title: Epigenetic heterogeneity and state-specific transcriptional programs determine differential drug response in osteosarcoma [snRNAseq + snATACseq]

city: San Francisco

first: Alex

last: Lee

address: 1550 4th Street

institute: UCSF

summary: Osteosarcoma is a genomically complex tumor with structural rearrangements, aneuploidy, and chromosomal alterations, resulting in significant intertumoral heterogeneity. This complexity hampers the identification of key oncogenic pathways and subtypes. We hypothesized that chromatin accessibility could uncover molecular features to clarify their transcriptional programs, suggesting new therapies. Using ATAC-seq, H3K27ac profiling, and single-cell multiome analysis, we identified two distinct cellular states in osteosarcoma driven by unique transcription factor networks linked to normal bone development. These subtypes can be detected in patient samples via a specific gene expression signature with prognostic value.

overall_design: We utilized multiomic analysis single-nucleus  (snRNAseq + snATACseq) on two samples from PDX-derived cell lines to investigate the heterogeneity and transcriptional/epigenetic landscape of osteosarcoma. This study specifically aimed to address the enrichment of early osteoblast derived (EOD) and late osteoblast derived (LOD) clusters.

first: Eunice

last: López-Fuentes

first: Alejandro

last: Sweet-Cordero


title: Epigenetic heterogeneity and state-specific transcriptional programs determine differential drug response in osteosarcoma [ATAC-seq]

status: Public on Sep 29 2025

middle: G

state: CA

country: USA

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Patient derived xenographs (PDX), patient samples, PDX-cell lines and comercially available cell lines including the non-cancer hFOB1.19 osteoblast cell line were used. Nuclei was isolated and transposition was performed to generate the ATAC-seq libraries.


title: Inhibition of host N-myristoylation compromising the infectivity of SARS-CoV-2 due to Golgi-bypassing egress

city: Brisbane

first: Huiwen

last: Zheng

state: Queensland

address: The University of Queensland Brisbane

country: Australia

institute: The University of Queensland

type: Expression profiling by high throughput sequencing

summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused coronavirus disease 2019 (COVID-19) pandemic, remains a global health crisis despite vaccines, neutralizing antibodies, and antiviral drugs. Emerging mutations can reduce the effectiveness of these treatments, suggesting that targeting host cell factors may be a more robust strategy. Cellular N-myristoyltransferases (NMTs) are essential enzymes for protein myristoylation, affecting stability, interaction, localization, and function of numerous proteins involved in intracellular membrane trafficking. We demonstrate that selective inhibition of host cell NMT1 and -2 by IMP-1088 decrease SARS-CoV-2 infection by 90% in human lung and primary nasal epithelial cells, as well as in human 3D choroid plexus-cortical organoids. NMT1 and -2 inhibition does not affect viral entry, replication, or release, but instead impairs viral assembly and maturation, leading to compromised infectivity of released virions. We further show that inhibition of host NMT1 and -2 triggers an alternative Golgi-bypassing pathway for SARS-CoV-2 progeny virions release, which occurs through a lysosomal intermediate.

overall_design: 60 day-old choroid plexus organoids were dissociated and scRNAseq experiment was conducted in order to identify the abundance of neuronal and CP cell types.

first: Saber

middle: A

last: Elkader

first: Jessica

middle: C

last: Mar

first: Ernst

last: Wolvetang

first: Merja

last: Joensuu


title: DNA methylation patterns facilitate tracing the origin of neuroendocrine neoplasms

city: Heidelberg

first: Stephanie

last: Roessler

address: Im Neuenheimer Feld 224

country: Germany

institute: Heidelberg University Hospital

summary: Neuroendocrine neoplasms (NEN) are thought to originate from diffuse endocrine networks and therefore most frequently occur in the gastrointestinal tract and lungs. The liver is a frequent site of metastasis of NEN but also the presence of primary hepatic NEN has been proposed. Due to the impact on disease management, it is urgently required to discriminate the origin of hepatic NEN metastases and to identify clinically relevant subgroups.

overall_design: Using a comprehensive set of NEN (N=198), we showed that the DNA methylation profile of NEN of distinct anatomical localizations differed significantly and primary tumor-metastasis pairs clustered together, enabling us to identify the tumor origin.

first: Reka

last: Toth


title: Modulate spatial restriction of injury responses for cardiac repair

city: Beijing

first: Yifan

last: Xie

address: Mentougou District

country: China

institute: Fuwai Hospital

summary: Intrinsic molecular strategy at the organ level to injury stimuli remains elusive. Identifying and modulating such potential molecular strategy for systemic adaptations to injury is theoretically fascinating and therapeutically promising. Here, using integrative single-cell and spatial transcriptomic analysis, we reported that lysozyme 2 (Lyz2), a long-established myeloid marker, surprisingly indicated global injury status (across cell types and anatomic divisions) and influenced cardiac function after injury. We correlated the Lyz2 regulon of the lysosome-matrisome (particularly endocardial lysosomal-degrading Hspgs) with anatomical and functional relevance to cardiac injury and determined that such spatial model is consensus across various injury types, both mouse and human. Modulation of spatial model mediated by Lyz2 via genetic deletion or chemical inhibition in adult mice with myocardial infarction remarkably achieved immediate protective effects, a rare therapeutic benefit among current interventions for heart failure. These results provided the first molecular evidence for the unprecedented molecular strategy adopted by the heart with unparalleled therapeutic promising for organ repair.

overall_design: We leveraged single cell transcriptomics to overview molecular organization with anatomical divisions during cardiac regeneration. For single cell sequencing, heart tissue from the apical region of the ventricular was collected and pooled from 4 to 6 hearts. The study included six different time points, namely P1+(1dpr, 1dps, 4dpr, 4dps, 7dpr, 7dps) and P7+(1dpr, 1dps, 4dpr, 4dps, 7dpr, 7dps). Subsequently, the collected tissue underwent enzymatic digestion using the Neonatal Heart Dissociation Kit (Miltenyi Biotec) to obtain single cells. These single cells were then utilized for single cell RNA sequencing, specifically for the generation of single cell RNA-seq libraries. The Single Cell 3′ Reagent Kits v2 (10×Genomics) were employed in accordance with the manufacturer's instructions. After completing the capture and lysis procedures, cDNA synthesis and amplification were carried out according to the guidelines provided by the manufacturer (10X Genomics). The amplified cDNA obtained from each channel of the Chromium System was utilized for the construction of a sequencing library. This library was subsequently subjected to paired-end 150 bp sequencing on Hiseq X-ten (Illumina). As a result, a combined dataset consisting of 69,303 single cells and encompassing 30,905 genes was generated.

first: Chenghao

last: Fan

first: Shen

last: Song

first: Yu

last: Han

first: Dongcheng

last: Cai

first: Anteng

last: Shi

first: Fangfang

last: Wan

first: Jie

last: Feng

first: Jiajun

last: Zhong

first: Fei

last: Xu

first: Jiangping

first: Shengshou

last: Hu

last: Nie

first: Hui

last: Zhang


title: The translational landscape of mouse oocytes and preimplantation embryos revealed by high-resolution ribosome profiling

city: Gainesville

first: Zongliang

last: Jiang

state: FL

address: 2033 Mowry Rd

department: Animal Sciences

institute: University of Florida

summary: Translational regulation plays a critical role during oocyte and preimplantation embryo development. Here, we utilized high resolution ribosome fractionation and low-input ribosome profiling of mouse oocytes and preimplantation embryos to explore the translational landscapes of early embryo development. The inconsistency was observed when comparing polysome-bound, monosome-bound, and free RNA profiles, indicating the role of ribosomes in manipulating RNA fate, especially for oocyte-to-embryo transition (OET) and zygotic genome activation (ZGA). Moreover, eif1ad3 with its homologs, including eif1ad4, eif1ad6, eif1ad7, etc. are highly translated during ZGA and regulating the translational activity of other genes. Knocking down these genes lead to defective ZGA and preimplantation development. These data reveal that the transcriptome and translatome manipulate RNA fate collectively to regulate mouse preimplantation development.

overall_design: Ten equal fractions of ribosome fractionation were recovered from 100 oocytes (GV or MII oocyte) or embryos at different developmental stages (zygote, 2-, 4-, 8-cell, morula, and blastocyst) and subjected to RNA isolation,  followed by RNA-sequencing analysis. Also, a pool of 20 oocytes or preimplantation embryos (n=4) selected from the same batch in each developmental stage used for ribosome profiling were used to profile transcriptomes by RNA-seq following Smart-seq2 protocol.

first: Zongliagn

first: Hao

last: Ming

first: Rajan

last: Iyyappan

first: Andrej

last: Susor


title: Treg-microglia partnership in the injured spinal cord preserves Treg cells function and regulates microglial cholesterol metabolism

city: nanjing

first: tao

last: qin

address: hanzhong road 104

institute: The First Affiliated Hospital of Nanjing Medical University

summary: The quantitative variations and specific roles of regulatory T cells (Treg cells) within spinal cord injury (SCI) remain elusive. Utilizing single-cell RNA sequencing, flow cytometry, and immunofluorescence, we discovered that Treg cells began to infiltrate the injured spinal cords in mice approximately three days after SCI. Selective depletion of Treg cells resulted in an expansion of the injury area, reduction in neuronal survival, and a decrease in long-term functional recovery post-SCI. Transcriptomic analyses of Treg cells unveiled potent anti-inflammatory functions and the potential to influence neighboring immune cells within the spinal cord after SCI. Adoptive transfer of Treg cells demonstrated measurable improvement in SCI recovery and increased neuronal retention in mice. However, selective depletion of microglia inhibited the neuroprotective effects of Treg cells, indicating that the effect of Treg cells in the spinal cord depends on the presence of microglia. Mechanistically, Treg cells promoted spinal cord functional recovery by upregulating microglial Abcg1 receptor expression, enhancing cholesterol transport, reducing microglial lipid droplet formation, and moderating the M1 phenotype after SCI. In summary, our study elucidates the spatiotemporal distribution of Treg cells after SCI and their unique transcriptomic features, clarifying the impact of Treg cells on microglial cholesterol metabolism and inflammatory phenotype. These findings indicate that Treg cells may serve as a potential target for SCI treatment.

overall_design: In an endeavor to elucidate the specific mechanisms through which Treg cells exert their neuroprotective functions, we isolated Treg cells from both the injured spinal cord and spleen at 14 days post-SCI (the peak of Treg cell quantity), and conducted bulk RNA sequencing;  To investigate the potential influence of Treg cells on microglia within the spinal cord, we conducted co-culture between Treg cells and microglia,and microglia were then collected from both groups for bulk RNA-seq analysis, utilizing unstimulated primary microglia as the control group.

first: Tao

last: Qin

first: Zihan

last: Zhou

first: Zhenqi

last: Yang


title: Effect of conditional triple-knockout of Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c or overexpression of KDM4C/JMJD2C mutants with different phase separation ability on gene expression in mouse embryonic stem cells. [HiChIP]

city: Guangzhou

first: Xinyi

last: Liu

state: Guangdong

address: No. 74, 2nd Zhongshan Road

institute: Sun Yat-Sen University

summary: To investigate the functions of JMJD2/KDM4 family in mouse embryonic stem cells (mESCs), we treat the the conditional triple-knockout  mESCs of Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c with 4-hydroxytamoxifen (4-OHT) for 72h. Besides, to investigate whether JMJD2/KDM4 phase separation affects Enhancer-Promoter loops, we generated IDR-truncated JMJD2C/KDM4C (Mut) to disrupt its phase separation ability, and rescued it by by fusing two IDRs in other species (hIDR1 and hIDR2). Further, to investigate whether the functions of JMJD2/KDM4 are catalytic-dependent, we also generated catalytic mutants of JMJD2B and JMJD2C. We overexpressed those phase separation or catalytic mutants in the aboved mESCs separately and TKO endogenous Jmjd2 by adding 4-OHT 72h (for phase separation mutants) or 36h (for catalytic mutants).

overall_design: We then performed H3K27ac HiChIP analysis using data obtained from 9 different cells (Ctrl (WT mESC), JMJD2 TKO, JMJD2C Mut (IDR truncated), Mut-hIDR1 (rescued by hIDR1, from human HNRNPA), hIDR1, Mut-hIDR2 (rescued by hIDR2, from human FUS), hIDR2, CMuts (rescued by catalytic mutants of JMJD2B and JMJD2C) and EV (empty vector, negative control of CMuts).

first: Shaoshuai


title: Epigenetic heterogeneity and state-specific transcriptional programs determine differential drug response in osteosarcoma.

first: Alex

last: Lee

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

overall_design: Refer to individual Series


title: Single-cell RNA sequencing of lung tissues from non-irradiated wild-type, irradiated conditional knockout with drug treatment, and irradiated wild-type mice

status: Public on Sep 28 2025

city: Seoul

first: Yoon-Jin

address: Nowon GU

country: South Korea

institute: Korea Institute of Radiological & Medical Sciences

summary: This dataset provides scRNA-seq profiles of lung tissues from three experimental groups: non-irradiated wild-type controls, irradiated conditional knockout mice treated with drug, and irradiated wild-type mice. The data enable analysis of radiation-induced lung injury, gene expression reprogramming, and the modulatory role of both conditional gene deletion and pharmacological intervention.

overall_design: Lung tissues were collected from three groups of mice: 1.Non-irradiated wild-type mice (control) : NoIR2 2.Irradiated conditional knockout mice treated with drug : KO 3.Irradiated wild-type mice : WT

first: Jeeyong

first: Jae-Kyung

last: Nam


title: Epigenetic heterogeneity and state-specific transcriptional programs determine differential drug response in osteosarcoma [RNA-seq]

overall_design: RNA-seq libraries were performed from osteosarcoma PDX-derived cell lines and commercially available osteosarcoma cell lines grown in normal conditions.

first: Eunice

last: López-Fuentes

first: Alejandro

last: Sweet-Cordero


title: Urinary extracellular vesicles for high-precision bladder cancer subtyping and prognosis

first: Mei

last: He

address: 2033 Mowry Rd, Cancer and Genetics Research Complex

department: Pharmaceutics

summary: Bladder cancer exhibits molecular heterogeneity that complicates early diagnosis and prognosis, and drives confounding clinical outcomes. Non–muscle invasive and muscle-invasive subtypes, especially for intermediate to high grade, carry a 25 – 50% progression-free survival rate, underscoring the need for high precision prognostic strategy. Urinary extracellular vesicles (uEVs) are promising carriers of tumor-derived RNAs and proteins. However, significant challenges in studying uEVs arise from the diverse cellular origin of uEVs associated with the dynamic composition of urine, which presents roadblocks for developing the clinical utility of uEVs. We introduced an AI-driven EV liquid biopsy pipeline that integrates (1) standardized EV isolation via NanoPom magnetic beads, (2) transcriptomic profiling for molecular subtyping, and (3) prognostic scoring algorithm. In a discovery cohort of 16 bladder cancer patients including both MIBC and NMIBC, we compared NanoPom isolated uEVs with ExoEasy and Fujifilm MagCapture isolated uEVs, for identifying bladder cancer subtype-specific gene signatures, and externally validated them using UCSC Xena. The result outperformed currently reported bladder cancer diagnostic biomarkers from assays including Galeas, CxBladder, and Xpert. In a validation cohort of matched 7 patient plasma samples, we confirmed with plasma derived EVs for correlating with urinary EV biomarkers from NGS sequencing. The prognostic score stratified patients into low-, intermediate-, and high-grade risk groups based on Xena's bladder cancer survival outcomes. Our AI-driven uEV liquid biopsy pipeline proves the concept for high precision bladder cancer subtyping and prognosis, which could potentially facilitate treatment decision and lead to advanced profiling of bladder tumor biology using uEV liquid biopsy.

overall_design: A total of 23 samples (16 patients for discovery using urine , 7 patients for validation using plasma) corresponding to bladder cancer patients or healthy individuals underwent next generation sequencing for transcriptomic analysis after EV isolation by the NanoPoms.

first: Zachary

middle: F

last: Greenberg

first: Tarun

last: Hutchinson

first: Jonathan

last: Kahn

first: Kiley

middle: S

last: Graim

first: Padraic

last: O'Malley


title: Sequential transcriptional gates in the thalamo-cortical circuit support memory stabilization [ChIP-seq]

city: New York

first: Richard

last: Koche

state: New York

institute: Memorial Sloan Kettering Cancer Center

summary: The molecular mechanisms that enable memories to persist over long time-scales from days to weeks and months are still poorly understood. To develop insights, we created a behavioral task where by varying the frequency of learned associations, mice formed multiple memories, but only consolidated some while forgetting others, over the span of weeks. We then monitored circuit-specific molecular programs that diverge between consolidated and forgotten memories. We identified multiple distinct waves of transcription, i.e., cellular macrostates, specifically in the thalamo-cortical circuit, that defined memory persistence. Notably, a small set of transcriptional regulators appeared sufficient to orchestrate broad molecular programs that enabled entry into these macrostates. Targeted CRISPR-manipulations of these transcriptional regulators revealed that while they had no effects on memory formation, they had prominent, causal, and strikingly time-dependent roles in memory stabilization. In particular, the calmodulin-dependent transcription factor Camta1 was required for initial memory maintenance over days, while Tcf4 and the histone methyl-transferase Ash1L were required later to maintain memory over weeks. These results identify a critical Camta1-Tcf4-Ash1L thalamo-cortical transcriptional cascade required for memory stabilization, and puts forth a model where the sequential, multi-step, recruitment of circuit-specific transcriptional programs enable memory maintenance over progressively longer time-scales.

overall_design: ChIP sequencing of sorted neurons (NeuN-Ax488 antibody; Millipore, #MAB377X) from mouse brains after experiencing control or behavioral training conditions.

first: Andrea

last: Terceros

first: Celine

last: Chen

first: Priya

last: Rajasethupathy


title: Epigenetic heterogeneity and state-specific transcriptional programs determine differential drug response in osteosarcoma [Cut&Run]

overall_design: Osteosarcoma cell lines derived from xenographs were used in this study. H3K27ac was profiled by CUT&RUN. IgG was used as control per sample. 2-5 replicates were performed per sample.


title: Bile Acid Analogs with Anti-germination Activities for Prophylaxis of Clostridioides difficile Infection Alter Bile Acid Homeostasis in the Enterohepatic Cycle

city: Detroit

first: Wanqing

state: MI

address: 6135 Woodward Ave

department: Eugene Applebaum School of Pharmaceutical Sciences

institute: Wayne State University

summary: We previously reported that two bile acid (BA) analogs CamSA and CA-Quin demon-strate potent anti-germination activity against Clostridioides difficile (C. difficile) spores, protecting rodents from C. difficile infections. Here we further evaluated the impact of these analogs on the hepatic transcriptome and BA homeostasis in vivo by focusing BA profiles on the liver, feces, and chyme as well as hepatic transcriptome after a 7-day treatment. The two compounds demonstrated similar impact on BA profiles among the three samples, with significantly increased BA excretion in feces. This change is aligned with significantly altered expression of genes involved in BA homeostasis in both liver and gut tissues. Also, both compounds increased levels of unconjugated BAs in the feces, indicating an elevated activity of gut microbiota (GM). Notably, fecal levels of anti-c. difficile germination chenodeoxycholate and pro-germination taurocholate are signifi-cantly increased and decreased by the treatments, respectively. While hepatic tran-scriptome did not show significant toxicity, altered genes are enriched in pathways as-sociated with GM activity and lipid metabolism. Overall, our study suggests that in vivo CamSA and CA-Quin treatment demonstrated minimal hepatoxicity but significantly altered BA homeostasis and potentially favorable improvement for GM profiles that together inhibit C. difficle germination.

overall_design: RNA-seq of profiling of liver tissue from mouse livers of mice treated with either DMSO (control) or CamSA (treatment) or CA-Quin (treatment) after 7 days of treatment.

first: Nivisa

last: Vakeesan

first: Efren

last: Heredia

first: Chandler

last: Hassan

first: Yang

last: Jiang

first: Shiv

last: Sharma

first: Lianyong

last: Su

first: Huiping

last: Zhou

first: Steven

last: Firestine

first: Ernesto

last: Abel-Santos


title: Isobavachalcone ameliorates TNBS-induced Crohn’s disease-like colitis via GPR84-PI3K-AKT axis

city: NANCHANG

first: yuchang

last: sun

address: Xinqizhou Dong Avenue, Ganjiang New

institute: Ganjiang Traditional Chinese Medicine Innovation Center

summary: Ethnopharmacological relevance The traditional Chinese medicine Psoralea corylifolia L. (PCL) has been clinically used to treat diarrhea and gastrointestinal inflammatory disorders. G protein-coupled receptor 84 (GPR84) is emerging as a potential target for inflammatory bowel disease (IBD). Pharmacological investigations confirm the efficacy of PCL against IBD, but its active components targeting GPR84 and their mechanisms remain unclear. Aim of the study We aimed to identify active components from PCL against GPR84, evaluate their therapeutic effects and elucidate their mechanisms of action in IBD treatment.


title: Sequential transcriptional gates in the thalamo-cortical circuit support memory stabilization [ATAC]

overall_design: ATAC sequencing of sorted neurons (NeuN-Ax488 antibody; Millipore, #MAB377X) from mouse brains after experiencing control or behavioral training conditions.


title: Long-acting STK25 antisense oligonucleotide as a therapeutic candidate for MASLD

city: Kunming City

first: yifeng

last: qin

state: Yunnan Province

address: School of Life Science, Yunnan University, Chenggong District

institute: yunnan university

summary: Metabolic dysfunction–associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder worldwide and a leading cause of liver-related morbidity. Insulin resistance and hepatic lipid metabolism dysfunction are recognized as central pathological mechanisms, yet no therapy is currently approved specifically for MASLD. Antisense oligonucleotides (ASOs) are single-stranded nucleotide drugs with high target specificity and long-lasting activity, making them well suited for chronic metabolic diseases. Here, we describe a novel ASO candidate targeting serine/threonine kinase 25 (STK25), a lipid droplet–associated kinase implicated in MASLD pathogenesis. In three human cell lines, the ASO (c337) robustly reduced STK25 expression. For in vivo validation, we generated Gc337 by GalNAc conjugation to enable liver-specific delivery. In a high-fat diet-induced MASLD mouse model, Gc337 significantly improved insulin sensitivity, reduced hepatic lipid accumulation, and lowered body weight, with efficacy comparable to resmetirom, the only FDA-approved therapy for metabolic-associated steatohepatitis. A single injection sustained >50% hepatic Stk25 knockdown for 35 days without hepatotoxicity, underscoring its long-acting therapeutic profile. Importantly, c337 was designed to avoid all known single-nucleotide polymorphisms (SNPs), ensuring efficacy across genetically diverse populations. Together, these findings establish Gc337 as a durable, SNP-aware, and clinically translatable nucleic acid–based therapeutic candidate for MASLD.

overall_design: In a high-fat diet-induced MASLD mouse model, mice were treated with either resmetirom or STK25 knockdown using Gc337. After the treatment period, liver tissues were collected for sequencing analysis.


title: Impact of radiation dose and time since radiation exposure on host-microbe relationship

city: Silver Spring

first: Aarti

last: Gautam

state: MD

address: 503 Robert Grant Avenue

department: Medical Readiness Systems Biology

institute: WRAIR

summary: The microorganisms that colonized in or on hosts play significant roles in regulating host’s immunological fitness and bioenergy production, thus controls the host’s response to stress or foreign stimuli. Since radiation typically causes a pro-inflammatory and bioenergy expensive condition, we speculate that the radiation could influence gut microbial compositions, thereof the host-microbe bidirectional relationship. Pertinent model included exposing the young adult mice to total body irradiation (TBI) at doses of 9.5Gy and 11Gy, respectively. Descending colon contents (DCC) were collected from non-irradiated mice (baseline control), and irradiated mice euthanized on days 1, 3 and 9 post-TBI. DCC’s 16s ribosomal DNAs were screened for bacterial taxonomic classification and bacterial abundance profile informed metagenome-specific biofunctions. A second aliquot of same DCC was screened for untargeted metabolomics assay to find most perturbed metabolite-enriched networks. Dose-independent temporal delay since TBI emerged as the primary factor explaining the increased richness of bacterial community and the diversity of metabolite landscape. Among the mice exposed to 11Gy TBI, an increased abundance of Firmicutes, an anti-inflammatory and efficient energy harvesting bacteria accompanied an increment of pro-inflammatory Deferribacteres. Systems evaluation of the functional networks linked to DCC’s metagenome and metabolite, respectively, suggested a diverging trend between host and DCC microbes in regulating the network clusters, such as lipid metabolism, bioenergy synthesis, particularly at the later time points post-11Gy TBI. This analysis potentially suggested a disrupted symbiotic relationship between the host and microbes when the host became moribund.

overall_design: 38 samples with different amounts of radiation and time points

first: Nabarun

last: Chakraborty

first: Allison

last: Hoke

first: Ross

last: Campbell

first: Gregory

last: Holmes-Hampton

first: Vidya

middle: P

last: Kumar

first: Candace

last: Moyler

first: Rasha

last: Hammamieh

first: Sanchita

last: Ghosh


title: Effect of conditional triple-knockout of Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c or overexpression of KDM4C/JMJD2C mutants with different phase separation ability on gene expression in mouse embryonic stem cells. [ChIP-Seq]

first: Xinyi

last: Liu

summary: To investigate the functions of JMJD2/KDM4 family in mouse embryonic stem cells (mESCs), we treat the the conditional triple-knockout  mESCs of Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c with 4-hydroxytamoxifen (4-OHT) for 72h. Further, to investigate whether JMJD2/KDM4 phase separation affects chromatin binding of YY1, we generated IDR-truncated JMJD2C/KDM4C (Mut) to disrupt its phase separation ability, and rescued it by by fusing two IDRs in other species (hIDR1 and hIDR2). We overexpressed those phase separation mutants in the aboved mESCs separately and TKO endogenous Jmjd2 by adding 4-OHT 72h.

overall_design: We then performed ChIP-seq of JMJD2A/KDM4A in WT mESC. Besides, we perform ChIP-seq of YY1, H3K27ac and H3K9me3 before and after JMJD2 TKO. Further, we perform ChIP-seq of YY1 in other 6 different cells (JMJD2C FL (Full length), JMJD2C Mut (IDR truncated), Mut-hIDR1 (rescued by hIDR1, from human HNRNPA), hIDR1, Mut-hIDR2 (rescued by hIDR2, from human FUS), hIDR2 with TKO of endogenous Jmjd2.

first: Shaoshuai

last: Jiang


title: Effect of conditional triple-knockout of Jmjd2a/Kdm4a, Jmjd2b/Kdm4b and Jmjd2c/Kdm4c or overexpression of KDM4C/JMJD2C mutants with different phase separation ability on gene expression in mouse embryonic stem cells. [4C-Seq]

summary: We establish Enhancer-Promoter loop of Dppa5a in pre-iPSC by a chemical-inducible system to promote the establishment of pluripotency.

overall_design: The SadCas9-ABI and SpdCas9-PYL , both fused with IDR-truncated mutant of JMJD2C (Mut), Mut-hIDR1 or hIDR1, were targeted to enhancer and promoter of Dppa5a. We induced fusion of JMJD2 phase at enhancer and promoter of Dppa5a by adding ABA for 96h and washed-out. The E-P loop of Dppa5a was evaluated at 168h by 4C-seq with bait in the promoter region of Dppa5a.


title: Multiomics Analyses Unveil Immune Landscape in Pediatric and Adult Sepsis [CITE-seq]

city: chongqing

first: Ye

last: qian

address: No. 1 Youyi Road, Yuzhong District, Chongqing

institute: The First Affiliated Hospital of Chongqing Medical University

summary: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune response varies significantly based on the anatomical source of infection.  This study uses cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to profile surface protein expression and transcriptomics at the single-cell level in PBMC samples from 40 adults: 3 healthy controls, 5 ICU controls, and 32 sepsis patients. The sepsis patients are categorized by infections originating from different anatomical sites. The findings aim to support sepsis stratification and guide the development of targeted therapies based on infection sources.

overall_design:
Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples collected from healthy adult controls, adult ICU controls, adult sepsis patients. CITE-seq was conducted to simultaneously measure surface protein expression and gene expression at the single-cell level.

***************************************************************
The raw sequencing have been uploaded to China Genomic Sequence Archive with accession number GSA:HRA008452.
***************************************************************

first: Qian

last: Ye

first: Fang

last: Xu

first: Ju

last: Cao


title: Multiomics Analyses Unveil Immune Landscape in Pediatric and Adult Sepsis [bulk RNA-seq]

summary: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune response varies significantly based on the anatomical source of infection. This study investigates the transcriptomic profiles associated with sepsis using bulk RNA sequencing. A total of 207 PBMC samples were analyzed, including those from healthy adults, adult ICU controls, adult sepsis patients, healthy children, pediatric ICU controls, and pediatric sepsis patients. The analysis of this dataset reveals both shared and source-specific gene expression patterns, providing insights into the molecular mechanisms underlying sepsis and informing the development of targeted therapeutic strategies.

overall_design:
Total RNA was extracted from PBMCs isolated from blood samples collected from healthy controls, ICU controls, and sepsis patients. The sepsis patients were classified based on infection origins from various anatomical sites, including the abdomen, respiratory tract, urinary tract, skin, and central nervous system (CNS). Bulk RNA sequencing was conducted to capture global gene expression profiles.

***************************************************************
The raw sequencing have been uploaded to China Genomic Sequence Archive with accession number GSA:HRA008452.
***************************************************************


title: ADAM17 in glutamatergic presympathetic neurons enhance angiotensin II-induced disinhibition and sympatho-excitation through microglia and chemotactic pathway

city: Xi’an

first: Jiaxi

address: 76 West Yanta Road

institute: Xi’an Jiaotong University

summary: Background: Neuron-expressing ADAM17 (a disintegrin and metalloprotease 17) has been shown to support sympatho-excitation and salt-sensitive hypertension. The aim of current work was to identify by what mechanism ADAM17 in glutamatergic neurons support activation of presympathetic neurons (PSN). Methods: Both acute Ang-II stimulation in the PVN (paraventricular nucleus) and DOCA (deoxycorticosterone acetate)-salt model were utilized for electrophysiological recording and blood pressure (BP) recording, in mice with ADAM17 selective knockout in glutamatergic neurons (A17G), and ADAM17 targeted knockout in certain glutamatergic PVN-RVLM (rostral ventrolateral medulla) projecting neurons (PSN-A17G). Results: Both Ang-II and DOCA-salt treatment markedly decreased GABAergic inhibitory tone in the PVN of WT (wild-type) mice. Post DOCA-salt treatment, microglia were activated in the PVN, with significantly more expression of CD68 and related cytokines. With 7-day of DOCA-salt treatment, before BP arrived its plateau, PVN microglia had already been activated, and they were spotted more closely to virus-labeled glutamatergic PSN. Moreover, the number of GABAergic presynaptic terminals, locating on the soma area of PSN, was markedly reduced. In both A17G and PSN-A17G, these DOCA-salt-associated changes were blunted. Further experiments revealed that Ang-II promotes neuron-mediated chemotaxis for microglia, and this effect in neurons involved ADAM17 and its downstream – CX3CL1/CX3CR1 chemotactic pathway. Pharmacologically blocking CX3CR, or inhibiting migration of microglia, confirmed the contribution of CX3CL1/CX3CR1 signaling pathway and microglial displacement to Ang-II-induced disinhibition and activation of PSN.

overall_design: To investigate the effect of ADAM17 knockout in glutamergic neurons on gene expression in the paraventricular nucleus of hypothalamus

first: Jiawei

last: Wang

first: Rui

last: Yang

first: Hanxue

last: Wu


title: Profiling non-human primate exosomal RNA to understand the legacy of early life stress

city: Los Angeles

first: Brian

middle: George

last: Dias

address: 4650 Sunset Blvd

department: Division of Endocrinology

institute: Children's Hospital Los Angeles

summary: Motivated to identify novel molecular pathways and processes that are enduringly perturbed as a consequence of childhood maltreatment, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques. RNA sequencing revealed that macaque plasma EVs contain RNA aligned to the microbiome.

overall_design: We performed total RNA sequencing of the content of extracellular vesicles purified from rhesus macaque plasma

first: Laura

last: Korobkova

first: Matthew

last: E Thornton

last: Collin

first: Elyse

middle: L

last: Morin

first: Had

last: j Aoued

first: Soma

last: Sannigrahi

first: Kristie

middle: M

last: Garza

first: Erin

middle: R

last: Siebert

first: Hasse

last: Walum

first: Ryan

last: Cabeen

first: Brendan

middle: H

last: Grubbs

first: Mar

last: Sanchez


title: Non-canonical roles of Keap1/Nrf2 in regulating quiescence and early activation in adult muscle stem cells [RNA-Seq]

city: Hong Kong

first: Lifang

last: HAN

address: 6202D, Clear Water Bay

department: LIFS

institute: HKUST

summary: Adult muscle satellite cells (MuSCs) are mostly quiescent in uninjured muscles under normal homeostasis. Although several mechanisms underlying quiescence maintenance are known, our understanding of the process remains incomplete. Here, we show that Keap1 regulates MuSC quiescence maintenance by promoting Nrf2 protein degradation. Inducible deletion of Keap1 activates MuSCs to different extent in a sex-specific manner via differential Nrf2 protein levels: in Keap1-null MuSCs from male mice, Nrf2 protein is at an intermediate level due to the action of a GSK3beta-dependent Nrf2 degradation system, which promotes mutant MuSCs to enter a GAlert-like state; in Keap1-null MuSCs from female mice, the loss of Keap1 together with estrogen-mediated GSK3beta inactivation renders Nrf2 at its highest level, which induces the expression of multiple metabolic genes resulting in metabolic reprogramming, spontaneous activation and gradual depletion of MuSCs. Consistently, interference of selected Nrf2-regulated metabolic genes impairs early activation of MuSCs. Thus, Keap1/Nrf2 regulates quiescence maintenance and early activation of MuSCs independently of its canonical roles in the antioxidant response.

overall_design: To understand why Keap1/Nrf2 signaling regulate MuSC maintenance and activation in a gender-dependent manner, we freshly isolated MuSCs from Keap1 Hetz and KO female and male mice.

last: Han

first: Zhenguo


title: Non-canonical roles of Keap1/Nrf2 in regulating quiescence and early activation in adult muscle stem cells [ChIP-Seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for Nrf2 in freshly isolated Keap1-null and Nrf2-null muscle satellite cells


title: Non-canonical roles of Keap1/Nrf2 in regulating quiescence and early activation in adult muscle stem cells

overall_design: Refer to individual Series


title: Hand1 KO HAND2 replacement RNA-Seq data

city: Indianapolis

first: Anthony

last: Firulli

email: tfirulli@iupui.edu, tfirulli@iu.edu

state: IN

address: 1044 W Walnut R4302E

department: pediatrics

institute: IU school of medicine

summary: This is an analysis of E9.5 mouse yold sacs from control, HAND1 loss-of-function, and HAND2 replacement mice

overall_design: E9.5 yolk sac (YS) RNA was evaluated 4 control (H1^fx/+) 3 H1CKOs, and 4 H1^H2/H2 replacement allele YS

first: Beth

middle: B


title: Tissue miRNA expression profile in patients with cholangiocarcinoma(CCA) and its corresponding adjacent tissue

city: Jinan

first: Shu

middle: Li

last: zhuang

state: China/Shandong

address: Department of General Surgery, Qilu Hospital, Shandong University, 107, Jinan Culture Road, Jinan, 250012, China.

department: Qilu Hospital

institute: Shandong University

type: Non-coding RNA profiling by high throughput sequencing

summary: Cholangiocarcinoma (CCA), consisting of three subtypes-intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA), is a type of highly aggressive cancer arising from the biliary system and has an extremely poor prognosis. Through tissue miRNA sequencing, we screened out the  differentially expressed miRNA in patients with  3 perihilar cholangiocarcinoma(pCCA) and 3 distal cholangiocarcinoma(dCCA)  and  its corresponding adjacent tissue.

overall_design: Tissue miRNA expression profiling from 3 perihilar cholangiocarcinoma(pCCA) and 3 distal cholangiocarcinoma(dCCA) and  their corresponding adjacent tissues was detected by high throughput sequencing.

first: Zongli

last: Zhang

first: Yunfei

last: Xu

first: Lizhuang

last: Shu


title: Transcriptomic profile and validation of the protective role of celecoxib on cirrhotic splenomegaly

city: Chengdu

first: Shihang

last: Tang

address: GUOXUE 37

institute: West China hospital

summary:
Splenomegaly can exacerbate liver cirrhosis and portal hypertension. We have previously demonstrated that cyclooxygenase-2 (COX-2) inhibitor can attenuate cirrhotic splenomegaly. However, the mechanism of cirrhotic splenomegaly remains unclear and is the focus of this study.
Material and methods: Intraperitoneal injection of thioacetamide (TAA) was used to induce cirrhotic splenomegaly. Thirty rats were randomized into the control group. TAA and TAA+Celecoxib groups. Splenic gene profiling was analyzed by high-throughput RNA sequencing. Histological analysis of spleen tissue was evaluated by H&E, Sirius red, Prussian blue staining, and transmission electron microscopy. The splenic mRNA levels of collagen III and α-SMA and splenic contents of Ki-67, VEGF, IL-6, and TNF- were quantified.
Results: A total of 1461 differentially expressed genes (DEGs) were identified in the spleens of the TAA group compared to the control group. The immune response and immune cell activation might be the major signaling pathways involved in the pathogenesis of cirrhotic splenomegaly. With its immunoregulatory effect, celecoxib can ameliorate cirrhotic splenomegaly and liver cirrhosis. Furthermore, 304 coexisting DEGs were obtained between TAA vs. control and TAA+celecoxib vs. TAA. According to GO and KEGG analyses, celecoxib may attenuate cirrhotic splenomegaly by suppressing splenic immune cell proliferation, inflammation, immune regulation, and fibrogenesis. The impacts of celecoxib on splenic immune cell proliferation, inflammation, immune regulation, and extracellular matrix were then validated by the decreased splenic Ki-67-positive cells, macrophages, fibrotic areas, and mRNA levels of collagen III and α-SMA.
Conclusions: Celecoxib attenuates cirrhotic splenomegaly by inhibiting splenic immune cell proliferation, inflammation, and fibrogenesis. The current study sheds light on the therapeutic strategy of liver cirrhosis by targeting splenic abnormalities and provides COX-2 inhibitors as a novel medical treatment for cirrhotic splenomegaly.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for spleens from control group, TAA group and TAA+Celecoxib group

first: Yanting

last: Ye

first: Yang

last: Tai

first: Chong

last: Zhao

first: Zhiyin

last: Huang

first: Chengwei

first: Jinhang

last: Gao


title: Dorsal Root Ganglion-Mediated Modulation of Neuroinflammation and Neurovasodilation in Rosacea by Gabapentin

status: Public on Sep 27 2025

city: Boston

first: SangGyu

last: Lee

state: Massachusetts

address: 14 Isabella St, #G

institute: Massachusetts General Hospital

summary: Neurogenic rosacea features disproportionate pain and erythema resistant to conventional treatments. While gabapentin shows clinical efficacy, its molecular mechanism remains undefined.Using a murine rosacea model induced by LL37, we performed bulk RNA sequencing and molecular analyses of skin and dorsal root ganglia (DRG) to assess gabapentin's effects. LL37 triggered parallel neuroimmune and neurovascular activation in skin and DRG, including upregulating of Th2, IGF, CGRP, and nitric oxide synthases. Gabapentin suppressed CGRP expression, NF-κB phosphorylation, and neurovascular remodeling, particularly in DRG and skin. Transcriptomic and protein analyses revealed that gabapentin modulates neuronal excitability and inflammatory signaling via GABAergic and calcium channel pathways. Gabapentin exerts anti-neuroinflammatory and anti-neurovascular actions via DRG-mediated pathways in rosacea. These findings identify the peripheral nervous system as a central therapeutic target and establish gabapentin’s molecular rationale in treating neurogenic skin inflammation.

overall_design: Female BALB/c mice (6 weeks old) were treated with intradermal LL37 (320 μM, 40 μL, twice daily for 2 days). Gabapentin (100 mg/kg in water, oral, twice daily) was administered from day 3. On day 4, dorsal root ganglion tissue was collected for RNA sequencing.


title: Integrin/CD44-Targeted Liposomal Co-Delivery of Nintedanib and Dexamethasone for Acute Exacerbation of Idiopathic Pulmonary Fibrosis

city: Nanjing

first: Xinmei

address: No.321 Zhongshan Road

institute: Nanjing Drum Tower Hospital

summary: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) poses a significant clinical challenge due to its high morbidity and mortality, coupled with a lack of effective targeted therapies. Here, utilizing single-cell transcriptomic analysis, we identified integrin and CD44 as markedly upregulated in injured alveolar type II cells and myofibroblasts, highlighting their potential as pathological delivery targets in AE-IPF. Based on these findings, we developed a dual-targeted liposomal nanoplatform (ND-RHL) co-encapsulating nintedanib and dexamethasone, specifically engineered to exploit integrin/CD44 overexpression for pulmonary precise drug delivery and synergistic anti-fibrotic and anti-inflammatory effects. ND-RHL exhibited favorable physicochemical characteristics, efficient dual-drug loading, and selective accumulation in integrin/CD44-high cells both in vitro and in vivo. In a murine model of AE-PF, intratracheal administration of ND-RHL markedly improved survival, mitigated lung inflammation and fibrosis, and preserved pulmonary architecture, with minimal systemic toxicity. Mechanistically, transcriptomic profiling and immune phenotyping demonstrated that ND-RHL reversed AE-induced gene expression patterns and inhibited pivotal signaling pathways, including PI3K–AKT–mTOR, Wnt/β-catenin, and NF-κB–PPARγ, thereby orchestrating the remodeling of both immune and extracellular matrix microenvironments. This study presents ND-RHL as a mechanistically informed, cell-targeted nanotherapeutic with robust therapeutic potential and translational promise for the treatment of AE-IPF and related fibrotic lung diseases.

overall_design: RNA-seq profiling of lung tissues from saline-treated mice (control), AE-PF mice, and ND-RHL-treated AE-PF mice

first: Yingwei

first: Mengshu

last: Cao

first: Yonglong

last: Xiao


title: Bile exosome miRNA expression profile in patients with perihilar cholangiocarcinoma(pCCA) and common bile duct stones(CBDS)

summary: Cholangiocarcinoma (CCA) is a type of highly aggressive cancer arising from the biliary system. Through bile exosome miRNA sequencing, we screened out the  differentially expressed miRNA in patients with perihilarl cholangiocarcinoma(pCCA) and common bile duct stones(CBDS).

overall_design: Bile exosome miRNA expression profiling from 3 pCCA and 3 CBDS patients was dected by high throughput sequencing.


title: Bile exosome miRNA expression profile in patients with distal cholangiocarcinoma(dCCA) and common bile duct stones(CBDS)

summary: Cholangiocarcinoma (CCA) is a type of highly aggressive cancer arising from the biliary system. Through bile exosome miRNA sequencing, we screened out the  differentially expressed miRNA in patients with distal cholangiocarcinoma(dCCA) and common bile duct stones(CBDS).

overall_design: Bile exosome miRNA expression profiling was dected by high throughput sequencing.


title: High-throughput sequencing data related to JMJD2/KDM4 phase separation (LoopID)

first: Xinyi

last: Liu

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


title: IGFBP2 Mediates Human iPSC-Cardiomyocyte Proliferation in a Cellular Contact-Dependent Manner

city: Suwon-si

first: Soah

state: Geonggi-do

address: 2066 Seobu-ro, Jangan-gu, 530502

department: Pharmacy

institute: Sungkyunkwan University

summary: Rationale: Inducing cardiomyocyte proliferation in situ is an attractive approach for achieving cardiac regeneration after myocardial injury. However, numerous inhibitory mechanisms are present in cardiomyocytes that silence the pro-proliferative signals for their expansion. We hypothesized that cell-cell contact exerts a major suppressive effect on cardiomyocyte proliferation.  Objectives: This study aims to uncover the molecular mechanisms underlying cell contact-mediated inhibition of cardiomyocyte proliferation and leverage this knowledge to sustain proliferation of cardiomyocytes in 3D despite cell-cell contact.  Methods and Results: Using human iPSC-derived cardiomyocytes (hiPSC-CMs) as a model system, we found that the proliferative capacity of hiPSC-CMs is initially increased proportional to cell density until cells form intercellular contacts. We found that cell-cell contact exerts a strong inhibitory effect on hiPSC-CM proliferation as cell density increases. Phosphoproteomics analysis and cellular phenotyping revealed that cell-cell contact accompanies adherens junction formation, enhanced sarcomere organization, and increased contractility. Disruption of adherens junctions or sarcomere assembly via siRNA-mediated knockdown of N-cadherin or ɑ-actinin, respectively, resulted in increased cell cycle activation of hiPSC-CMs.  Furthermore, disruption of cell-cell contact enhanced nuclear translocation of β-catenin and TCF/LEF transcriptional activity that contributed to hiPSC-CM proliferation. However, this was not sufficient to drive division of hiPSC-CMs. Additional screening for putative secreted growth factors in the conditioned media from sparsely plated hiPSC-CMs revealed the enrichment of IGFBP2, which was sufficient to drive hiPSC-CM division in the presence of cell-cell contact in 3D constructs.  Conclusions: Our findings demonstrate that cell-cell contact inhibits hiPSC-CM proliferation through adherens junction formation, sarcomeric assembly, and reduced IGFBP2 secretion. Importantly, exogenous supplementation of IGFBP2 can overcome cell contact-mediated inhibition of hiPSC-CM proliferation and facilitate the growth of 3D cardiac tissue. These insights provide valuable implications for advancing cardiac tissue engineering and regenerative therapies.

overall_design: Human iPSCs (SCVI-111) were directed to differentiate into cardiomyocytes using well-established Wnt modulating protocol. Day 18 hiPSC-CMs were replated at either low (33,000 cells/cm2) or high cell density (181,000 cells/cm2), followed by a two-day culture period to allow for cellular adaptation and transcriptional stabilization. hiPSC-CMs were cultured in cardiomyocyte maintenance media (RPMI supplemented with B27+Insulin and CHI99021). On day 20, cells from both density conditions were dissociated into single-cell suspensions and loaded into the Chromium Controller (10x Genomics) for single-cell barcoded droplet generation, according to the manufacturer's protocol. Gene expression libraries were prepared using the 10x Genomics Single Cell 3' v3 chemistry kit.

first: Sean

last: Wu


title: ENO1 influences ATP pool of cytoplasm and lactate homeostasis by regulating glycolysis to promote tumor stemness and metastasis

city: Beijing

first: Xiong

address: 31 Xinjiekou East Street, Xicheng District

institute: Beijing Jishuitan Hospital

summary: This study demonstrated the role of the glycolytic enzyme alpha-enolase (ENO1) on glycolysis and stemness in gastric cancer (GC). High ENO1 expression was associated with poor prognosis and promoted malignant phenotypes and stem-like characteristics in GC. Mechanistically, ENO1 directly stimulated lactate and ATP production by regulating glycolysis, affecting lactate homeostasis and intracellular ATP pools, and co-regulating the AMPK/mTOR and PI3K/AKT signaling pathways. This ultimately drove GC stemness, epithelial-mesenchymal transition (EMT)-related markers, self-renewal, migration, and invasion.

overall_design: This submission contains RNA-Sequencing data from gastric cancer cell lines designed to investigate the transcriptional changes resulting from ENO1 (alpha-enolase) knockdown. The dataset includes three biological replicates of ENO1-knockdown cells (shENO1) and three biological replicates of control cells transfected with non-targeting shRNA (shCON).

first: Shiya

first: Ting

last: Yang

first: Xuanyu

last: Zhou

first: Gaigai

last: Shen

first: Lixin

last: Sun

first: Long

last: Yu

first: Yuanting

first: Yuliang

last: Ran


title: High-Fidelity, Efficient Human Post-Implantation Embryo Models Generated by STAT3-Induced Cell Plasticity [WGBS]

city: Guangzhou

first: Jinyi

address: No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island

institute: Guangzhou Laboratory

type: Methylation profiling by high throughput sequencing

summary: Human embryo models hold great promise as surrogates for studying development and as platforms for medicine. However, existing models lack efficiency and fidelity in replicating post-implantation stages. Here we asked if STAT3 could reprogram pluripotent stem cells (PSCs) into all blastocyst fates and generate embryo models. Using a medium for enhanced STAT3 activity (SAM), PSCs rapidly reprogram into intermediates that specify all blastocyst fates: hypoblast, trophectoderm and naïve-pluripotent epiblast, within 60 hours. Strikingly, following dissociation of SAM-treated PSCs on 60 or 120 hours and subsequent 3D assembly, structures resembling post-implantation embryos develop within 4 days, with up to 52.41±8.92% efficiency. These exhibited a bilaminar disc-like structure, including epiblast and hypoblast discs, yolk-sac and amniotic cavities, mesenchyme tissue, chorionic cavity, and trophoblast. The STAT3-mediated embryo models (stEMs) also demonstrate unparalleled molecular alignment with the Carnegie Stage 6-7 embryo reference. Thus, stEMs offer state-of-the-art models for advancing our understanding of post-implantation human embryogenesis.

overall_design: We reprogram primed hPSCs to simultaneously acquire epiblast-like, hypoblast-like and trophectoderm-like fates by exploiting STAT3 activation and TGFb inhibition. Further assembling the reprogrammed intermediates or products in 3D and cultureing the aggregates in suspension in in vitro culture medium, they self-organize into embryo like structures resembling to Carnegie Stage 6-7 human embryo.

first: Chuanxin

last: Chen

first: Xinggu

last: Wang

first: Litao

last: Chang

first: Kexin

first: Huanhuan

last: Li

first: José

last: Silva


title: PRMT5/WDR77 moonlights as an RNA-binding complex and shapes T cell function and anti-tumor immunity via post-transcriptional regulation of PDCD1

first: Shan

last: Gao

address: No. 2 Sipailou, Xuanwu District

institute: Southeast University

summary: To reveal the potential RNA targets of PRMT5 in  jurkat cells, we performed Flag Immunoprecipitation sequencing (RIP-seq) in PRMT5-Flag overexpression (OE) jurkat  cells after  stimulated with polyhydroxyalkanoates (PHA) for 48 hours.

overall_design: Jurkat cells lysate was Immunoprecipitation by Flag, then subjected to RNA-sequencing analysis

first: Yinmin

last: Gu


title: High-Fidelity, Efficient Human Post-Implantation Embryo Models Generated by STAT3-Induced Cell Plasticity [ATAC-Seq]


title: Effect of estradiol on thermoregulatory responses in ovariectomized rats administered ostruthin, a TWIK-related potassium channel agonist

city: Tokyo

first: Yuki

last: Uchida

state: Shinagawa

address: 1-5-8 Hatanodai

department: Department of Physiology

country: Japan

institute: Showa University School of Medicine

summary: This study investigated the effects of estradiol (E2) on ostruthin-induced thermoregulatory responses in ovariectomized rats, a menopausal model. Ostruthin, a component extracted from Paramignya trimera, is an agonist of cold receptors, specifically the TWIK-related potassium channels 1 (TREK1) and 2 (TREK2). Wistar rats were ovariectomized and implanted with a silastic tube with or without E2 (E2(+) and E2(−) groups). Ostruthin or vehicle was injected intraperitoneally. Body temperature (Tb), locomotor activity, tail skin temperature (Ttail), oxygen consumption, and tail-hiding behavior were measured continuously. Plasma concentrations of catecholamines, triiodothyronine, and thyroxine were measured. mRNA expression levels of TWIK-related potassium channels, transient receptor potential cation channels, E2 receptors, and selected four genes in dorsal root ganglia were assessed. For the electrophysiological study, ventral root reflex responses induced by dorsal root stimulation were measured in in vitro preparations of neonatal rat spinal cord applied 500 μM ostruthin. Ostruthin increased Tb in the E2(+) group. In ostruthin-treated groups, Tb in the E2(+) group was greater than that in the E2(−) group. Ostruthin decreased Ttail. There was a tendency for E2 to decrease Ttail. E2 increased plasma triiodothyronine. E2 increased TREK1, nerve growth factor-inducible, and nitric oxide synthase 1 mRNA level. No significant differences in other measurements were observed among the groups. The excitation of sensory nerves by ostruthin and the increase of TREK1 by E2 may facilitate cold sensitivity. Ostruthin and E2 suppressed heat dissipation by tail skin vasomotor control. E2 may increase Tb in a menopausal model, potentially through modulation of TREK1.

overall_design: To investigate the effects of estradiol (E2) on ostruthin-induced thermoregulatory responses in ovariectomized rats, the dorsal root ganglia in rats were analyzed by RNA-seq.

first: Shotaro

last: Kamijo

last: Samejima

first: Hiroshi

last: Onimaru

first: Masahiro

last: Hosonuma

first: Hikaru

last: Isobe

first: Keiko

last: Ikeda

first: Motoyasu

last: Honma

first: Yuri

last: Masaoka

first: Masahiko

last: Izumizaki


title: Bulk RNA-seq of MDA-MB-231 cells under dasatinib treatment

city: Taipa

first: feng

last: yu

address: Avenida de Universidade

country: Macau

institute: University of Macau

summary: Triple-negative breast cancer (TNBC) is characterized by high metastatic potential and poor prognosis, underscoring the urgent need for effective therapeutic strategies.  Dasatinib emerged as a promising anti-metastatic agent in TNBC.To elucidate the molecular mechanisms by which dasatinib inhibits breast cancer progression, we conducted bulk RNA sequencing (RNA-seq) on MDA-MB-231 cells treated for 6, 12, 24, and 48 hours.

overall_design: Transcriptomic analysis of MDA-MB-231 cells following dasatinib 0,6,12,24,48 hours-treatment.

first: Xinyu

last: Guo

first: Heng

last: Sun

first: Feng

last: Yu

first: Rong

last: Zhou

first: Chu-xia

last: Deng


title: ChIP-seq to measure binding of NIPBL/MAU2, RAD21, and CTCF in mouse embryonic stem cells and neural progenitor cells

city: San Francisco

first: Elphege

last: Nora

address: 555 Mission Bay Blvd S

department: CVRI

institute: UCSF

summary: Mammalian chromosomes are folded by the cohesin complex, which creates chromatin loops that are extruded as cohesin translocates along the chromatin fiber. This dynamic process regulates gene expression by controlling the frequency of contacts between enhancers and promoters. We analyzed where in the genome loop extrusion occurs to discover where extrusion initiates and whether particular regions are extruded more than others. We measured NIPBL/MAU2 binding in mouse embryonic stem cells and neural progenitor cells, and found that NIPBL/MAU2 is enriched at enhancers compared to promoters. We used the amount of cohesin binding at CTCF sites as a readout of cohesin traffic, and found that the NIPBL/MAU2 binding sites only modestly boost nearby cohesin levels.

overall_design: We measured NIPBL and MAU2 binding by performing spike-in calibrated HA ChIP-seq in cell lines in which NIPBL or MAU2 was tagged with an HA epitope and FKBP degron. Cells treated with dTAG for 24 hours to deplete NIPBL or MAU2 and untagged cell lines are used as negative controls. We also measured RAD21 and CTCF binding with endogenous antibodies. We used mouse embryonic stem cells and neural progenitor cells.

first: Erika

last: Anderson

first: Rini

last: Shah

first: Karissa

last: Hansen


title: Bulk RNA sequencing SCA1+ fibroblasts from murine skin in the uninjured state and 16 hours, 1.5 days, and 3 days post-wounding

city: Washington

first: Brett

middle: Adam

last: Shook

state: DC

address: 2300 I St NW

department: Biochemistry & Molecular Medicine

institute: George Washington University

summary: Fibroblasts are emerging as potent modulators of wound-induced inflammation in the skin. We have observed that fibroblasts expressing the surface marker SCA1 are enriched for expression of proinflammatory factors after injury. To characterize how the expression profile of these cells changes as inflammation initiates and resolves following injury, we performed bulk RNA sequencing of isolated SCA1+ fibroblasts from mouse skin in the uninjured state and multiple time points during the post-injury inflammatory phase.

overall_design: Male C57BL/6 mice were used to generate all samples. Unwounded back skin was harvested from three mice for nonwounded (NW) samples 1-3. Full-thickness excisional wounds were made on the back skin of mice using a 4mm biopsy punch and wounds were harvested 16 hours post-wound (hpw), 1.5 days post-wound (dpw), and 3dpw (3 mice per time point). Cells from wound samples and uninjured back skin were isolated with tissue mincing and a liberase digestion solution. Following isolation of the SCA1+ fibroblasts, RNA was extracted from cells and used for sequencing library generation.

first: Veronica

last: Amuso

first: MaryEllen

last: Haas

first: Anelia

last: Horvath


title: Gnai1+ stromal cells regulate intestinal goblet and Paneth cell differentiation through c-Jun signaling

first: Ye-guang

last: Chen

address: Tsinghua Road, Medical Building

department: School of life science

institute: Tsinghua University

summary: Combining single-cell and spatial transcriptomics for mapping different intestinal segments is still relatively absented, and the subtypes of intestinal stromal cells and their downstream signling also remain obscure. Our study provides a comprehensive view of 18 identified cell types across five mouse intestinal segments using single-cell RNA sequencing (scRNA-seq). Integrating scRNA-seq with spatial transcriptomics reveals gene profiles along both segmental and crypt-villus spatial dimensions, including cell characteristics, interactions, signaling networks, extracellular matrix contributions, and functional coordination. Not only the different subtypes of intestinal immune cells were analyzed, but also a subtype of Pdgfra-high stromal cells, Gnai1+ stromal cells, was identified. These cells can support intestinal morphology and regulate the activities of goblet cells, Paneth cells, and intestinal stem cells via the activation of c-Jun and Wnt signaling. Thus, we have compiled a publicly available single-cell and spatial transcriptomics resource covering five intestinal segments to facilitate further research, particularly on stromal cell populations and intestinal microenvironment homeostasis.

overall_design: Single-cell RNA sequencing libraries were constructed to profile cellular heterogeneity and gene expression across the duodenum, jejunum, ileum, colon, and rectum segments of the mouse intestine

first: Yalong

last: Wang

first: Wanlu

last: Song


title: High-Fidelity, Efficient Human Post-Implantation Embryo Models Generated by STAT3-Induced Cell Plasticity

first: Jinyi

last: Wu

overall_design: Refer to individual Series


title: High-Fidelity, Efficient Human Post-Implantation Embryo Models Generated by STAT3-Induced Cell Plasticity [Bulk RNA-seq]

first: Chuanxin

first: Xinggu

first: Litao

last: Chang

first: Kexin

first: Huanhuan

last: Li

first: José

last: Silva


title: Myogenic effects of butyrate and pentanoate on C2C12 cells

city: Shanghai

first: Ziyi

last: Cao

address: No. 221, Yan'an West Road, Jing'ansi Street, Jing'an District, Shanghai

institute: Huadong hospital affiliated to Fudan University

summary:
In order to study the effects of butyrate and pentanoate on the proliferation of muscle cells, we established C2C12 cell lines and intervened C2C12 cells with butyrate and pentanoate respectively.
We then performed gene expression profiling analysis using data obtained from RNA-seq of thses three groups.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for C2C12 cells, butyrate-treated C2C12 cells and pentanoate-treated C2C12 cells

first: Li

last: Guan


title: Butyl benzyl phthalate as a key component of phthalate ester in relation to cognitive impairment in NHANES elderly individuals and experimental mice

city: NanJing

first: Yongquan

last: Yu

state: JiangSu

address: 87 Dingjiaqiao, Gulou District

department: College of Public Health

summary: Phthalates are a group of neurotoxicants with cognitive-disrupting potentials. Given the structural diversity of phthalates, the corresponding neurotoxicity is dramatically altered. To identify the potential contributions of different phthalates on the process of cognitive impairment, data of 836 elders from the NHANES 2011-2014 cycles were used. Survey-weighted logistic regression and principal component analysis-weighted quantile sum regression (PCA-WQSR) models were applied to estimate the independent and combined associations of 11 urinary phthalate metabolites with cognitive deficit [assessed by 4 tests: Immediate Recall (IR), Delayed Recall (DR), Animal Fluency (AF), and Digit Symbol Substitution test (DSST] and to identify the potential phthalate with high weight. Laboratory mice were further used to examine the effect of phthalates on cognitive function and to explore the potential mechanisms. In logistic regression models, MBzP was the only metabolite positively correlated with four tests, with ORs of 2.53 [quartile 3 (Q3)], 2.26 (Q3), 2.89 (Q4) and 2.45 (Q2), 2.82 (Q4) for IR, DR, AF and DSST respectively. In PCA-WQSR co-exposure models, low-molecular-weight (LMW) phthalates were the only PC positively linked to DSST deficit (OR: 1.93), which was further validated in WQSR analysis (WQS OR7-phthalates: 1.56 and WQS OR8-phthalates: 1.55); consistent with the results of logistic regression, MBzP was the dominant phthalate. In mice, butyl benzyl phthalate (BBP), the parent phthalate of MBzP, dose-dependently reduced cognitive function and disrupted hippocampal neurons. Additionally, the hippocampal transcriptome analysis identified 431 differential expression genes, among which most were involved in inhibiting the neuroactive ligand‒receptor interaction pathway and activating the cytokine‒cytokine receptor interaction pathway. Our study indicates the critical role of BBP in the association of phthalates and cognitive deficits among elderly individuals, which might be speculated that BBP could disrupt hippocampal neurons, activate neuroinflammation and inhibit neuroactive receptors. Our findings provide new insight into the cognitive-disrupting potential of BBP.

overall_design: The hippocampal samples (N=3 replicates, 4 months old) from 50 mg/kg/day BBP treated C57BL/6 mice and control C57BL/6 mice (N=3 replicates, 4 months old) were used for  transcriptome analysis

first: Yucheng

first: Yu

last: Dong

first: Shuge

last: Shu


title: The impact of the Sprtn mutation on gene expression in liver tissue

city: Split

first: Maria

last: Boskovic

address: Soltanska 2A

department: Laboratory for Cancer Research

country: Croatia

institute: University of Split School of Medicine

summary:
Biallelic mutations in the SPRTN gene cause an autosomal recessive progeroid disease known as Ruijs–Aalfs syndrome. Patients with Ruijs–Aalfs syndrome display symptoms of premature ageing and typically develop hepatocellular carcinoma during adolescence. To study the functional role of this protein, we generated knock-in mice (Sprtn Y118C/Y118C) that largely recapitulate the Ruijs–Aalfs phenotype. These mice harbour the equivalent of the Y117C missense mutation described in Ruijs–Aalfs patients.

SPRTN has recently been implicated in DNA repair, specifically in the resolution of DNA–protein crosslinks (DPCs), which facilitates replisome bypass and allows translesion synthesis across DPC adducts. Understanding this DNA repair pathway is of paramount importance, as cells lacking SPRTN are not viable, and DNA–protein lesions can be induced by UV light, ionizing radiation, or normal cellular metabolism. Moreover, a broad spectrum of chemotherapeutic drugs induces protein–DNA crosslinking.

In our study, we compared the bulk transcriptome of Sprtn Y118C/Y118C and wild-type mice using RNA extracted from liver tissue.

overall_design: Gene expression was analysed in male C57BL/6J Sprtn Y118C/Y118C and wild-type mouse liver.

first: Janoš

last: Terzić

last: Bošković


title: High-Fidelity, Efficient Human Post-Implantation Embryo Models Generated by STAT3-Induced Cell Plasticity [scRNA-Seq]


title: Transcriptome profiles of BEZ235 treated Ewing Sarcoma cells

city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

country: France

institute: GenoSplice technology

overall_design: TC71 cells treated with either the PI3K/mTOR inhibitor BEZ235 or DMSO

first: M

last: Paronetto

first: R

last: Palombo


title: Identification of SLC7A1 as a potential therapeutic target for high-grade meningioma

first: lairong

last: song

state: 北京

address: South Fourth Ring West Road 119, Fengtai District

institute: Beijing Tiantan hospital

summary: High-grade meningioma remains a therapeutic challenge to medical oncologists. It is urgent to uncover novel molecular targets. Solute carrier family 7 member 1 (SLC7A1) was highly expressed in high-grade meningioma and associated with poor prognosis of patients. SLC7A1 knockdown significantly inhibited the proliferation and invasion of malignant meningioma cells. In addition, the small-molecule drug AZ628 showed an excellent antiproliferative effect on malignant meningioma cells, indicating that it is a potential antitumor drug for high-grade meningioma. Our study revealed the essential roles of SLC7A1 in the malignant progression of meningioma, suggesting SLC7A1 as a potential antitumor target for high-grade meningioma.

overall_design: In order to verify the molecular function of SLC7A1 in meningioma cells, we knocked down the expression of SLC7A1 in two meningioma cell lines and performed RNA sequencing. Additionally, to explore the anti-tumor mechanism of AZ628, we treated two meningioma cell lines with AZ628 and conducted RNA sequencing.

first: Lairong


title: Maternal Probiotic Supplementation Effects on the Placenta-Brain Axis

status: Public on Sep 26 2025

city: Columbia

first: Trupti

last: Joshi

state: Missouri

address: 103 Math Science Building

department: Department of Biomedical Informatics, Biostatistics and Medical Epidemiology (BBME)

institute: University of Missouri-Columbia

summary: The rate of probiotic usage by pregnant women in the US and Canada ranges from 1.3 to 3.6 %. Probiotic supplements are available without a prescription and have gained currency in treating a variety of ailment ranging from reducing risk of constipation, diarrhea, other gastrointestinal conditions, eczema, pre-term birth, and prevent adverse pregnancy outcomes, including gestational diabetes mellitus (GDM) and depression/anxiety. Three possible mechanisms by which maternal probiotic supplementation might influence the placenta are through 1) directly impacting possible bacteria residing in the placenta (placenta microbiome), 2) altering bacterial metabolites produced by gut microbiota within the mother that induce placental changes, and 3) maternal probiotics might affect the composition of the bacteria within the maternal gut that affects her immune cells and their responses to the heterologous placenta. For the second potential mechanism, bacterial metabolites that might influence placenta include short chain fatty acids (SCFAs), polyamines (PAs), and Vitamins B9 (Folic Acid) and 12 (Cobalamin), among others. This project aims to determine the effects maternal probiotic supplementation in mice might have on the fetal placenta. With the number of women taking over probiotic supplements increasing, further research is needed to determine how these bioactive agents may affect the placenta and health of the offspring.

overall_design: RNA-seq profiling of wildtype mouse placenta and fetal brain from control mouse dams and mouse dams exposed to probiotic supplementation before and during pregnancy.

first: Rosalind

middle: T

last: Herrington

first: Zhen

last: Lyu

first: David

last: Ellenberger

first: Sarah

middle: E

last: Seda

first: Cheryl

last: Rosenfeld


title: Biomimetic Strategy Driven Deubiquitination for Enhanced Ferroptosis and Cancer Immunotherapy

first: Mingyang

last: Li

state: --- Select One ---

address: 324 Jingwu Road, Jinan 250021, China

institute: Shandong Provincial Hospital Affiliated to Shandong First Medical University

summary: Ubiquitination is the key mechanism that mediates protein stability and degradation, and the interference of ubiquitination is a promising approach to improve the therapeutic effects in cancer therapy. Here, we demonstrate that targeting inhibition of deubiquitinase OTUB1 could increase the ubiquitylation of PD-L1 and GPX4, which makes tumor cells vulnerable to the ferroptosis and immunotherapy. The therapeutic vehicles are designed through the encapsulation of metal-polyphenol network nanocomplexes (GA/Fe), doxorubicin (DOX), and siRNA targeting OTUB1 (siOTUB1) within a modified tumor cell membrane (SFD@M). Targeting delivery of SFD@M driven by tumor membrane efficiently decreases the expression of PD-L1 and GPX4 in tumor tissues. Without the protection of GPX4, GA/Fe complexes in SFD@M induce strong ferroptosis in tumor cells and initiate anti-tumor immune responses. Low expression of PD-L1 in tumor tissues due to excess ubiquitination maintain the activation of CD8+ T cells. In addition, the overexpression of PD-1 on edited tumor cell membrane regulates the function of Tregs and MDSCs, and further enhanced the anti-tumor effect of CD8+ T cells. SFD@M demonstrates efficient inhibition of tumor growth in orthotopic tumor models and cell line-derived xenograft (CDX) models in humanized NOG mice. This study employs the ubiquitination process in tumor cells to develop a biomimetic strategy that enhances ferroptosis and augments the immunotherapeutic efficacy in cancer treatment.

overall_design: 1.OTUB1 knockdown LLCs as well as its negative control were obtained through transfected with lenti-virus, which were further used to construct murine lung cancer orthotopic models, and RNAseq was performed to analyze the DEGs between OTUB1 knockdown murine lung cancer tissues and its negative control. 2.In order to gain a deeper understanding of the mechanism of SFD@M in cancer treatment. The mice were divided into blank group and SFD@M group. RNAseq was performed to investigate the changes in gene expression between the tumor tissues from Blank group and SFD@M group.

first: Wenli

last: Ning

first: Ziqi

last: Zhang

first: Siyu

last: Xie

first: Linhan

last: Ding

first: Junhao

last: Liang

first: Dongsheng

first: Jiwei

last: Cui

first: Hauwei

last: Wu

first: Xiao

last: Fu


title: Temporal RNA-seq atlas of breast muscle development in purebred and crossbred broilers

first: Qiang

last: Huang

address: No. 2 Yuanmingyuan West Road, Haidian District, Beijing

institute: China Agricultural University

summary: A total of 460.76 Gb of high-quality bulk RNA-Seq data were generated from six biological replicates per group at each time point. This dataset can be used to study molecular networks during muscle development, and serves as a reference model for comparative analyses of growth heterosis in animals.

overall_design: We sequenced 72 breast muscle samples collected at embryonic day 17 and post-hatching days 1, 21, and 42 across Cornish purebred, White Plymouth Rock purebred, and their crossbred progeny.

first: Huang

last: Qiang

first: Shuang

last: Gu

first: Yuchen

last: Jie

first: Ning

last: Yang

first: Chaoliang

last: Wen


title: Tissue resident memory T cells populate the human uveal tract

city: Oxford

first: Andrew

last: Foers

address: Roosevelt Dr

country: United Kingdom

institute: Kennedy Institute of Rheumatology

summary: The current concept is that the eye is an immune privileged site endowed with innate immune regulatory networks to maintain organ function. We now have evidence that resident T cells occupy intraocular tissues. In immune-mediated inflammatory diseases, such as psoriasis and rheumatoid arthritis, tissue resident T cells trigger disease flares in the skin and joints. This suggests resident T cells in the uvea may have similar functions in non-infectious immune-mediated uveitis, a collective term for autoinflammatory and autoimmune diseases of the uveal tract causing intraocular inflammation.  Here, we demonstrate by spectral cytometry and immunofluorescence imaging that non-inflamed uveal tissue contains multiple T cell subtypes including CD8+ CD103+ tissue resident memory T (TRM) cells. Using single cell RNA & T cell receptor (TCR) sequencing to profile aqueous humour cells from donors with acute, active uveitis, we identify clonally expanded T cells which are enriched for TRM -associated genes. We further show that in donors with active uveitis, CD8+ CD103+ T cells persist within tissue in the uveal tract. Using bulk RNA sequencing and weighted gene co-expression network analysis (WGCNA) we show that quiescent iris tissue from donors with a history of uveitis are enriched for genes associated with T cell activation and antigen presentation. Finally, we demonstrate that TRM cells persist in the anterior uvea in mice following resolution of experimental autoimmune uveoretinitis (EAU). Our results show that the human eye contains T cells both in health and during active inflammation. Our findings challenge the dogma that the eye is devoid of lymphocytes and supports the concept of resident T cell involvement in the pathogenesis of non-infectious immune-mediated uveitis and as promising targets for therapy.

overall_design: Aqueous humour from consenting patients was collected from pateints with anterior uveitis. Cells were then analysed by scRNA-seq.

middle: D

first: Srilakshmi

last: Sharma


title: Integrated transcriptomic analysis revealed lymphatic-mediated immune dynamics after myocardial infarction

city: 深圳

first: Xueting

last: Chen

address: 广东省深圳市盐田区华大公寓

institute: University of Chinese Academy of Sciences

summary: Cardiac lymphatic vessels actively regulate immune responses after injury. Intercellular cell adhesion molecule-1 (ICAM-1), a cell surface glycoprotein, extensively expresses in endothelial cells and participates in inflammatory processes by regulating leukocyte recruitment from circulation. However, the specific role of lymphatic endothelial cells (LECs) Icam1 in regulating the immune microenvironment associated with myocardial infarction (MI) remains elusive. In this study, we generated an LEC-specific Icam1 conditional knockout (cko) model and performed single-cell RNA sequencing to evaluate the cellular dynamic features at 3-, 7-, 21-, and 42- days post-MI. Our results showed that Icam1 deletion increased inflammation and fibrosis, indicating aggravated cardiac damage. Our findings indicate that LEC Icam1 might be a potential therapeutic target for improving post-MI outcomes.

overall_design: We generated lymphatic-specific Icam1 conditional knockout (Icam1cko) model by crossing Icam1flox/flox with Prox1CreERT2 mice, and induced recombination by tamoxifen administration one week prior to MI. The cardiac tissue at 3-, 7-, 21-, and 42-days post-MI (dpMI) were harvested, and cell suspension was stained with PE Rat anti mouse CD31 (BD Pharmingen, 553373) or APC Rat anti mouse CD45 (BD Pharmingen, 559864), then followed incubated with anti-PE microbeads (MACS,130-105-639) or Anti-APC microbeads (MACS,130-090-855). Single cells from CD31+ or CD45+ cell populations were collected by FACS sorting for further analysis using single-cell RNA sequencing.

first: Zhao


title: C1QBP forms a positive feedback loop with the PAICS/FAK/c-Myc axis to promote cholangiocarcinoma proliferation

city: changsha

first: ruijiang

last: Zeng

address: No.139 Renmin Road Central

institute: The Second Xiangya Hospital of Central South University

summary: Cholangiocarcinoma (CCA) is a highly lethal malignancy with increasing incidence and mortality rates worldwide. To investigate the mechanisms underlying CCA tumorigenesis, we conducted bioinformatics analysis, which revealed that C1QBP is the most upregulated membrane protein in CCA and is involved in energy metabolism, nucleotide repair, and resistance to platinum-based chemotherapeutic agents in CCA. Our findings revealed that C1QBP is significantly overexpressed in CCA and is strongly associated with increased proliferation and poor prognosis. Mechanistic studies further demonstrated that c-MYC can upregulate C1QBP expression at the transcriptional level, subsequently influencing PAICS/FAK expression and promoting CCA growth. Interestingly, C1QBP also regulates c-MYC expression by increasing FAK phosphorylation, establishing a positive feedback loop that drives tumor progression. Additionally, we developed a novel siRNA delivery system, si@LH, by encapsulating siC1QBP within hyaluronic acid-dopamine hydrogel-coated liposomes. Ex vivo experiments confirmed that this system enables prolonged and stable C1QBP inhibition. In conclusion, our study suggests that C1QBP may serve as a valuable biomarker for cholangiocarcinoma prognosis and that silencing C1QBP with si@LH, either alone or in combination with other targeted or immunotherapies, holds promise as a therapeutic strategy for cholangiocarcinoma.

overall_design: Sequencing analysis of the role of C1QBP in cholangiocarcinoma cells


title: OSR1 and SIX2 Drive Divergent Transcriptional Programs in Human Kidney Cells: Implications for Regeneration and Tumorigenesis\

city: TEL AVIV

first: Naomi

last: Pode-Shakked

address: Weizmann St 6

department: Pediatric Nephrology

country: Israel

institute: Tel Aviv Souraski Medical Center

summary: During human nephrogenesis, nephron progenitor cells generate approximately one million nephrons. We investigated the effects of ectopic expression of OSR1 and SIX2, both individually and in combination, in adult human kidney cells. OSR1 and SIX2 induced distinct reprogramming programs with differential functional outcomes. SIX2 overexpression maintained epithelial morphology while significantly enhancing proliferation and clonogenic efficiency. Transcriptionally, SIX2 established epithelialization and cell cycle networks, downregulating proximal tubule markers, while upregulating distal nephron markers and proliferation genes. In vivo, SIX2-expressing cells formed organized tubular structures with distinct luminal architecture. In contrast, OSR1 overexpression induced morphological changes and activated developmental morphogenetic pathways but did not enhance proliferation and showed minimal tubulogenic capacity. RNA sequencing analysis revealed coordinated changes in nephron segment-specific markers and activation of distinct transcriptional programs.\

overall_design:
Expression profiling by high-throughput RNA sequencing. Adult human kidney epithelial cells (hKEpCs) were transduced with lentiviral vectors encoding SIX2, OSR1, OSR1+SIX2, or mCherry control. Three biological replicates per condition (except Double condition with 2 replicates). RNA extracted using RNeasy Mini Kit, libraries prepared with TruSeq Stranded mRNA Library Prep Kit, sequenced on Illumina NovaSeq 6000 (paired-end 150bp, >30M reads/sample). Differential expression analyzed with DESeq2.\

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first: Osnat

last: Cohen-Zontag

first: Dorit

last: Omer

first: Orit

last: Harari-Steinberg

first: Einav

last: Vax

first: Oren

last: Pleniceanu

first: Benjamin

last: Dekel


title: TRPV1-Independent and Sex-Specific Capsaicin Signatures in Drosophila

city: Institute

first: Gerardo

last: Flores-Iga

state: West Virginia

address: Integrated Research and Extension Building

department: Biology

institute: West Virginia State University

summary: In mammals, capsaicin activates the transient receptor potential vanilloid 1 (TRPV1) channel to induce pungency, but its effects in species lacking TRPV1 remain unclear. In Drosophila melanogaster, which has no TRPV1 ortholog, capsaicin triggers proboscis reflexes, drives attraction, and shapes feeding and locomotion in a sex- specific manner. Females exhibit delayed habituation and increased sleep fragmentation, whereas both sexes reduce evening locomotion. Single-nucleus RNA sequencing (snRNA-seq) revealed broader transcriptional responses in females, including modulation of peptidergic neurons and circadian-linked glial clusters. Cell–cell communication analyses identified a female-biased TGF-β and AstA signaling axis in learning and memory centers, contrasting with male-enriched WNT, NPF, and Dh31 pathways. These results uncover TRPV1-independent mechanisms through which capsaicin influences neural circuits, highlighting sex-specific strategies for integrating sensory cues and providing a framework to explore the ecological and evolutionary significance of capsaicin sensitivity beyond nociception.

overall_design: We collected brain samples from flies exposed to control and capsaicin diets to perform snRNA-seq. Female and male flies were collected during ZT6–12.

first: Mohankumar

last: Amirthalingam

first: Carlos

last: Lopez-Ortiz

first: Rima

last: Saha

first: Elizabeth

last: Brown

first: Padma

last: Nimmakayala

first: Umesh

middle: K

last: Reddy


title: Iron-sensitive RNA regulation by poly C binding proteins [RIP-Seq]

city: Chapel Hill

first: Maria

last: Aleman

state: NC

address: 120 Mason Farm Rd.

institute: University of North Carolina at Chapel Hill

summary: Iron is important for normal cellular function and posttranscriptional mechanisms regulate the cellular response to iron deficiency. In this study we explore how RNA binding proteins, PCBP1 and PCBP2, exhibit iron-sensitive RNA regulation.

overall_design: K562 cells were induced (with doxycycline) to expressed either a Flag-tagged PCBP1, wildtype (WT), a non-iron binding mutant (∆Fe), a non-RNA binding mutant (∆RNA), or Flag-tagged-GFP. Cells  were then treated overnight with DMSO (control) or 10 µM iron chelator (21H7). With two biological replicates, cells were subjected to formaldehyde crosslinking and immunoprecipitation using anti-Flag antibodies. Bound RNA was isolated and sequenced along side inputs.

first: Aleman

last: Maria

first: Dominguez

last: Daniel


title: Iron-sensitive RNA regulation by poly C binding proteins [DKD_RNASeq]

overall_design: K562 cells were treated with DMSO or 10 µM iron chelator 21H7 after being transduced to express short hairpin RNAs targeting luciferase (shCtrl) or PCBP1 (shPCBP1) and PCBP2 (shPCBP2).

first: Daniel

last: Dominguez


title: Regional Conservation and Transcriptional Regulation of  Tumor-Associated Genes by macroH2A1 Deposition in  Mammalian Cells

city: Minhang

first: deng

last: yongzhuo

state: Shanghai

address: DongchuanoRoad N0.800

institute: Shanghai Jiao Tong University

summary: Histone variant macroH2A1 has been widely recognized as a suppressor of gene expression. Recently, a cell cycle dependent deposition of macroH2A1 is discovered in mouse cells, but whether this process exists in human chromatin is unclear, which might be crutial for related diseases, particularly cancer. In this study, we firstly demonstrate that dynamic macroH2A1 domains occurs in both normal and cancerous human cells. Our findings provide new epigenetic insights into the role of macroH2A1 in malignant proliferation, offering a novel perspective for furture cancer research.

overall_design: native Chromatin immunoprecipitation and DNA-sequencing (nChIP-seq) for histone variants macroH2A1 in ARPE-19 cells and HeLa cells in G1/S phase and metaphase

first: Yongzhuo

last: Deng

first: Zeqian

last: Xu

first: Xinhui

last: Li

first: Le

last: Zhang

first: Zhifeng

last: Shao

first: Bishan

last: Ye


title: WDR4 Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression via eIF4E-Mediated mRNA Translation

city: Wuhan

first: Minghe

state: Hubei

address: Donghu Road

institute: WuHan University

summary: Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment of hepatocellular carcinoma (HCC), profoundly influencing disease progression and clinical outcomes. WDR4, a tRNA-binding scaffold protein involved in N⁷-methylguanosine (m⁷G) methylation, remains poorly characterized in terms of its independent biological functions. Here, we report that WDR4 is markedly upregulated in HCC-infiltrating TAMs and correlates with poor patient prognosis. Using HCC tumorigenesis models, we demonstrate that selective deletion of Wdr4 in monocyte-derived macrophages—but not in Kupffer cells—drives TAM polarization toward an anti-tumor phenotype, thereby restraining HCC progression. Mechanistically, cytoplasmic WDR4 exerts a non-m⁷G-dependent role in promoting translation by directly interacting with eIF4E2. This interaction selectively enhances eIF4E-mediated translation of ABCA1, facilitating cholesterol efflux and consequently promoting tumor progression. For translational application, we developed a CpG-conjugated siRNA delivery system that specifically targets Wdr4 in TAMs, reprogramming the microenvironment toward a tumor-suppressive state and inhibiting tumor growth. Notably, this strategy, when combined with PD-1 blockade, elicits durable anti-tumor immune responses. Overall, the WDR4/eIF4E2/ABCA1 axis regulates TAM polarization and drives HCC progression, offering a promising therapeutic target for enhancing the efficacy of HCC immunotherapy.

overall_design: An orthotopic HCC model was established in Wdr4^f/f and Wdr4^f/f Lyz2-Cre(Wdr4^cKO) mice using Hepa1-6 cells.  Tumour tissues were harvested, and CD45+ immune cells were isolated for scRNA-sequencing transcriptome analysis.

first: Jie

last: Liu

first: Peng

last: Xia

first: Yufeng

last: Yuan


title: E2F1 induces a G0-G1 re-entry transcriptional program without changing chromatin accessibility [ATAC-seq]

city: Santa Cruz

first: Ali

last: Shariati

address: 1156 High St

department: Biomolecular Engineering

institute: University of California Santa Cruz

summary: Many cells in our body reside in a reversible nondividing state termed G0 or quiescence. Precise regulation of entry and exit from G0 is critical for maintaining tissue homeostasis. G0 entry can occur when cells do not receive the required signals for cell cycle progression, leading to active repression of cell cycle genes through several mechanisms, including formation of repressor complexes to restrict chromatin accessibility for transcriptional activators. G0 cells can re-enter the G1 phase of the cell cycle upon receiving growth factor signals, resulting in activation of the Mitogen-Activated Protein Kinase pathway, converging on E2F transcription factors. Ectopic expression of E2F1 alone, a transcriptional activator, is sufficient to promote G0 exit without requiring the upstream signals, but it is unclear how E2F1 can overcome the chromatin lockdown in G0 cells to activate cell cycle genes. To better understand this mechanism, we compared dynamics, gene regulation and chromatin accessibility state between E2F1-mediated and growth factor (serum)-induced cell cycle reentry. Using live cell single cell tracking, we observe that E2F1 induction leads to accelerated cell cycle progression compared to regular serum-induced cell cycle re-entry. This accelerated cell cycle re-entry by E2F1 is accompanied by faster upregulation of cell cycle genes. Interestingly, we find that E2F1 preferentially binds to gene promoters that remain in a poised chromatin state after G0 induction, suggesting that G0 cells are prepared for cell cycle re-entry via regulating chromatin states in essential cell cycle genes.

overall_design: Constucts for doxycycline inducible expression of E2F1 or empty-vector (EV) control were stably integrated into 3T3 cells. The E2F1 and EV 3T3 cells were serum starved for 48 hours to induce a G0-like state, followed by E2F1 induction, EV induction or 10% serum addition, to induce G1/S phase reentry. Samples were collected at 0, 2, 6 and 12 hours after induction or serum addition. RNA was extracted for RNA-sequencing and nuclei were extracted for ATAC-Seq. In addition, cells were prepared for E2F1 ChIP-Seq at the 12 hour time point only. Together the RNA-Seq, ATAC-Seq and ChIP-Seq were used to identify E2F1 gene regulatory network involved in cell cycle reentry from G0.

first: Gerrald

middle: A

last: Lodewijk

first: Benjamin

last: Topacio

first: Silvart

last: Arabian

first: Seungho

last: Lee

first: Abolfazl

last: Zargari

first: Znala

last: Williams

first: Edward

last: Wu

first: Sayaka

last: Kozuki

first: Rana

last: Rahimi

first: Neda

last: Bidoki

first: Vanessa

last: Jonsson

first: Eric

last: Malekos

first: Susan

last: Carpenter

first: Gerd

last: Muller

first: Seth

last: Rubin


title: E2F1 induces a G0-G1 re-entry transcriptional program without changing chromatin accessibility [ChIP-seq]


title: ID2 downregulation promotes tumor cell proliferation via elevated TCF3 activity in Multiple Myeloma [ATAC-seq]

city: Boston

first: Mehmet

middle: Kemal

last: Samur

state: MA

address: 450 Brookline Ave

institute: Dana Farber Cancer Institute

summary: Multiple myeloma (MM) is characterized by rewired transcriptional circuits. Transcription factors and their cofactors are major and selective non-oncogene dependencies in MM cells. By performing a gain-of-function (GOF) perturbation screen in MM cell lines, we identified the Inhibitor of DNA binding (ID) proteins as putative suppressors of MM cell fitness. Among the ID genes, ID2 was found to be downregulated in MM patient cells and acted as a tumor suppressor by directly binding and repressing the transcription factor TCF3. Lower ID2 expression in MM cells conferred a proliferative advantage by allowing higher TCF3 activity in tumor cells, resulting in a striking dependency on this TF. To the contrary, ID2 overexpression reduced TCF3 binding to DNA and rewired the MM transcriptome, leading to cell-cycle arrest and senescence. The myeloma bone marrow milieu participates in this process by further decreasing the expression of ID2 and enhancing TCF3 activity, revealing a novel mechanism by which the tumor microenvironment controls MM cell behavior.

overall_design: ATAC-seq was performed on KMS20 transfected either with control or ID2-expressing doxycycline-inducible vector after 24 hours of incubation with 0.25 µg/ml doxycycline.

first: Mariateresa

last: Fulciniti

first: Yao

last: Yao

first: Tommaso

last: Perini

first: Charles

last: Epstein

first: Moritz

last: Binder

first: Nikhil

middle: C

last: Munshi


title: Suture-specific regulation of coronal and lambdoid suture patency by PTHLH and HHIP activity in mice

city: New York

first: Harm

middle: van

last: Bakel

state: New York

address: One Gustave L. Levy Place, Box 1498

department: Genetics and Genomic Sciences

institute: Mount Sinai School of Medicine

summary: Craniofacial development depends on the formation of fibrous joints, or sutures, between skull bones. Premature fusion of sutures, or craniosynostosis, is a common human pathology. Ectopic Hedgehog (HH) signaling is one cause of craniosynostosis. Hhip encodes an inhibitor of HH ligands, and we previously identified coronal suture dysgenesis in embryonic Hhip-/- mice, in which suture mesenchyme was depleted between closely opposed but unfused osteogenic fronts at E18.5. Here, we report that the lambdoid suture fuses in Hhip-/- mice by E18.5. RNA-seq analysis of the Hhip-/- coronal and lambdoid sutures show that HH target gene expression, including Pthlh, is upregulated. Paradoxically, expression of Ihh is downregulated. We hypothesized that PTHLH, a negative regulator of Ihh expression, may reduce HH signaling to promote coronal suture patency and prevent fusion of the Hhip-/- coronal suture. We generated Hhip-/-;Pthlh-/- embryos and found that coronal sutures are fusing by E18.5. Our results reveal a previously undescribed role for Pthlh in suture development and demonstrate suture-specific roles for HH inhibitors in maintaining suture patency.

overall_design: To comprehensively identify and compare the transcriptional consequences of loss of Hhip within coronal and lambdoid sutures, we performed RNA-seq analysis of Hhip-/- and WT sutures at E18.5 in a murine C57BL/6, Swiss-Webster, 129 background. Up to four mice were used in each group.

first: Madrikha

last: Saturne

last: Motch Perrine

first: Qingyang

last: Li

first: Joan

last: Richtsmeier

first: Ethylin

middle: W

last: Jabs

last: van Bakel

first: Greg

last: Holmes