haidong

last: Dong


title: DUSP2 Suppresses the Chromatin Remodeling BAF Complex to Orchestrate CD8+ T Cell Effector Programming [RNA-seq]

overall_design: Bulk RNA-sequencing of CD8+ T cells from the peripheral blood of healthy human donors with transfection of DUSP2-targeting silencing RNA (siRNA) or negative control siRNA at rest or after anti-CD3/CD28 soluble antibody-based ex-vivo activation for 24-hours.


title: Immunometabolic Endotypes Define Distinct Clinical Trajectories in Type 2 Diabetes [bulk RNA-seq]

city: Paris

first: Nicolas

last: Venteclef

address: 156 rue de Vaugirard

country: France

institute: Institut Necker Enfants Malades, INSERM U1151

summary: Type 2 diabetes (T2D) exhibits substantial heterogeneity, yet current classifications do not fully capture its immune complexity. Here, we provide transcriptomic datasets from circulating CD14⁺ monocytes (bulk RNA-seq) and peripheral blood mononuclear cells (PBMCs, single-cell RNA-seq) derived from newly diagnosed T2D patients. Using neutrophil, lymphocyte, and monocyte counts, patients were stratified into four immune endotypes via unsupervised clustering: Severe Inflammatory Diabetes (SIND), Mild Inflammatory Diabetes (MIND), Lymphocyte Rich Diabetes (LYRD), and Lymphocyte Deficient Diabetes (LYDD). Bulk and single-cell transcriptomic analyses reveal endotype-specific immune signatures, including selective expansion of CCR2hi and CD39hi classical monocytes in SIND, enrichment of monocyte states associated with chemotaxis and myeloid activation, and altered adaptive immune programs. These profiles were modulated by IL-1β antagonism and bariatric surgery–induced remission. This dataset provides a resource for exploring the immune heterogeneity of T2D.

overall_design:
Bulk RNA-seq (CD14⁺ monocytes)

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

first: Bao Tran

last: Vuong

first: Chloé

last: Delepine

first: Marc

last: Diedisheim

first: Amélie

last: Bonnefond


title: Thalidomide Reverses Sporadic Arteriovenous Malformation in the Central Nervous System

city: Beijing

first: Hongyun

last: Zhang

state: Dr

address: 45 Changchun ST

country: China

institute: CCMU

summary: Sporadic arteriovenous malformations of the central nervous system (CNS-AVMs) are caused by somatic activating mutations of KRAS within endothelial cells (ECs) of the brain and spinal cord. There is no approved drug for this disease because the lack of a clinically representative animal model has hindered drug discovery. Here, we developed a novel mouse model of sporadic brain AVM (BAVM) induced by intracerebral injection of AAV-BR1-KRASG12V. This model faithfully recapitulates the clinical manifestations, radiology, pathology, and transcriptomic profiles of human sporadic BAVM. Connectivity Map database analysis revealed thalidomide as a promising therapeutic. Preclinical experiments revealed that thalidomide can restore mural cell coverage with downregulating Angiopoietin 2 (ANGPT2) in ECs and inhibiting BAVM progression. This effect reduced hemorrhage and prolonged the survival of mice with BAVM. We then administered thalidomide to 30 patients with sporadic CNS-AVMs. Over a median treatment duration of 7.3 months, AVM lesions regressed in 60.7% of patients, while symptoms improved in 10.7%. Biopsies demonstrated that thalidomide increased mural cell coverage and decreased ANGPT2 expression in ECs within AVM lesions. In summary, we established a representative model of sporadic BAVM and provided promising evidence supporting the therapeutic potential of thalidomide for sporadic CNS-AVMs.

overall_design: Transcriptomic analysis revealed the gene expression characteristics of KRAS-mutant brain AVM mouse models established using different induction methods (Model 1/Control and Model 2/Control), as well as the effects of thalidomide on gene expression in brain AVM mice.

first: Jiaxing

last: Yu

first: Tao

last: Hong


title: Metabolic Plasticity Underlies Ferroptosis Resistance Driven by Mutant p53 in Pancreatic Ductal Adenocarcinoma

city: Verona

first: Alessandra

last: Fiore

state: VR

address: Str. le Grazie, 8

country: Italy

institute: University of Verona

summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by late diagnosis, rapid progression, and resistance to conventional therapies. Mutations in the tumor suppressor gene TP53 are prevalent in this cancer and have been associated with gain-of-function activities that promote tumor survival. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a potential therapeutic vulnerability. However, the influence of mutant p53 on ferroptosis susceptibility remains poorly understood.We employed isogenic pancreatic cancer cell models, including CRISPR-Cas9-mediated TP53 knockout and transient overexpression of common mutant TP53 variants, to examine ferroptosis sensitivity. Cell viability, reactive oxygen species accumulation, lipid peroxidation, mitochondrial integrity, and metabolic profiling were assessed following treatment with ferroptosis inducers. Transcriptional changes were analysed by RNA sequencing, and functional contributions of glycolysis and mitochondrial respiration were evaluated using metabolic flux assays. Pharmacological reactivation of wild-type p53 was tested in combination with ferroptosis inducers in vitro and in orthotopic murine models.Deletion of mutant TP53 sensitized pancreatic cancer cells to ferroptosis, accompanied by increased oxidative stress, lipid peroxidation, and mitochondrial dysfunction. Mutant TP53 expression preserved mitochondrial integrity and sustained bioenergetic flexibility under ferroptotic stress. Transcriptomic analyses revealed a multi-layered adaptive program, including upregulation of antioxidant and metabolic genes, and activation of PI3K–AKT signaling, which is associated to a selective glycolytic shift to maintain ATP levels. Functional modulation confirmed that glucose supplementation enhanced, whereas glycolytic inhibition impaired, survival under ferroptotic conditions in mutant TP53-expressing cells, but not in TP53 KO cells. Pharmacological reactivation of wild-type p53 disrupted this adaptive network, abrogating glycolytic reprogramming and significantly increasing ferroptotic cell death both in vitro and in vivo. Mutant p53 orchestrates transcriptional and metabolic plasticity that confers ferroptosis resistance in pancreatic cancer. Reactivating wild-type p53 in combination with ferroptosis induction overcomes this resistance, highlighting a therapeutically actionable vulnerability and supporting the development of combinatorial strategies for this aggressive malignancy.

overall_design: RNA-seq profilying of PANC-1 and TP53 KO PANC-1 cells after ferroptosis induction with RSL3

first: Adriana

last: Celesia

first: Antonino

last: Aparo


title: Patient-derived airway organoids from BAL fluid model injury and therapy responses in neonatal bronchopulmonary dysplasia [NGFR]

first: Abiud

last: Cantu

state: Pennsylvania

address: 3615 Civic Center Blvd

department: Neonatology

institute: Children's Hospital of Philadelphia

summary: Lung tissue from fetal and neonatal lung samples is tough to obtain, and capturing cells from a living patient with evolving or established disease is very challenging.  We hypothesized that airway organoids derived from BAL samples from intubated preterm neonates with established BPD will recapitulate the epithelial heterogeneity seen in human airways and can be used for studying injury and therapy responses in vitro. BPD patient BAL-derived airway organoids exhibited cellular heterogeneity consistent with that observed in the human airway. BAL sample-derived airway organoids from patients with established BPD contain basal cell progenitors and a spectrum of differentiated epithelial subtypes, including secretory, ciliated, PNECs, and hillock cells. Hyperoxia exposure and treatment with dexamethasone caused significant cellular transcriptional changes and highlighted biological pathways, both known and novel. Sex as a biological variable modulates the response of the BAL-derived airway organoid to hyperoxia exposure and treatment with dexamethasone. We also validated our findings in an independent dataset from human BPD lung samples. BAL-derived human lung organoids represent a cutting-edge model that bridges a critical gap in BPD research. They combine the advantages of being patient-specific and capturing developmental lung biology, with the experimental flexibility of an in vitro system.

overall_design: Bulk RNA sequencing analysis comparing NGFR-positive and NGFR-negative cell populations sorted from patient-derived airway organoids established from bronchoalveolar lavage (BAL) fluid of intubated preterm neonates with established bronchopulmonary dysplasia (BPD). NGFR (nerve growth factor receptor) serves as a marker for basal cells in airway epithelium. The experiment aims to characterize transcriptional differences between basal cell-enriched (NGFR+) and other epithelial cell populations (NGFR-) to understand cellular heterogeneity in BAL-derived airway organoids.

first: Shilpa

last: Sonti

first: Manuel

last: Cantu Guttierez

first: Connor

last: Leek

first: Phinzy

last: Pelton

first: Erik

last: Jensen

first: Krithika

last: Lingappan


title: Patient-derived airway organoids from BAL fluid model injury and therapy responses in neonatal bronchopulmonary dysplasia [Oxygen Sex Comparisons]

overall_design: Bulk RNA sequencing analysis of patient-derived airway organoids from bronchoalveolar lavage (BAL) fluid of intubated preterm neonates with established bronchopulmonary dysplasia (BPD) exposed to hyperoxia versus room air conditions. The study compares organoids exposed to 85% oxygen (hyperoxia) for 48 hours versus room air controls, with samples stratified by biological sex (male and female patients). The experiment aims to characterize transcriptional responses to hyperoxic injury and identify sex-specific differences in oxidative stress response in developing airway epithelium.


title: Patient-derived airway organoids from BAL fluid model injury and therapy responses in neonatal bronchopulmonary dysplasia [Oxygen vs Room Air]


title: Myeloid PINK1 represses mtDNA release and immune signaling that impacts neuronal pathology in patient-derived idiopathic PD models

city: Montreal

first: Jo

middle: Anne

last: Stratton

state: Quebec

address: 3801 University street

department: Neurology and Neurosurgery

country: Canada

institute: McGill University

summary: Parkinson’s disease (PD) is a neurodegenerative disorder marked by the development of cardinal motor deficits preceded by a protracted prodromal period of non-motor symptoms often involving the gastrointestinal (GI) tract. There is an emerging consensus that both the peripheral immune system and local neuroinflammation play key roles in the etiology of PD. We previously demonstrated a critical function for the Parkinson’s related proteins PINK1 and Parkin as repressors of the innate to adaptive immune response in cultured cells and mouse models of infection. However, it remained unclear whether these processes were conserved in patient-derived models, and precisely how immune signaling may ultimately drive the death of dopaminergic neurons. Here we show that GI infection of PINK1 knockout (KO) mice triggered acute neurodegeneration which was evident early in the enteric nervous system. Treating wild type enteric or dopaminergic neurons with conditioned medium from immune-stimulated PINK1 KO macrophages was sufficient to promote neuronal disruption in both mouse and human neurons in vitro. Within immune-activated macrophages, we reveal that loss of PINK1 led to an enhanced release of mitochondrial DNA (mtDNA) within mitochondrial derived vesicles, leading to the activation of cGAS/STING pathways. These changes were seen in both mouse/human in vitro models and in PD patient-derived primary macrophages. Notably, pharmacological modulation using a PINK1 activator with high therapeutic potential attenuated pro-inflammatory profiles elicited by the mtDNA-dependent STING/NF-κB pathway in idiopathic patient-derived macrophages. Ultimately, our study lays the foundation for understanding PINK1-related peripheral macrophage mechanisms in idiopathic PD and provides a target for further development to treat the disease at early stages.

overall_design: Wild type and PINK1 KO peripheral myeloid cells derived from human iPSCs were treated with interleukin 1-beta (IL-1b) and lipopolysaccharide (LPS) for 24 h. Cells were then harvested and analyzed using scRNAseq.

first: Recinto

last: Sherilyn Junelle

first: Adam

last: MacDonald

first: Shobina

last: Premachandran

first: Lin

last: Liu

first: Armin

last: Bayati

first: Lilia

last: Rodriguez

first: Mai

last: Nguyen

first: Florence

last: Petit

first: Sriparna

last: Mukherjee

first: Julien

last: Larmanjat

first: Alexis

last: Allot

first: Moein

last: Yaqubi

first: Peter

last: McPherson

first: Thomas M.

last: Durcan

first: Samantha

last: Gruenheid

first: Louis-Eric

last: Trudeau

first: Janelle

last: Drouin-Ouellet

first: Heidi M

last: McBride

first: Jo Anne


title: Functional Proteomic Analysis of HT-29 Cells Treated with MV-GFP, Triptolide, or Combination Using RPPA

city: miami

first: RIMPI

last: KHURANA

state: FL

address: Room 6112B, Rosenstiel Medical Science Building (RMSB),1600 NW 10th Avenue

institute: University of miami

summary: Reverse Phase Protein Array (RPPA) analysis was performed on HT-29 cells to evaluate the effects of vehicle, MV-GFP (MOI 0.5), Triptolide (6.25 nM), and their combination on protein expression. Protein lysates were collected after 48 hours of treatment. RPPA was performed at the MD Anderson Cancer Center RPPA Core Facility. Differential protein expression was analyzed using the limma R package (v3.26.9), with p < 0.05 and FDR < 0.2.

overall_design: HT-29 cells were cultured and treated in vitro with four conditions: vehicle (control), MV-GFP, Triptolide, and MV-GFP + Triptolide. Three biological replicates per condition were analyzed using RPPA to quantify protein expression changes across multiple signaling pathways.

first: Valery

last: Chavez

first: Melissa

last: Montero

first: Ngoc

middle: H

last: Tran

first: Carolina

middle: M

last: Mendes

first: Yuguan

last: Ban

first: Rimpi

last: Khurana

first: Michelle

last: Ceccarelli

first: Jaime

last: Merchan


title: Patient-derived airway organoids from BAL fluid model injury and therapy responses in neonatal bronchopulmonary dysplasia [Dexamethasone]

first: Abiud

last: Cantu

overall_design: Bulk RNA sequencing analysis of patient-derived airway organoids from bronchoalveolar lavage (BAL) fluid of intubated preterm neonates with established bronchopulmonary dysplasia (BPD). The study compares organoids treated with dexamethasone (250 ng/ml for 24 hours) versus vehicle control, with samples stratified by biological sex (male and female patients). The experiment aims to characterize transcriptional responses to glucocorticoid treatment and identify sex-specific differences in therapeutic response in developing airway epithelium.

first: Shilpa

last: Sonti

first: Manuel

last: Cantu Guttierez

first: Connor

last: Leek

first: Phinzy

last: Pelton

first: Erik

last: Jensen

first: Krithika

last: Lingappan


title: In vitro treatment of HT-29 human colorectal cancer cells and NanoString nCounter analysis

summary: HT-29 human colorectal cancer cells were treated in vitro with Vehicle control (Ctrl), MV-GFP (GFP), Triptolide (TRP), or MV-GFP + TRP (Combo). Three biological replicates were performed per treatment. RNA was extracted using NanoString protocols and analyzed with the nCounter Human Tumor Signaling 360 panel. RCC files for each replicate are provided as raw data. Data were processed using nSolver 4.0 Advanced Analysis module with standard normalization and Benjamini–Hochberg correction.

overall_design: Experimental design includes 4 treatment groups (Ctrl, GFP, TRP, Combo) with 3 biological replicates each. Raw data are RCC files. Data processing includes normalization and statistical analysis in nSolver 4.0.


title: The impact of diethyl phthalate (DEP) on metabolism-related diseases

city: Changzhou

first: Yuancheng

last: Shao

address: No. 68, Gehu Middle Road, Wujin District, Changzhou City

institute: Changzhou No 2 People’s Hospital, the Affiliated Hospital of Nanjing Medical University

summary: Phthalate ester plasticizers (PAEs) , common environmental pollutants, are linked to metabolic disorders like obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH), but their multi-target molecular mechanisms remain unclear.

overall_design: AML12 is a mouse hepatocyte cell line, while iWAT is a mouse white adipocyte cell line. Once the iWAT and AML12 cells reached confluency , they were stimulated with 50uM DEP for 48h.


title: MODULATION OF VIRUS–TUMOR-STROMAL INTERACTIONS BY MINNELIDE ENHANCES SYSTEMIC DUAL TARGETED MEASLES VIROTHERAPY IN BRAF-MUTANT COLORECTAL CANCER

first: RIMPI

last: KHURANA

summary:
Background. Oncolytic viruses represent promising cancer biotherapies due to their ability to selectively lyse tumor cells and stimulate anti-tumor immune responses. However, their long-term efficacy as single agents is inconsistent, underscoring the need for virus-drug combinations to improve outcomes. This study evaluates the effects and mechanisms of triptolide and minnelide in enhancing measles virus oncolysis in human colorectal cancer (CRC) models.
Methods. The in vitro effects of CD46 targeted (MV-GFP) and dual targeted (MV-CD46-muPA) oncolytic MV,  alone and with triptolide were assessed in human CRC cell lines. Mechanistic studies included gene expression analysis, functional proteomics, and western blotting. In vivo efficacy of MV-CD46-muPA combined with minnelide was evaluated in HT-29 and HCT-116 xenografts. Biological effects were further characterized using transcriptomic profiling (RNA-seq), targeted gene expression (NanoString), and histological analysis .
Results. Triptolide enhanced MV mediated oncolysis in vitro, particularly in BRAF mutant CRC cell lines, and modulated cancer pathways including AKT, autophagy, apoptosis and metabolism. In vivo, minnelide significantly improved the efficacy of systemically administered MV-CD46-muPA in human CRC xenografts, with greater effects in BRAF mutant (HT29) models. The combination modulated cell cycle, metabolism, and survival associated genes, promoted apoptosis, and improved intratumoral viral distribution. These molecular effects resulted in reduced tumor cell proliferation (Ki67), decreased angiogenesis (CD31) and increased apoptosis (TUNEL) relative to single agents.
Conclusion. Triptolide and minnelide synergistically enhance the antitumor efficacy of oncolytic measles virus in colorectal cancer, particularly in BRAF mutant tumors through modulation of survival, metabolism and stromal pathways, together with improved viral distribution. These findings underscore the innovative potential of this virus-drug combination and support further translational development for CRC and other malignancies.

overall_design:
Sample Source and Treatments:
HT-29 xenograft tumors and HT-29 cell lines were used for RNA sequencing and targeted gene expression analysis. Treatments included:
Control (vehicle)
Oncolytic measles virus (MV)
Minnelide (TRP derivative)
Combination of MV and Minnelide
RNA Sequencing – Read Processing and Alignment:
RNA was extracted from xenograft tumor samples.
Sequencing reads were processed using Xenome to separate host and graft sequences.
Reads were aligned to the human reference genome using STAR aligner (v2.7.11b).
Normalization and Differential Gene Expression Analysis:
Raw counts were normalized using variance stabilizing transformation (VST).
Differentially expressed genes (DEGs) were identified using DESeq2, comparing:
Control vs MV
Control vs Minnelide
Control vs Combination (MV + Minnelide)
DEGs were considered significant with adjusted p-value < 0.05 and |log2 fold change| ≥ 1.
Benjamini-Hochberg method was used to control the false discovery rate (FDR).
Gene Set Enrichment Analysis (GSEA):
Pathway-level changes were assessed using clusterProfiler.
Hallmark gene sets (H), canonical pathways (C2: CP), and Gene Ontology terms (C5) from MSigDB were used.
Genes were ranked by log2 fold change (combination vs control) and aggregated by gene symbol.
Enrichment was evaluated using normalized enrichment scores (NES) and adjusted p-values.
Pathways with positive NES were considered upregulated; negative NES were considered downregulated.
Ingenuity Pathway Analysis (IPA):
DEGs from DESeq2 were further analyzed using QIAGEN Ingenuity Pathway Analysis.
Canonical pathways, diseases/functions, and gene networks were identified.
Z-scores were calculated to predict activation or inhibition of biological functions.
Targeted Gene Expression Analysis (NanoString):
RNA from HT-29 cells and xenograft tumors was analyzed using nCounter XT Human Tumor Signaling 360 panel.
100 ng RNA per sample was hybridized for 16 hours and scanned in high sensitivity mode.
Raw data were processed in nSolver 4.0 and analyzed using the Advanced Analysis module.
Data were normalized against housekeeping genes, and differentially expressed genes were identified with p<0.05 (Benjamini-Hochberg correction).
Heatmaps were generated for significant genes and pathway-defined gene sets.


title: Patient-derived airway organoids from BAL fluid model injury and therapy responses in neonatal bronchopulmonary dysplasia [BAL Organoids Single Cell]

overall_design: Single-cell RNA sequencing analysis of patient-derived airway organoids established from bronchoalveolar lavage (BAL) fluid collected from intubated preterm neonates with established bronchopulmonary dysplasia (BPD). The study includes organoids from both male and female patients to investigate cellular heterogeneity and sex-specific differences in airway epithelial cell populations. Organoids were cultured under standard conditions and analyzed to characterize the spectrum of differentiated epithelial subtypes.


title: The FOSB-IGFBP5-IGF-1 Axis: A Novel Regulatory Pathway that Suppresses Prostate Cancer Growth

city: Guangzhou

first: Jun

last: Huang

state: Dr.

address: the Fifth Affiliated Hospital, Southern Medical University, 566 Congcheng Avenue, Conghua District, Guangzhou 510900, P.R. China

department: Department of Urology

summary: While the functions of activator protein-1 (AP-1) family transcription factors in prostate cancer (PCa) are well researched, the specific role and mechanisms of FOSB in PCa progression are poorly understood. Here, we aimed to elucidate the precise role of FOSB in PCa and its underlying molecular mechanisms.

overall_design: RNA-seq profling of negative control (OE-NC) vector and their overexpression  derivatives (OE-FOSB) in 22RV1 cells, as well as negative control (sh-NC) vector and their knockdown (sh-FOSB) in PC3 cells.

first: Shengdong

last: Ge

first: Linglan

last: Zhao

first: Xianlu

last: Song

first: Qu

last: Li

first: Xiaofeng

last: Liu

first: Wenjun

last: Tang

first: Tao

last: Wang

first: Qing

first: Shanchao


title: H3K9ac ChIP-seq profiling of wild-type and Slc31a1 conditional knockout mouse bone marrow stromal cells

city: Changchun

first: Yuhang

last: Jiang

state: Jilin

address: No.461 Xinjiang Road

department: Institute of Translational Medicine

institute: The First Hospital of Jilin University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Age-associated bone loss is largely driven by impaired osteoblast generation from bone marrow stromal cells (BMSCs), but the metabolic and epigenetic mechanisms that regulate osteogenic commitment remain incompletely understood. This study identifies SLC31A1-mediated copper uptake as a cell-intrinsic metabolic checkpoint required for BMSC osteogenic differentiation and skeletal integrity. Mesenchymal lineage-specific Slc31a1 deletion impaired bone formation and BMSC osteogenesis and caused Slc31a1-deficient BMSCs to accumulate in an ID1-high progenitor-like state. To investigate the epigenetic mechanism underlying this phenotype, H3K9ac ChIP-seq was performed in wild-type and Slc31a1 conditional knockout mouse BMSCs. The analysis revealed increased H3K9ac enrichment in Slc31a1-deficient BMSCs, including enhanced H3K9ac signal at the Id1 locus, supporting a model in which SLC31A1-dependent copper uptake maintains mitochondrial complex IV integrity and NAD+ homeostasis to enable SIRT1-dependent epigenetic repression of Id1 during osteogenic commitment.

overall_design: H3K9ac ChIP-seq was performed on primary mouse bone marrow stromal cells (BMSCs) isolated from wild-type control mice and mesenchymal lineage-specific Slc31a1 conditional knockout mice. The experimental comparison was designed to determine how loss of SLC31A1-mediated copper uptake alters genome-wide histone H3 lysine 9 acetylation in BMSCs. Chromatin from WT and Slc31a1 cKO BMSCs was immunoprecipitated using an anti-H3K9ac antibody, with corresponding input DNA used as sequencing and peak-calling control. H3K9ac enrichment profiles were compared between WT and Slc31a1 cKO BMSCs, and signal distribution around transcription start sites and at the Id1 locus was visualized to assess genotype-dependent changes in chromatin acetylation.


title: DTMB mitigates diet-induced metabolic dysfunction-associated steatohepatitis by targeting inflammation and lipid metabolism

city: Pohang-si

first: Jae

last: Lee

address: 77 Cheongam-ro, Nam-gu

country: South Korea

institute: POSTECH

summary: Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced stage of metabolic dysfunction-associated steatotic liver disease (MASLD), and is characterized by steatosis, inflammation, and fibrosis. Without effective treatment, MASH can progress to cirrhosis and hepatocellular carcinoma. Despite recent therapeutic advances, there remains an unmet need for agents that address both chronic inflammation and metabolic dysfunction. Here, we investigate the effects of DTMB, a peroxisome proliferator-activated receptor gamma (PPAR-γ)-modulating compound, in multiple diet-induced models of MASLD and MASH. DTMB treatment was associated with reduced hepatic inflammation, accompanied by suppression of NF-κB/NLRP3 inflammasome-related signaling and attenuation of hepatic steatosis, alongside increased adipose triglyceride lipase (ATGL) expression. Notably, unlike full PPAR-γ agonists, DTMB exerts these beneficial effects without causing weight gain. Collectively, our study highlights the promising protective effect of DTMB as a selective PPAR-γ modulator for treating metabolic dysfunction-associated liver disease.

overall_design: RNA-seq profiling of liver tissues from mice subjected to normal diet (ND), high-fat diet (HFD), or methionine-choline-deficient (MCD) diet and treated with either vehicle or DTMB.

first: Eunji

last: Oh

first: Sungji

last: Cho

first: Jeong-Hwa

last: Kang

first: Seung-Hee

last: Gwak

first: Won-Sik

last: Shin

first: Suhyun

last: Yoon

first: Jongshin

last: Kim

first: Kyong-Tai


title: Profiling of histone modifications reveal tumor microenvironment-acquired super-enhancer regulates progression of esophageal squamous cell carcinoma

city: SHANTOU

first: Dajia

address: No. 22 Xinling Road

institute: Shantou University Medical College

summary: Genomic and proteomic studies have advanced our understanding of esophageal squamous cell carcinoma (ESCC) biology and pathogenesisGenomic and proteomic studies of esophageal squamous cell carcinoma (ESCC) have advanced our understanding of the biology and pathogenesis of the disease. However, the histone modification landscape inprofile of ESCC remains poorly characterized, especially from human clinical samplesunderstood. Here, we performed comprehensive histone modification profiling of paired samples from 122 ESCC patients, identifying numerous aberrantly expressed histone modification sitesand identified a number of modification sites that are aberrantly expressed in ESCC. Most of these alterations correlate with patient survivalMost of these differentially expressed histone modification sites are associated with survival in ESCC patients. In particular, H3K27ac is aberrantly expressed in tumor tissue and stroma and its high expression is significantly correlated with poor prognosis of ESCC patients. We analyzed the H3K27ac ChIP-seq data for primary ESCC tumor tissues and ESCC cell lines and identified hundreds of altered putative super-enhancers (SEs) in ESCC tissues respectively relative to ESCC cell lines. Moreover, these differential SEs contribute to the transcriptomic aberrations in ESCC tissues. Genes regulated by ESCC tissue- gained SEs are highly expressed in ESCC tissues compared to ESCCthan in cell lines and are mostly enriched in microenvironment-related pathways. We definerefer to these SEs as tumor microenvironment-acquired super-enhancers (TMEA-SEs). Through integrative analysis of ChIP-seq, RNA-seq, scRNA-seq and ATAC-seq data, we identified a TMEA-SE activated in cancer-associated fibroblasts (CAFs) and found that IL1R1 is directly regulated by this TMEA-SE.   We demonstrated that IL1R1 activation can affect CAFs to promotes ESCC cells migration and invasion via CAFs. Collectively, our findings these observations reveal that a critical oncogenic mechanism in ESCC whereby TMEA-SE drive malignancy by activating IL1R1 in CAFs.

overall_design: We performed ATAC-seq on tumor tissues from four esophageal cancer patients, primary fibroblasts derived from esophageal cancer patients, and three esophageal cancer cell lines. For each group, 5 × 10^5 cells or nuclei were used. The aim was to compare chromatin accessibility between esophageal cancer tumor tissues, fibroblasts, and esophageal cancer cell lines.

first: Liu

last: Peng

first: Yi-Meng

last: Zhang

first: Xiong-xing

last: He


title: SETDB2 mitigates podocyte dysfunction in diabetic kidney disease through epigenetic silencing of SMAD3 [MPC5-RNA-Seq]

first: Lanfang

state: State...

address: China-japan Friendship Hospital

institute: China-japan Friendship Hospital

summary: Podocyte dysfunction represents both an early pathological hallmark and a key driver of proteinuria in diabetic kidney disease (DKD); however, the epigenetic mechanisms underlying this process remains poorly defined. Here, we identify the histone methyltransferase SETDB2 as a pivotal epigenetic suppressor of podocyte dysfunction and DKD progression. Glomerular SETDB2 expression is markedly reduced in both DKD patients and mouse models, showing an inverse correlation with disease severity. Podocyte-specific SETDB2 deficiency exacerbates podocytes dysfunction and accelerates DKD progression, whereas its overexpression exerts renal protective effects. Mechanistically, SETDB2 directly enhances H3K9 trimethylation at the Smad3 promoter, thereby repressing SMAD3 expression and activation, ultimately preserving podocyte function. Notably, we identify TCF21, a transcription factor downregulated in DKD, as a direct upstream regulator of Setdb2 expression via promoter binding and transcriptional activation. Collectively, these findings establish SETDB2 as a key regulator of podocyte integrity and a promising therapeutic target for DKD.

overall_design: To unmask the regulatory mechanism of SETDB2 in podocyte dysfunction, RNA sequencing was performed in Setdb2-knockout (Setdb2KO) and Setdb2 wild-type (Setdb2WT) MPC5 cells. (n=3 per group)

first: Shimin

first: Qi

last: Jin

first: Wenge

first: Liang

first: Lihong


title: SETDB2 mitigates podocyte dysfunction in diabetic kidney disease through epigenetic silencing of SMAD3 [Glomeruli RNA-Seq]

last: Li

overall_design: To investigate the transcriptional profile of HMTs in DKD, we performed RNA sequencing on  isolated glomeruli from DKD mice . (n=3 per group)


title: SETDB2 mitigates podocyte dysfunction in diabetic kidney disease through epigenetic silencing of SMAD3

overall_design: To unmask the regulatory mechanism of SETDB2 in podocyte dysfunction, CUT&Tag was performed with H3K9me3 and SETDB2 antibody in Setdb2-knockout (Setdb2KO) and Setdb2 wild-type (Setdb2WT) MPC5 cells .

last: Liu


title: SETDB2 mitigates podocyte dysfunction in diabetic kidney disease through epigenetic silencing of SMAD3 [Conditional knockout mice-Glomeruli-RNA-Seq]

overall_design: To investigate the mechanisms by which podocyte SETDB2 contributes to DKD progression, we performed RNA sequencing on isolated glomeruli from Cre+/Setdb2fl/fl and Cre-/Setdb2fl/fl mice . (n=3 per group)


title: Chromatin Accessibilty and Gene Expression of Frontotemporal dementia-associated Drosophila knock-in models

city: Portland

first: Andrew

last: Adey

state: OR

address: 3181 S.W. Sam Jackson Park Rd, RHH, L103

department: MMG

institute: Oregon Health & Science University

summary: Frontotemporal dementia (FTD) is a neurodegenerative disease associated with mutations in the microtubule binding protein Tau. The clinical presentation of FTD is heterogeneous with patients exhibiting parkinsonism, dementia, atrophy in the temporal lobes, and personality changes. Treatments are limited to mitigating the behavioral changes associated with FTD as the underlying mechanisms causing the disease are still unclear. Recent work in model systems and post-mortem tissue has shown that expression of FTD-associated Tau leads to epigenetic modifications that alter gene expression. We therefore used recently generated Drosophila knock-in models of FTD and single-cell sequencing techniques to identify chromatin accessibility and gene expression changes that are caused by specific FTD-associated Tau mutations. Comparing flies expressing wildtype human Tau (hTauWT) to flies expressing disease-associated mutant hTau (hTauK369I, hTauV337M, or hTauP301L) revealed differentially accessible regions in all cell populations, and notably many in the pericerebral fat body. One of them, Formin homology 2 domain containing (Fhos), was increased in accessibility specifically in the hTauK369I knock-in and this correlated with increased mRNA levels of Fhos. To determine a role of increased Fhos levels in FTD-associated phenotypes, we overexpressed Fhos specifically in the fat body. Overexpression of Fhos induced behavioral phenotypes in hTauK369I and, at a later age in the wildtype background and in hTauWT. In contrast, reducing Fhos levels induced phenotypes in hTauWT but had no effect on hTauK369I expressing flies. Together this supports that increased Fhos levels in the fat body could promote detrimental effects in hTauK369I.

overall_design: We used Single-cell Combinatoral Indexing of Accessible Chromatin (sciATAC-seq) to profile chromatin accessibility of Drosophila melanogaster model of Frontotemporal dementia (FTD) associated mutations (K369I, P301L, V337M). We used single-nuclei RNA-seq with the 10x Genomics platform to profile gene expression of Drosophila melanogaster model of Frontotemporal dementia (FTD) (K369I). CRISPR was used to create Drosophila knock-in FTD models by replacing the Drosophila tau with the human Tau gene in either the wildtype or mutated sequence. Comparing flies expressing wildtype human Tau (hTauWT) to flies expressing disease-associated mutant hTau (hTauK369I, hTauV337M, or hTauP301L) revealed differentially accessible regions and gene expression in all cell populations in the adult head.

first: Doris

last: Kretzschmar

first: Eve

last: Lowenstein


title: SETDB2 mitigates podocyte dysfunction in diabetic kidney disease through epigenetic silencing of SMAD3 [Kidney RNA-Seq]

overall_design: To investigate the transcriptional profile of HMTs in DKD, we performed RNA sequencing on whole kidneys  from DKD mice . (n=3 per group)

last: Jiang


title: Single-cell immune profiling of third trimester pregnancies defines importance of chemokine receptors and prevalence of CMV-induced NK cells in the blood and decidua

city: Melbourne

first: Shihan

state: Victoria

address: 792 Elizabeth Street

country: Australia

institute: Peter Doherty Institute, University of Melbourne

summary: Successful pregnancy requires a well-coordinated adaptation of the immune system. To understand the immunological landscape in pregnancy, we performed a multiplexed cell-surface proteome screen of >350 markers on NK cells, CD4+, CD8+ and γδ T cells, B cells and monocytes in pregnant peripheral blood, cord blood and decidua, and scRNAseq, including 130 CITE-seq antibodies, on NK cells from the blood and decidua. In pregnancy, NK cells had increased AREG, SOCS1, HLA-D family gene expression, and increased CCR5 and HLA-DR, and decreased CD9, CD36, and CX3CR1 at the protein level. Pregnancy caused a shift toward higher frequencies of CD56bright cells in the blood caused by a numerical reduction in CD56dim cells. We demonstrate a role for chemokine receptor CX3CR1 in NK cell activation and define a subset of cytomegalovirus-induced decidual NK cells. Overall, this study provides key insights on NK cell immunity in pregnancy and reveals fundamental differences in the NK cell compartment during gestation. Taken together, this information will help improve treatments and immunotherapy strategies in pregnant individuals.

overall_design: Human natural killer cells were sorted from peripheral blood mononuclear cell samples from third-trimester pregnancies and non-pregnant individuals. Decidual NK cells were sorted from decidual single-cell suspension from term pregnancies.

first: Jennifer

last: Habel

first: Louise

middle: C

last: Rowntree

first: Katherine

last: Kedzierska


title: RNA sequencing of Metastatic urothelial carcinoma (UC)

city: Seattle

first: Sonali

last: Arora

state: WA

address: 1100 Fairview Ave N,

institute: FHCRC

summary: Histological variation is a common feature of metastatic cancer but its clonal origins and impact on disease history remains poorly defined. In this study, we developed a first-in-kind metastatic bladder cancer (BLCA) rapid autopsy cohort enriched in rare histological subtypes to extensively profile individuals with terminal disease. By reconstructing the evolutionary history of patient tumors, we determined that metastasis-to-metastasis seeding was the dominant driver of cancer spread and that increased polyclonal migration contributed to poor prognosis. The burden, heterogeneity, and timing of acquired genomic alterations were markedly different between histological subtypes. Plasmacytoid and neuroendocrine variants developed early genomic driver alterations that associated with shorter survival. Mutational signature analysis further revealed that plasmacytoid, but not other subtypes, utilized the Fanconi Anemia pathway to shield from chemotherapy-induced genomic scarring. Using experimental models, we demonstrated that Fanconi Anemia pathway activity positively correlated with resistance to cisplatin chemotherapy, demonstrating a molecular basis for therapy resistance in plasmacytoid patients. We report the first single-nucleus profiling of mBLCA histological subtypes, revealing mixed cell states in plasmacytoid tumors and that increased overall transcriptional heterogeneity was associated with longer patient survival. Characterization of the tumor microenvironment uncovered distinct patterns of immune activation across histological subtypes, with plasmacytoid tumors exhibiting an immune-inflamed profile, while squamous subtype was dominated by immunosuppressive interactions. Lastly, we demonstrated that post-mortem cell-free DNA captured both genomic heterogeneity and transcriptional activity of the subtypes, providing a potential strategy to non-invasively assess tumor identity and aggressiveness in patients with mBLCA. Our results provide new principles into how tumor heterogeneity shapes the evolutionary history of cancer progression within subtypes of human bladder cancer

overall_design: RNASeq of Metastatic Urothelial carcinoma samples

first: Hung-Ming

last: Lam

first: Gavin

last: Ha

first: Michael

last: Haffner

last: Hsieh

first: Rubin

last: Raychaudhuri


title: The PARP Inhibitor Talazoparib efficiently Suppresses Tumor Growth in Castration-Resistant Prostate Cancer

city: shang hai

first: Yi

last: Jiayan

address: pujian road

institute: SHANG HAI JIAO TONG UNIVERSITY

summary: To address the limited understanding of PARP inhibitor monotherapy in castration-resistant prostate cancer (CRPC), we investigated the antitumor effects of Talazoparib in CRPC cells with homologous recombination repair (HRR) gene mutations. We treated DU 145 and PC-3 cells with Talazoparib and observed reduced proliferation, migration, and colony formation. Western blot analysis showed increased apoptosis and DNA damage. RNA sequencing revealed downregulation of key HRR genes (BRCA1/2, ATM, ATR), and gene set enrichment analysis confirmed suppression of DNA repair pathways and activation of immune-related responses. These findings suggest that Talazoparib not only exploits synthetic lethality but also impairs HRR gene expression, supporting its potential as monotherapy in HRR-deficient CRPC.

overall_design: To evaluate the tumor-suppressive effects of Talazoparib in castration-resistant prostate cancer (CRPC), we selected DU 145 and PC-3 cell lines, representing HRR-deficient and HRR-proficient models, respectively. Cells were treated with increasing concentrations of Talazoparib (5 µM, 10 µM, and 20 µM) for 48 hours. Cell viability was assessed using CCK-8 assays, while colony formation and transwell assays were conducted to evaluate proliferation and migration. Western blot analysis was performed to detect apoptosis and DNA damage markers, including cleaved-PARP, cleaved-caspase-3, and γH2AX. Additionally, bulk RNA sequencing and Gene Set Enrichment Analysis (GSEA) were conducted to examine transcriptomic changes and pathway alterations under Talazoparib treatment.

first: Jiayan

last: Yi

first: Ang

first: Yibin

last: Zhou

first: Ruopeng

last: Su

first: Xinyu

first: Bo

first: Kai

last: Shen

last: Chai

first: Haotian

last: Wu

first: Wei

last: Xue

last: Wang

first: Yinjie

last: Zhu


title: parimifasor is a novel broad-spectrum anti-tumor drug

city: nanyang

last: Li

state: henan

address: No. 80, Changjiang Road

institute: Nanyang Institute of Technology

summary: Using transcriptome sequencing technology to confirm parimifasor as a potential antitumor drug.

overall_design: We identified parimifasor as a potential antitumor drug. In order to explore the mechanism of parimifasor, KYSE140 and LN229 cells were treated with 0.5 μM parimifasor or 0.2% DMSO (Control) for 36 hours, paired-end sequencing libraries were constructed with the ABclonal mRNA-seq Library Prep Kit (ABclonal, China) according to the manufacturer’s protocol. High-throughput sequencing was performed on an Illumina NovaSeq 6000 platform.


title: EFHD1 causes metabolic liver injury by triggering Ca2+-dependent mitochondrial fission

city: Salt Lake City

first: Dipayan

last: Chaudhuri

state: UT

institute: University of Utah

summary: The occurrence of metabolic liver disease is increasing globally. Multiple GWAS studies have found an association between elevated EFHD1 expression in the liver and markers for metabolic liver disease in diverse populations. EFHD1 is a calcium-sensing protein at the mitochondrial outer membrane and EFHD1 ablation has previously been shown to protect cardiac mitochondria. Here we utilize EFHD1 knockout (EFHD1-KO) models to assess whether EFHD1 represents a novel therapeutic target to treat metabolic liver disease. We found that EFHD1-KO mice exposed to diet-induced metabolic liver disease exhibited significant decreases in liver disease markers which correlated to lower levels of liver inflammation and fibrosis, when compared with control animals. This effect was also observed when EFHD1 was knocked down in the liver using a virus. On the cellular level, when comparing to wild-type cells, we found that EFHD1-KO cells exhibited significantly elongated mitochondria which were highly resistant to calcium-induced mitochondrial fission. Moreover, we observed significantly lower levels of mitochondrial dsRNA in diseased cells lacking EFHD1 which corresponded to lower expression levels of proteins associated with the integrated stress response (ISR). The ISR can be triggered by mitochondrial dsRNA release, resulting in hepatocyte damage in metabolic liver disease. These findings led us to hypothesize that EFHD1 ablation protects hepatocytes in metabolic liver disease by preventing excessive mitochondrial fissioning, lowering mitochondrial dsRNA release and reducing hepatocyte damage by the ISR. We therefore propose that EFHD1 represents a novel therapeutic pathway to treat metabolic liver disease.

overall_design: RNA collected from mouse livers treated with TriZOL. Mice were either WT BL6 mice or Efhd1-knockout (whole body) BL6 and were fed either a normal chow (experiment 18513) Gubra Amylin NASH (experiment 21222) diet.  Note that these were two separate experiments done months apart.

first: David

last: Eberhardt

first: Neeraj

last: Rai

first: Anthony

last: Balynas

first: Ashley

last: Bratt

first: William

middle: L

last: Holland

first: Scott

middle: A

last: Summers

first: Sihem

last: Boudina

first: Kimberley

middle: J

last: Evason

first: Vivek

last: Garg

first: Marcus

middle: G

last: Pezzolesi

first: Devorah

last: Stucki

first: Enrique

last: Balderas

first: Sandra

last: Lee

first: Patrice

middle: N

last: Mimche

first: Ryan

last: Bia

first: Sarah

last: Franklin

first: Yasmin

last: Masini

first: Robin

last: Shaw

first: Daisuke

last: Shimura

first: Emma

last: Rekate


title: Differential gene expression analysis in S-phase neurons derived from L1-GFP/5xFAD and L1-GFP mice

city: Kodaira

first: Fumio

last: Takahashi

address: 4-1-1 Ogawahigashi

country: Japan

institute: National Center of Neurology and Psychiatry

summary: Neurodegeneration involves entangled processes of neuronal autonomous and non-neuronal autonomous death, which leads to a collapse in the integrity of the neural network and causes behavioral symptoms. Here, we demonstrate that aberrant cell cycle reentry (CCR) is prominent in mature neurons and the replication fork in S-phase neurons acts as a target site for retrotransposition by long interspersed nuclear element-1 (L1) in neurodegeneration-prone 5xFAD mice. Interestingly, the morbid susceptibility of S-phase neurons to cell death has been attributed to enhanced L1 retrotransposition and DNA repair deficiency. Furthermore, deficit in sirtuin 6 expression and estrogen/prolactin signaling promote stochastic L1 retrotransposition and impair Brca1 expression in S-phase neurons, respectively. Importantly, L1 retrotransposition-related neuronal malfunction is correlated with conventional AD pathology. Current data suggest that the coincidence of enhanced L1 retrotransposition and DNA repair deficiency causes synthetic lethality in S-phase neurons, providing a previously unknown pathogenic mechanism of neurodegeneration.

overall_design: RNA-seq profiling of neurons in individual cell cycle phase with or without L1 retrotransposition derived from either L1-GFP/5xFAD and L1-GFP mice

first: Oki

last: Shinji

first: Yamamura

last: Takashi

first: Takahashi

last: Fumio


title: Implications of TEAD4 in Metabolic Processes of Gastric Cancer [Bisulfite-Seq]

city: Tehran

first: Massoud

last: Vosough

address: Bani Hashem Sq.

country: Iran

institute: Royan Institute

type: Methylation profiling by high throughput sequencing

summary: Gastric cancer (GC) is a prevalent malignancy worldwide, imposing a significant global health burden. Despite the development of various treatment strategies, effective management of GC remains elusive. Consequently, extensive research efforts have been directed towards uncovering the underlying molecular mechanisms of GC pathogenesis to develop novel and targeted therapeutic approaches. Among the identified signaling pathways, the Hippo pathway has emerged as a critical contributor to tumor development and acquired drug resistance in GC. It also interacts with multiple other pathways implicated in GC progression. Recent studies have highlighted the role of abnormal DNA methylation patterns in the early stages of GC development, rather than being confined to advanced stages. Specifically, the Hippo pathway member TEAD4 which is implicated in all four GC molecular subtypes, as classified by The Cancer Genome Atlas (TCGA) project, has been found to be hypomethylated in GC. In our research, we employed targeted hypermethylation using a combination of KRAB and DNMT3AL EpiEffectors to achieve epigenetic silencing of the TEAD4 promoter. Post-intervention, consistent with previous studies, we observed a reduction in the cancerous properties of the manipulated GC cells, such as proliferation, colony formation ability, migration, and invasion. Interestingly, transcriptomics results suggest that TEAD4 suppression may imply the downregulation of several carbohydrate-related metabolic pathways, DNA replication and repair mechanisms, as well as carbon metabolism. These findings may offer deeper insights into the multifaceted roles of TEAD4 in the progression of GC.

overall_design: Genomic DNA was extracted from from Tr.HGC-27-KRAB cells transfected with the DNMT3AL domain and the first set of gRNAs (i.e. 7gRNAs, designed to target TEAD4 gene promoter) on days 3, 7, and 14 post transfection, as well as in transfected HGC-27 cells with only 7gRNAs on days 3, 7, and 14 post-transfection, along with the untreated HGC-27 gastric cancer cells

first: Roya

last: Ramezankhani

first: Bernard K.

last: van der Veer

first: Amir

last: Amiri-Yekta

first: Salahadin

last: Bahrami

first: FatemehArefeh

last: Nami

first: Tine

last: Tricot

first: Afshin

last: Abdi Ghavidel

first: Yoke Chin

last: Chai

first: Catherine M.

last: Verfaillie


title: Mecp2 stabilizes the glucocorticoid system in active chromatin regions [scRNA-Seq]

city: Hangzhou

first: Xiaoping

last: Han

state: Zhejiang

address: Yuhangtang Road 866

department: Center for Stem Cell and Regenerative Medicine

institute: Zhejiang University School of Medicine

summary: Methyl-CpG-binding protein 2 (MECP2), a key epigenetic factor regulating gene expression via DNA/chromatin interactions, causes multisystem disorders when dysfunctional. However, its epigenetic regulatory mechanisms at the pan-tissue and multi-omics levels remain poorly understood. Here, we established comprehensive pan-tissue expression profiles in wild-type and Mecp2-knockout mice, revealing a crucial role for MECP2 in maintaining glucocorticoid (GC) signaling homeostasis. Single-cell epigenomic analyses demonstrated widespread increases in chromatin accessibility at GC-induced genes (GIGs) upon Mecp2 deficiency. Through innovative single-cell multi-omics profiling of the nervous system, we further revealed that GIG dysregulation primarily disrupts neural homeostasis via non-neuronal cells. Mechanistically, we identified a dual regulatory mode of MECP2: (1) competitively inhibiting NR3C1 binding to the cis-regulatory elements of GIGs in active chromatin regions, and (2) specifically disrupting NR3C1-NCOA1 coactivator interactions. These findings not only elucidate a novel MECP2-NR3C1-NCOA1 axis in GC system regulation but also suggest potential therapeutic targets for Rett syndrome.

overall_design: scRNA-seq data of six regions (brain stem, cerebellum, diencephalon, pituitary, spinal cord, and telencephalon) from WT and Mecp2 KO mice were obtained. Each condition contained three biological replicates.

first: Daiyuan

last: Liu

first: Jianhui

last: Chen

first: Xueyi

last: Wang

first: Guoji

last: Guo


city: changsha

first: Huilin

middle: huilin

last: Yang

state: huannan

address: Donghu Street

institute: Hunan Agricultural University

summary: Currently, research on the impact of fertilizers on natural enemies, particularly spiders, is extremely limited. Most existing studies focus on field population dynamics and community structure, with scarce reporting on underlying mechanisms. This project, titled "Study on the Effects and Mechanisms of Urea on Predation Behavior of Farmland Spiders," integrates multidisciplinary theories and employs a combined approach of field investigations and laboratory experiments. It aims to Reveal the predatory strategies of dominant spider populations under chronic urea stress in agricultural ecosystems; to analyze the effects and mechanisms of chronic urea stress on predation-related metabolic, detoxification, and neuromodulation functions in dominant spider species from biological, physiological, cytomorphological, and multi-omics perspectives; to elucidate the comprehensive regulatory role and mechanisms of spider gut microbiota in mediating predation function responses to urea stress.Collectively, this research will clarify the impact and mechanisms of urea on the predation function of farmland spiders, providing a theoretical foundation and practical support for optimizing urea application in agricultural production and achieving the optimal comprehensive effects on spider predation services.

overall_design: This study employs an integrated approach to investigate the impact of urea stress on Pardosa pseudoannulata, commencing with field collection of adult spiders (n=300) from rice agroecosystems followed by laboratory acclimation under controlled conditions (25±1°C, 70% RH, 12L:12D photoperiod). Spiders were exposed to urea-amended soil at environmentally relevant concentrations (0, 200, and 400 mg/kg) for 30 days to encompass molting cycles. The experimental framework systematically evaluates: (1) urea-induced alterations in predatory behavior through quantitative video tracking of attack latency, prey consumption rate, and handling time using Drosophila melanogaster as prey; (2) physiological responses via biochemical assays measuring energy substrates (soluble sugars, glycogen) and enzyme activities (CYP450, GST, LDH, ACP); (3) structural changes in gut microbiota through 16S rRNA sequencing (V3-V4 region) with subsequent α/β-diversity and functional prediction analyses; and (4) gut metabolic profile shifts using LC-MS/MS-based metabolomics with HILIC-UPLC separation. Statistical validation incorporates ANOVA with Tukey's HSD for behavioral/enzymatic data, PERMANOVA for multivariate omics datasets, and Spearman correlation to establish microbiota-metabolite-phenotype linkages, collectively enabling a mechanistic understanding of urea's ecotoxicological effects on this key predatory arthropod.

first: Yang

last: Huilin

first: Huang

last: Siqi


title: Gene expression of Uropathogenic Escherichia coli (UPEC) from different clinical categories of complicated urinary tract infection and Escherichia coli from asymptomatic bacteriuria

city: Subang Jaya

first: Vinod

last: Pallath

address: Jalan Lagoon Selatan, Bandar Sunway,

department: Jeffrey Cheah School of Medicine and Health Sciences.

country: Malaysia

institute: Monash University Malaysia

summary: Escherichia coli is the predominant agent causing both different disease categories of complicated urinary tract infections (UTIs) and asymptomatic bacteriuria (ASB) cases. This study employed microarray analysis to identify the differences and similarities in the expression of genes among the Uropathogenic Escherichia coli (UPEC)  and two ASB E.coli isolates that represent different end continuums of its disease severities.

overall_design:
Six UPEC isolates from different complicated urinary tract infection (cUTI) categories  (cystitis (EC259), pyelonephritis (EC225), urosepsis (EC285), recurrent UTI (EC240), catheter urinary tract infection (EC299) and UPEC with co-morbidities (EC287) were isolated from urine samples of UTI-confirmed patients were treated as test samples. As for the control, two ASB E. coli strains, one ASB E. coli HPP (EC095) (identified as possessed with a higher number of UPEC-associated virulence genes through polymerase chain reaction (PCR))  and one  ASB E. coli LPP (EC114) (identified to lack all UPEC-associated virulence genes through PCR) were isolated from urine samples of pregnant women. All UPECs and ASB E.coli were grown until the mid-log phase.  All the strains were treated as biological replicates.

Grant ID: FRGS/1/2018/SKK08/UM/02/1 (FP026-2018A)
Grant Title: Fundamental Research Grant Scheme (FRGS)
Grantee: Vinod Pallath
Funding Source: Ministry of Higher Education (MOHE), Malaysia

first: Kumuthamalar

last: Vellasamy

first: Lalitha

last: Maniam


title: miR-29a-3p affects DNA methylation level in fetal mouse liver

city: Nanjing

first: Huichen

last: Song

state: Jiangsu

address: Qixia District, Xianlin Road No.163

institute: Nanjing university

summary: Obesity during pregnancy is linked to a high risk of offspring overweight, insulin resistance, type 2 diabetes, and cardiometabolic disease in later life. However, the underlying mechanisms by which maternal factors drive these long-lasting effects remain to be fully elucidated. In our study, we have demonstrated that in diet-induced-obesity (DIO) pregnant mice, maternal small extracellular vesicles (sEV) in circulating system have the ability to cross the placental barrier and reach the liver of fetal mice, exerting a sustained adverse impact on offspring insulin sensitivity. Further investigations have revealed that pathogenically increased miR-29a-3p in maternal sEV from DIO mice can be delivered into livers of fetal offspring. Elevated miR-29a-3p subsequently alter epigenetic state in fetal liver via targeting several key methyltransferases and demethylases, interrupting the DNA methylation landscape, including hypomethylation of PGC-1α. Such epigenetic remodeling abnormally promotes early hepatic gluconeogenesis at fetal stage that contribute to the adult metabolic disturbance in offspring. Taken together, our finding suggests that the transplacental delivery of maternal sEV could serve as a potential mechanism for prenatal programming of metabolic health in offspring.

overall_design: Pregnant mice with normal diet were divided into two groups, one group was injected with extracellular vesicles rich in miR-29a-3p, and the control group was injected with extracellular vesicles rich in NC, once a day from day 12.5 of gestation for a total of 6 times. DNA methylation level in fetal liver was detected


title: Diet-induced obesity affects miRNA expression in plasma extracellular vesicles of pregnant mice

overall_design: Female mice were divided into two groups, the experimental group was fed with high-fat diet, and the control group was fed with normal diet. After 8 weeks, male mice on a normal diet will be mated, and miRNA expression levels in plasma extracellular vesicles of pregnant mice will be measured


title: Implications of TEAD4 in Metabolic Processes of Gastric Cancer [RNA-Seq]

first: Massoud

last: Vosough

overall_design: RNA samples were collected from Tr.HGC-27-KRAB cells transfected with the DNMT3AL domain and two sets of gRNAs (designed to target two regions in TEAD4 gene promoter), as well as in transfected cells with only gRNAs on day 3 post-transfection, and Tr.HGC-27-KRAB cells transfected with the DNMT3AL domain and the first set of gRNAs (i.e. 7gRNAs) on day 14 post-transfection ,along with the untreated HGC-27 gastric cancer cells

first: Roya

last: Ramezankhani

first: Bernard K.

last: van der Veer

first: Amir

last: Amiri-Yekta

first: Salahadin

last: Bahrami

first: FatemehArefeh

last: Nami


title: Comparative single-cell analysis of multiple models of retinitis pigmentosa reveals common pro-survival mechanisms activated in photoreceptors

city: Pozzuoli

first: Santiago

last: Negueruela

address: Via Campi Flegrei, 34

department: Genetic Medicie

institute: Telethon Institute of Genetics and Medicine (TIGEM)

summary: Retinitis pigmentosa (RP) is a group of inherited retinal diseases marked by the progressive degeneration of photoreceptors, ultimately leading to severe vision loss or blindness. The vast genetic heterogeneity of RP results in highly variable disease phenotypes, yet the identification of shared, mutation-independent mechanisms could provide a foundation for broadly applicable therapeutic strategies. To explore such mechanisms, we generated scRNA-seq datasets across three key timepoints in two RP mouse models, rd10 and P347S, and integrated them with public datasets from rd1 and AdipoR1-KO models. Time-course differential expression and gene regulatory network analyses revealed a conserved transcriptional response to retinal degeneration across photoreceptor types and disease models. Transcription factors such as Cebpd, Stat3, and E2f6 emerged as central regulators, consistently upregulated and potentially mediating pro-survival mechanisms. IEGs like Junb, Fosb, and Egr1 were consistently activated, configuring an early response to stress associated to apoptotic responses. Furthermore, we identified epigenetic regulators such as Dnmt1 and Atf7 upregulated across models, pointing to a role for chromatin remodeling in retinal degeneration. These findings support the existence of a core stress-induced regulatory program in RP and highlight promising targets for the development of mutation-independent, disease-modifying therapies.

overall_design: Retinas from WT (P10, P18, P30, P60), Pde6brd10 (P10, P18, P30)  and RHO-P347S+/+ mice (P10, P30 , P60) were collected, dissociated and sequenced by scRNAseq

first: Sandro

last: Banfi


title: Diet-induced obesity affects miRNA expression in plasma extracellular vesicles of pregnant women

type: Non-coding RNA profiling by high throughput sequencing

overall_design: According to the pre-pregnancy BMI index, the pregnant women were divided into two groups, the obese group with BMI>28, and the normal group with BMI<24. The miRNA of plasma extracellular vesicles in the two groups were detected in the third trimester


title: Diet-induced obesity affects miRNAs expression in fetal mouse liver

overall_design: Female mouse were divided into two groups, the experimental group was fed with high-fat diet, and the control group was fed with normal diet. After 8 weeks, the males were mated with the normal diet, and the expression level of miRNA in fetal liver was detected on gestational day 18.5


title: Transcriptional changes and epigenetic landscapes in fetal hematopoietic stem and progenitor cells with DDX21 knockout

city: Shatin

first: Hoi-Hung

middle: Hoi Hung

last: Cheung

state: NT

address: Rm.707, School of Biomedical Sciences, Area 39, The Chinese University of Hong Kong

department: School of Biomedical Sciences

country: Hong Kong

institute: The Chinese University of Hong Kong

summary: Fetal hematopoietic stem cells and their committed progenitors (HSPCs) are highly proliferative cells that rely on active ribosome biogenesis to support their rapid expansion during fetal hematopoiesis. Insufficient ribosome biogenesis, a pathological condition known as ribosomopathy, activates the p53 pathway and induces cell cycle arrest in immature progenitor cells, leading to disrupted hematopoiesis and erythroid aplasia (anemia). DDX21 is an RNA helicase that regulates ribosome biogenesis by modulating rRNA splicing, processing, and ribosomal protein transcription. To elucidate the role of DDX21 in hematopoiesis, we generated Ddx21 conditional knockout (Ddx21cKO) in hematopoietic cells by crossing Ddx21f/f with Vav1-Cre mice. The Ddx21cKO embryos showed defective hematopoiesis and decreased HSPC numbers and their committed progenitors (CMP, GMP, and MEP). In this study, transcriptional changes in E13.5 HSPCs were analyzed by RNA-seq. Epigenetic marks associated active chromatin (H3K4me3, H3K27ac) and repressive chromatin (H3K27me3, H4K4me1) were analyzed by CUT&Tag. Chromatin accessibility was analyzed by ATAC-seq, whereas chromatin occupancies by Ddx21 and Kdm5a were analyzed by CUT&Tag.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq transcriptomic profiling of FACS-sorted E13.5 fetal liver LK (lineage- Kit+) cells from WT (Ddx21f/f) and Ddx21-cKO (Vav1-Cre; Ddx21f/f) embryos.

first: Adrian On-Wah

last: Leung

first: Chang

last: Li

first: Albert


title: Host eicosanoid signals define a granuloma-associated fibroblast population coordinating mycobacterial containment

city: Durham

first: David

last: Tobin

state: NC

address: 207 Research Drive

institute: Duke University

summary: We used single-cell RNA sequencing to interrogate granulomas from Mycobacterium marinum infected zebrafish (Danio rerio) of a genetic mutant. This sample was compared to a previously published granuloma scRNAseq dataset from wildtype zebrafish. Granulomas are comprised of several cell types and we sought to understand the consequences of genetic disruption of the gene leukotriene A4 hydrolase (lta4h) on granuloma cells types and cell-specific transcription. This is the first comparison of mycobacterial granuloma scRNAseq from a genetic mutant to wildtype.

overall_design: Granulomas were dissected from infected zebrafish adults. Single-cell suspensions were generated by brief digestion with trypsin and sent for 10X Genomics scRNAseq processing.

first: Erika

last: Hughes

first: Simon

last: Gregory


title: TJ0113 alleviates ferroptosis by improving mitochondria of renal tubules in the transition from AKI to CKD

first: Yifei

last: Sun

address: West Wenyi Road, 1369

institute: Liangzhu Laboratory

summary: Acute kidney injury (AKI) is a prevalent clinical complication with a high risk of progression to chronic kidney disease (CKD), yet effective drugs to prevent or treat the transition from AKI to CKD are still lacking. The kidney is an organ rich in mitochondria and mitochondrial dysfunction plays a pivotal role in the progression from AKI to CKD. In this study, we established a mouse model of bilateral renal artery ischemia-reperfusion injury to investigate whether TJ0113, a mitophagy inducer currently in Phase 2 of clinical trials (NCT06596005), can be used to mitigate the transition from AKI to CKD. We found that TJ0113 improved the high mortality rate and renal dysfunction in AKI mice, alleviated renal injury, inflammation, and interstitial fibrosis during the transition from AKI to CKD, and improved mitochondrial quality in renal tubules. RNA-seq results showed that TJ0113 reduced the expression of activating transcription factor 3 (ATF3), which is upstream of the classic ferroptosis pathway. In summary, our data show that TJ0113 maintains mitochondrial quality in renal tubules through mitophagy, thereby improving the progression from AKI to CKD, and represents a potential drug for preventing and treating the transition from AKI to CKD.

overall_design: RNA-seq profiling of mouse kidneys on 14th day post-bilateral ischemic-reperfusion injury   (bIRI) surgery with TJ0113 or Vehicle treatment.

first: Xiaoyan

last: Xu


title: Gene expression profile from single cell level of retinal cells from optic cup of injected Abca4KO mice with miR-181a/b sponge therapeutic

summary: We observed a beneficial effect on Abca4KO mice phenotype upon miR-181a/b sponge treatment. Then, we decided to perform single cell analysis to better understand the pathway associated with amelioration observed.

overall_design: Abca4KO mice were injected with miR-181a/b sponge in one eye and with a control vector in the controlateral. Subretinal injection were performed at 2 months of age and samples collected and analyzed at 4 months post-treatment.

first: Simona

last: Brillante

first: Alessia

last: Indrieri


title: Gene expression profile at single cell level of immune cells from the deep cervical lymph nodes (dCLNs), superficial cervical lymph nodes (sCLNs), and inguinal lymph nodes (iLNs) of wild-type and Alzheimer's disease transgenic animals (5xFAD)vdjb

city: Rehovot

first: Michal

last: Schwartz

address: Herzl 234

country: Israel

institute: Weizmann Institute of Science

summary: The dCLNs are lymph nodes specialized in draining cerebrospinal fluid (CSF). We used single cell RNA sequencing (scRNA-seq) to characterize the immune cell populations in the dCLNs compared to other draining lymph nodes. We compared the immune landscape of the dCLNs between healthy WT mice and 5xFAD mice to investigate the role of dCLNs immunity in AD progression. Additionaly, we sequenced the TCR and BCR transcripts to analyze the clonal distribution of T-cells and B-cells in each lymph node.

overall_design: Cells were isolated from the dCLNs, sCLNs, and iLNs of 10-11-month-old WT and 5xFAD mice. Cells were hashed using anti-mouse Totalseq-C 001,002,003 or 004  hashtags. Gene expression (GEX), V(D)J (TCR and BCR) and Cell Surface Protein library from the same samples were then constructed using the Chromium Next GEM Single Cell 5' Reagent Kit v2 (Dual Index) with Feature Barcode technology for Cell Surface Protein and Immune Receptor Mapping.

first: Castellani

last: Giulia


title: Gene expression profile at single cell level of immune cells from the deep cervical lymph nodes (dCLNs), superficial cervical lymph nodes (sCLNs), and inguinal lymph nodes (iLNs) of wild-type (WT) and Alzheimer's disease (AD) transgenic animals (5xFAD)GEX


title: Gene expression profile at single cell level of immune cells from the deep cervical lymph nodes (dCLNs), superficial cervical lymph nodes (sCLNs), and inguinal lymph nodes (iLNs) of wild-type and Alzheimer's disease (AD) transgenic animals (5xFAD)vdj_t


title: Comparative single-cell transcriptional profiling reveals regional diversity of cell types in the human adult cerebral cortex

city: Beijing

first: xiaoqun

last: wang

state: Beijing

address: 15 Datun Road, Chaoyang District

department: Institute of Biophysics

institute: Chinese Academy of Sciences

summary: In summary, our research has  illustrated the cellular complexity and molecular support in specialized cortex regions, contributing to understanding cortex function and providing a resource for future studies.

overall_design: We sampled and performed snRNA-seq on human adult cerebral cortex  tissues  from five different regions with biological replicates

first: Xiaoqun

last: Wang

first: Bo

last: Zeng

first: Qiang

last: Ma

first: Meng

last: Yang


title: Gene expression profile at single cell level of immune cells from the deep cervical lymph nodes (dCLNs), superficial cervical lymph nodes (sCLNs), and inguinal lymph nodes (iLNs) of wild-type (WT) and Alzheimer's disease (AD) transgenic animals (5xFAD)

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

overall_design: Refer to individual Series


title: Nup153 regulates neuronal responsiveness through HDAC1-mediated epigenetic modulation [RNA-seq]

city: Dresden

first: Abhinav

last: Soni

state: Saxony

address: Tatzberg 41

department: Nuclear architecture in neural plasticity and aging

country: Germany

institute: German Center for Neurodegenerative Diseases, Dresden

summary: Neural activity-dependent gene regulation is central to the development of neural networks and neuronal plasticity. Induction of activity-dependent gene programs is equally important as repression of these programs, and both need to be balanced carefully. However, little is known about how repressive mechanisms modulate neuronal responsiveness across the genome before stimulation. Here, we identify nucleoporin-dependent regulation of neuronal responsiveness in which Nup153 represses neuronal genes including activity-regulated genes (ARGs) in the basal state. By characterizing the genome-wide landscape of chromatin accessibility, histone modifications and Nup153 chromatin binding, we show that Nup153 directly influences their target genes and associated chromatin states through both basal activity-dependent and -independent mechanisms. Mechanistically, Nup153 recruits HDAC1 to regulate histone acetylation and repress target chromatin regions. We propose that Nup153 acts as a structural platform to recruit epigenetic repressor to maintain activity-dependent programs in the poised state, thus maintaining neuronal responsiveness as a gatekeeper.

overall_design: To investigate the extent to which Nup153 regulates genetic programs on a genome-wide scale in mature neurons, we performed RNA-seq analyses after Nup153 knockdown. Nup153 knockdown was performed using  shNup153-1/shNup153-2 and shControl was used as a control shRNA. Total RNA was collected either from basal state primary cortical neurons (PCNs) at DIV 13 after five days of AAV infection or TTX-AP5 treated pre-silenced neurons.

first: Nicole

last: Rund

first: Mathias

last: Lesche

first: Katrin

last: Sameith

first: Andreas

last: Dahl

first: Tomohisa

last: Toda


title: Comparative Analysis of Yukmijihwang-tang and Palmijihwang-tang: Lifespan Extension and Kidney Function Improvement in Aging Models

city: Daejeon

first: You Mee

last: Ahn

address: Yuseong-daero, Yuseong-gu

institute: KOREA INSTITUTE OF ORIENTAL MEDICINE

summary: This study aims to investigate the lifespan extension effects of YM and PM, compare their influence on kidney aging markers and aging-related gene expression in aged mice, and identify their action pathways from a hormonal perspective.

overall_design:
Male C57BL/6 mice, after a 5-month acclimatization period, mice were divided into three groups: OLD, the natural aging group; YM, which received 100 mg/kg/day of YM orally 5 days a week; and PM, which received the same dosage and schedule for PM. Additionally, a group of young mice (Y) was included as a control group. YM and PM administration began when the mice were nineteen months of age and continued until they were 24 months old. Furthermore, three-month-old C57BL/6 mice were obtained to serve as young controls for comparison with the older groups.
Comparative gene expression profiling analysis of kidney RNA-seq data obtained from C57BL/6 mice in OLD, the natural aging group; YM, 100 mg/kg/day of YM orally 5 days a week; PM, 100 mg/kg/day of YM orally 5 days a week.

first: Geonhui

last: Kang

first: Jeeyoun

last: Jung

first: So Min

last: Lee

first: Seulgi

first: Dong Seok

last: Cha


title: Alveolar epithelial depletion of βPIX drives progressive pulmonary fibrosis in mice: therapeutic implications in human pulmonary fibrosis

first: Woogil

last: Song

address: KAIST, Daejeon 34141, Korea

department: Graduate School of Medical science and engineering

institute: KAIST

summary: We identifies βPIX as a crucial regulator of lung fibrosis and establishes an IPF-like animal model for gaining mechanistic insights into potential therapeutic strategies.

overall_design: This study design involves deleting the βPIX gene specifically in alveolar type 2 (AT2) cells in mice to induce progressive lung fibrosis and exploring the role of βPIX in lung fibrosis by examining cellular senescence, collagen accumulation, and the effects of Wnt/β-catenin signaling restoration.

first: Han-Byeol

last: Kim

first: Jeong

middle: S

first: Eun-Young

last: Shin

first: Eung-Gook


title: Characteriration of mitochondrial stress response in Luhmes-derived dopaminergic neurons; Comparative expression profile using RNAseq after 8 hours of Antimycin + Oligomycin treatment in differentiated Luhmes cells

city: Paris

first: Philippe

last: Ravassard

address: ICM 47 bd de l'hopital

institute: Paris Brain Institute

summary: Responsiveness of 6 days old differentiated Luhmes cells to mitochondrial stress induced by 8 hours treatment with Antimycin-A and Oligomycin analyzed by RNA-seq. The Unfolded Protein Response of the Endoplasmic Reticulum is induced upon stress in human dopaminergic neurons, and modulates mitochondrial homeostasis and transcriptional programs including expression of long non-coding RNAs (lncRNAs).

overall_design: 4 independent batches of differentaited Luhmes cells were treated for 8 hours with a combination of Antimycin A (25µM) and Oligomycin (10µM) and compared to 4 independent batches of differentaited Luhmes cells  treated with vehicle (DMSO). For each batches 4 technical replicates were used.

first: Jana

last: Heneine

first: Hélène

last: Cheval


title: The mechanism of cardiotoxicity induced by piperlopicin and bufalin was revealed by epitranscriptomics

city: Fuzhou

first: Yiyang

last: Chen

address: No. 1 Xueyuan Road, Shangjie Town, Minhou County, Fuzhou City, Fujian Province

institute: Fujian Medical University

summary: By using epitranscriptomics, the mechanism of cardiotoxicity induced by piperlopicin and bufalin was discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that piperlopicin and bufalin altered m6A levels within the cells.

overall_design: To investigate whether m6A modification is involved in cardiotoxicity following piperlopicin and bufalin treatment, we performed MeRIP-seq on control cells and cells treated with piperlopicin and bufalin.

first: Xinyue

last: Gao

first: Jian

last: Zhang

first: Yifan

last: Lin


title: Transcriptional profiling of microglia versus brain engrafted monocyte-derived macrophages

city: St. Louis

first: Jonathan

last: Kipnis

state: MO

address: 4515 McKinley Ave

institute: Washington University in St. Louis

summary: Mouse microglia are thought to originate exclusively from primitive macrophage progenitors in the yolk sac (YS) and to persist throughout life without much contribution from definitive hematopoiesis. Here, using lineage tracing, pharmacological manipulation, and RNA-sequencing, we elucidated the presence and characteristics of monocyte-derived macrophages (MDMs) in the brain parenchyma at baseline and during microglia repopulation, and defined the core transcriptional signatures of brain-engrafted MDMs. Lineage tracing mouse models revealed that MDMs transiently express CD206 during brain engraftment as microglial precursors. We found that brain-engrafted MDMs exhibit transcriptional and epigenetic characteristics akin to meningeal macrophages, likely due to environmental imprinting within the meningeal space. Utilizing parabiosis and skull transplantation, we demonstrated that monocytes from both peripheral blood and skull bone marrow can repopulate microglia-depleted brains. Our results reveal the heterogeneous origins and functional dynamics of brain parenchymal macrophages at baseline and in models of microglia depletion.

overall_design: To dissect the transcriptional differences between brain-engrafted MDMs and YS-derived microglia, we isolated tdTomato+ MDMs and tdTomato- YS-derived microglia from Ms4a3Cre:R26-tdTomato mice after PLX-3x treatment, followed by one month of repopulation.

first: Siling

last: Du


title: An integrated single cell and spatial transcriptomic map of Tumor Margin in Colorectal Cancer

city: shanghai

first: Dengfeng

last: Huang

address: 301 Yanchang Middle Road

institute: Shanghai Tenth People's Hospital

summary: Solid tumors are highly heterogeneous complex ecosystems. By dissecting the tumor ecosystem, particularly around the tumor periphery, we can gain deeper insights into the mechanisms of tumor cell infiltration and invasion.

overall_design:
Single-cell  RNA sequencing of adjacent normal tissues (n=8) and adjacent tumor tissues (n=8) from the same CRC cancer patient

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Due to patient privacy protection measures, we are unable to provide raw data at this time
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first: Dexi

last: Bi

first: Feifei


title: Multimodal perspectives on the upper layer neurogenesis in the murine cerebral cortex

first: Tabitha

last: Rücker

address: 25, rue du Docteur Roux

institute: Institut Pasteur

summary: Upper layer corticogenesis provides mammals with a range of additional cognitive circuits. Through indirect neurogenesis, neuronal progenitor cells transition from radial glia cells to an intermediate stage, where they exponentially increase neuronal output, migrate into the upper regions of the neocortex, and settle as excitatory projection neurons. During this process, Glast1+ (Glutamate aspartate transporter 1) progenitor cells exit the cell cycle, begin to express NeuroD1 (Neuronal Differentiation 1), and irreversibly commit to a neuronal fate. The regulatory landscape governing the specific formation of the upper layers is not fully understood. In particular, the molecular mechanisms underlying the gradual transition of neurons into the post-mitotic state remain unresolved. A central question in this process is the influence of prenatal stressors on upper layer corticogenesis. In this study, we created a multimodal map of neurogenesis under both untreated and immune-activated conditions in a mouse model. Thereby, we monitored subtle canonical Wnt pathway-associated patterns that could explain the spontaneous aetiology of autism spectrum disorders or late-onset neurodegenerative diseases.

overall_design:
Developing murine brains were isolated at daily intervals during prenatal and postnatal stages, from 14 days after mating to 7 days after birth. Brain samples were dissociated and subjected to fluorescence-activated cell sorting to distinguish between cells with constitutive expression of a fluorophore driven by the CAG promoter and 'pure' neuronal cells at the peak of neurogenesis, indicated by the presence of a fluorescent dye driven by the Glast1 or NeuroD1 promoters, respectively.
To study the effects of maternal immune activation (MIA), pregnant mice were challenged by two injections of PolyI:C (mimicking viral immune activation) during acute neurogenesis.

first: Birgit

last: Schwanke

first: Kerstin

last: Reumann

first: Patrick

last: Blümke

first: Jacqueline

last: Nakel

first: Daniela

last: Indenbirken

first: Thomas

last: Günther

first: Sabine

last: Hoffmeister-Ullerich

first: Stephanie

last: Stanelle-Bertram

first: Gülsah

last: Gabriel

first: Adam

last: Grundhoff

first: Froylan

last: Calderon de Anda


title: Genome-wide EDS1-dependent H3K9 acetylation patterns in Topless-related 1 (TPR1) overexpressing Arabidopsis plants

city: Cologne

last: Griebel

address: Carl-von-Linne-Weg 10

department: Department of Plant Microbe Interactions

institute: Max-Planck Institute for Plant Breeding Research

summary: We present here genome-wide H3K9 acetylation data in Arabidopsis thaliana plants overexpressing TPR1 (Topless-related 1) -GFP driven by its native promoter (TPR1-OX). We compared the H3K9 acetylation of the TPR1-OX auto-immune plants in WT (Col-0) background with eds1-2 mutant background plants which do not show the auto-immune phenotype.

overall_design: ChIP and library preparation was done using 2 g leaf material of TPR1-GFP and TPR1-GFP eds1-2 as described (Latrasse et al., 2017) by using Anti-acetyl-Histone H3 Lys 9 antibody (07-352, Millipore). Leaf material of 6-week-old plants was used and two biological replicates were performed and analyzed

first: Moussa

last: Benhamed

first: Lorenzo

last: Concia

first: Dmitry

last: Lapin

first: Jane

middle: E

last: Parker


title: The role of glutaminolysis and mitochondrial pyruvate import on plasma cell differentiation

status: Public on Jul 30 2026

city: Atlanta

first: Chris

last: Scharer

state: GA

address: 1510 Clifton Rd, Suite 3086A

department: Microbiology and Immunology

institute: Emory University

summary: The efficiencies with which activated B lymphocytes proliferate and develop into antibody (Ab)-secreting plasma cells are critical determinants of adaptive humoral immunity and central to sustaining certain autoimmune diseases. Increasing evidence indicates that specific pathways in intermediary metabolism, or their substrate supply, influence lymphocyte differentiation and function. To investigate the role of glutaminolysis and mitochondrial pyruvate import on plasma cell differentiation flow-purified germinal center B cells were stimulated in the presence of control or CB-839 to inhibit GLS1 and UK-5099 to inhibit mitochondiral pyruvate import.  Using RNA-seq, the transcriptional consequnces of metabolic manipulation were quantitated.

overall_design: RNA-seq profiling of germinal center B cells in triplicate treated with control, UK-5099, or CD-839.

first: Christopher

middle: D

first: Mark

last: Boothby


title: Nup153 regulates neuronal responsiveness through HDAC1-mediated epigenetic modulation [DamID-seq]

first: Abhinav

last: Soni

overall_design: To investigate direct function of Nup153 on chromatin organization, we employed Targeted DamID (TaDa PMID: 35468895) in primary cortical neurons (PCNs). Lentivirus particles carrying DAM control or DAM-Nup153 were applied at DIV 8, and samples were collected at DIV13.

first: Tomohisa

last: Toda

first: Stavroual

last: Petridi

first: Jelle

last: van den Ameele


title: GPX3 suppresses lung adenocarcinoma progression through HSPB1 ubiquitination and Hippo pathway activation

first: Yiquan

last: Xu

address: Fujian Cancer Hospital

institute: Fujian meidical university

summary: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer; however, its prognosis remains poor, and the underlying molecular mechanisms have yet to be fully elucidated. In this study, a prognostic model was constructed based on manganese metabolism-related genes, which effectively stratifies LUAD patients with different prognoses and drug sensitivity. Mendelian randomization analysis identified glutathione peroxidase 3 (GPX3) as a key prognostic gene, which was downregulated in LUAD and significantly correlated with favorable outcomes.

overall_design: Functionally, GPX3 was found to inhibit LUAD cell proliferation, invasion, and metastasis while promoting apoptosis. Mechanistically, GPX3 binds to heat shock protein β-1 (HSPB1), induces its ubiquitination, and facilitates its degradation, thereby activating the Hippo signaling pathway and suppressing malignant phenotypes in LUAD cells. In summary, this study not only established a robust prognostic model based on manganese metabolism-related genes but also uncovered the critical regulatory role of the GPX3/HSPB1/YAP axis in LUAD progression, underscoring the therapeutic potential of targeting GPX3.

first: Sixuan

last: Wu


title: The effect of sEV/miR-29a-3p on glucose metabolism in fetal rat liver

first: Huichen

last: Song

address: Qixia District, Xianlin Road No.163

institute: Nanjing university

summary: Obesity during pregnancy is linked to a high risk of offspring overweight, insulin resistance, type 2 diabetes, and cardiometabolic disease in later life. However, the underlying mechanisms by which maternal factors drive these long-lasting effects remain to be fully elucidated. In our study, we have demonstrated that in diet-induced-obesity (DIO) pregnant mice, maternal small extracellular vesicles (sEV) in circulating system have the ability to cross the placental barrier and reach the liver of fetal mice, exerting a sustained adverse impact on offspring insulin sensitivity. Further investigations have revealed that pathogenically increased miR-29a-3p in maternal sEV from DIO mice can be delivered into livers of fetal offspring. Elevated miR-29a-3p subsequently alter epigenetic state in fetal liver via targeting several key methyltransferases and demethylases, interrupting the DNA methylation landscape, including hypomethylation of PGC-1α. Such epigenetic remodeling abnormally promotes early hepatic gluconeogenesis at fetal stage that contribute to the adult metabolic disturbance in offspring. Taken together, our finding suggests that the transplacental delivery of maternal sEV could serve as a potential mechanism for prenatal programming of metabolic health in offspring.

overall_design: Pregnant mice with normal diet were divided into two groups, the experimental group was injected with extracellular vesicles rich in miR-29a-3p, and the control group was injected with extracellular vesicles rich in NC, once a day for 6 times from day 12.5 of gestation. The fetal liver tissues of the experimental group and the control group were collected for transcriptome sequencing


title: A Multi-Omics Network Identifies Neutrophil Elastase-Positive Extracellular Vesicles in Plasma of Alpha-1 Antitrypsin Deficient Individuals as Accelerants of Lung Inflammation

city: Gainesville

first: Nazli

last: Khodayari

state: FL

department: Pulmonary Medicine

institute: University of Florida

summary: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder caused by mutations in SERPINA1, leading to chronic obstructive pulmonary disease (COPD) and liver disease. Neutrophils are key regulators of inflammatory signaling networks, however, their dysregulation in AATD and associated molecular mechanism are not well understood yet. Herein, we employed a multi-omics approach, integrating RNA sequencing (RNA-seq) and metabolomics, to comprehensively characterize neutrophil dysfunction in AATD. RNA-seq analysis of blood neutrophils from AATD individuals revealed transcriptional dysregulation in the genes highly involved in intracellular signaling cassette, immune response-activating and regulating signaling pathways, and regulation of signal transductions which govern inflammation and metabolic adaptation. Isolation and characterization of neutrophil-derived extracellular vesicles (EV) further demonstrated an increased plasma burden of neutrophil elastase (NE)-rich EV with elevated surface-bound NE. Metabolomic profiling revealed that these EV are enriched with pro-inflammatory metabolites linked to dysregulated signaling pathways. Integrated transcriptomic and metabolomic network analysis revealed that dysregulated neutrophil gene expression and signaling pathways reshape EV metabolic cargo, linking metabolic reprogramming to inflammatory signal transduction in AATD. Moreover, differentially expressed EV metabolites may modulate gene expression in EV recipient cells, further sustaining chronic inflammation in AATD. These findings establish a mechanistic link between neutrophil gene dysregulation and EV-driven inflammatory signaling, revealing how metabolic reprogramming of EV cargo influences cellular crosstalk via cytokine and protease-mediated pathways. The observed upregulation of interferon,  pattern recognition receptors, and cytokine-mediated signaling pathways in neutrophils suggests a potential feedback loop amplifying inflammation in AATD and COPD.

overall_design: To describe the neuotrophil elastase positive extracellular vesicle mechanism in AATD, we performed RNA-seq on isolated neutrophils from two cohorts (AATD and Healthy).

first: Zachary

middle: F

last: Greenberg

first: Regina

last: Oshins

first: Karina

last: Serban

first: Timothy

last: Garrett

first: Mei

last: He


title: Total Progesterone Receptor (TPR) ChIPseq in the mouse myometrium at various stages of pregnancy, labour, and postpartum.

city: Toronto

first: Jennifer

last: Mitchell

state: Ontario

address: 25 Harbord Street

department: Cell and Systems Biology

institute: University of Toronto

summary: We have generated ChIPseq datasets for the total progesterone receptor (TPR) of the mouse uterine smooth muscle (myometrium) tissue. ChIP-seq experiments were conducted to evaluate changes in the regions bound by total progesterone receptor that occur as the smooth muscle cells transition from pregnancy to labour and postpartum using mouse myometrium tissue.

overall_design: ChIPseq for Total Progesterone Receptor (TPR) using mouse myometrium at gestational day 17 (D17), prelabour (PL),  term labour (LAB), and postpartum (D4PP) stages (n=2).

first: Nawrah

last: Khader

first: Andrew

last: Duncan


title: Blocking CK2α‐Bclaf1 Preserves Oligodendrocytes After Neonatal Hypoxic Injury

city: Tainan

first: Chih-Yen Wang

last: Wang

address: No.1, University Rd

department: Biotechnology and Bioindustry Sciences

country: Taiwan

institute: National Cheng Kung University

summary: Neonatal hypoxic injury is a common disorder that disrupts white matter development in newborns, with long-term impacts on cognitive and mental function. While oxygen availability controls oligodendrocyte (OL) differentiation, prolonged hypoxia leads to OL death and impairs subsequent myelination even after returning to normoxic conditions. In this study, we uncovered dual roles of the serine/threonine kinase CK2α and the transcriptional factor Bclaf1 in OL differentiation in an oxygen-dependent manner. Phosphorylated Bclaf1 by CK2α is essential for normal OL function. On the contrary, the CK2α-Bclaf1 axis drives hypoxia-induced OL apoptosis and alters the post-hypoxic myelination process. Importantly, inhibiting Bclaf1 activity with the acute treatment of clinically approved CK2 inhibitor silmitasertib and the herbal supplement curcumin protects OLs and restores myelin production in newborns following hypoxic injury. This approach unveils a key transcriptional mechanism in OL development and highlights a potential therapeutic strategy to mitigate neonatal hypoxic injury and prevent long-term mental health complications.

overall_design: P3 mouse pups and their nursing mother were placed in a chamber containing 10.5% oxygen. After an 8-day hypoxic incubation, the P11 mice were returned to a normoxic environment. The cortical tissue including corpus callosum from hypoxia and normoxia mice were harvested at P20 for RNA sequencing.

first: Wang

last: Chih-Yen