title: RNAPII and DNA supercoiling regulate cohesin engagement in neurons [RNA-Seq]

status: Public on Nov 01 2025

city: Dallas

first: Ram

last: Madabhushi

address: 5323 Harry Hines Blvd

institute: UT Southwestern Medical Center

summary: Chromatin looping by CTCF and cohesin is thought to be crucial for chromosome organization and gene transcription. Yet the precise relationships between CTCF, cohesin, and transcription in neurons are still poorly understood. To address this issue, we compared the occupancy of CTCF and the cohesin subunit, SMC1, relative to transcriptionally engaged RNAPII and as a function of stimulus-dependent transcription in cultured mouse cortical neurons. We show that CTCF and cohesin are enriched at transcription start sites (TSS) and that their levels increase with the level of transcriptionally engaged RNAPII, suggesting that RNAPII facilitates the engagement of CTCF and cohesin. Unexpectedly, while neuronal stimulation causes widespread transcriptional activation, it resulted in the rapid genome-wide loss of SMC1 signals, including at the TSS of genes, loop anchors, and TAD boundaries. Activity-dependent reductions in cohesin were independent of CTCF but were mimicked by inhibiting topoisomerase IIb (TOP2B), which resolves torsional stress from DNA supercoiling. We show that neuronal stimulation elevates DNA supercoiling and that increasing torsional stress triggers the dissociation of SMC1 from chromatin. Overall, these results suggest that modulation of torsional stress could be a physiologically relevant mechanism of regulating cohesin engagement and chromatin architecture in neurons.

overall_design: RNA-seq in mouse cortical neurons

first: Morgan

last: Crewe

first: Ilse

last: Delint-Ramirez

first: Lance

last: Heady


title: RPA directly stimulates Mer3/HFM1 helicase processivity to ensure normal crossover formation in meiosis

status: Public on Nov 02 2025

city: PARIS

first: Valerie

last: Borde

address: 26 rue d'Ulm

country: France

institute: Institut Curie

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Meiotic crossover formation is critical for generating viable gametes and enhancing genetic diversity. The helicase Mer3 (HFM1 in humans) is a highly conserved factor essential for promoting crossovers and ensuring their proper distribution. Here, we identify replication protein A (RPA) as a direct interactor of budding yeast Mer3. We demonstrate that this interaction is conserved between human HFM1 and RPA. Cross-linking mass spectrometry and structural modelling with AlphaFold2 reveal a conserved and specific Mer3-RPA interface. Single-molecule magnetic tweezers assays demonstrate that direct RPA interaction is required for Mer3 helicase processivity under conditions of low DNA tension. Consistently, mer3 mutant deficient in RPA binding exhibit reduced crossover frequencies and accumulate unresolved recombination intermediates during budding yeast meiosis. Via genome-wide localisation experiments, we link this effect to a weakened recruitment to double-strand break sites of the mer3 mutant. Our findings provide mechanistic insights into coordination of meiotic recombination by the Mer3 helicase through interactions with the canonical DNA repair machinery, highlighting a conserved mechanism underlying crossover control during sexual reproduction.

sample_organism:
Saccharomyces cerevisiae
Saccharomyces mikatae

overall_design: 5 samples total: each comes from two independent replicates each of anti-FLAG ChIP in spo11∆-Mer3-His6FLAG3, Mer3-His6FLAG3 and Mer3-8A-His6FLAG3 S. cerevisiae cells at 3h (spo11∆-Mer3-His6FLAG3) and 3h and 4h (Mer3-His6FLAG3 and Mer3-8A--His6FLAG3) in meiosis combined with 10% of spike-in S. mikatae Zip4-His6FLAG3 cells at 4h in meiosis


title: Activated-ATF6α is an ER stress-inducing oncoprotein metabolically restricting immunosurveillance [bulk RNA-seq of Atf6 KO DEN/HFD]

status: Public on Nov 16 2025

city: La Jolla

first: Randal

middle: J.

last: Kaufman

state: CA

address: 10901 North Torrey Pines Road

department: Cancer Metabolism and Microenvironment Program, Center for Genetic Disorders and Aging Research NCI-Designated Cancer Center

country: USA

institute: Sanford Burnham Prebys Medical Discovery Institute

type: Expression profiling by high throughput sequencing

summary: Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related mortality with limited therapies. While endoplasmic reticulum (ER)-stress and the unfolded protein response (UPR) are implicated in HCC, the involvement of the UPR-transducer activating transcription factor 6 alpha (ATF6α) remains unclear. In contrast to the well-characterized role of ATF6α-activation as an adaptive response to ER-stress, we here demonstrate its hitherto unknown function as an ER stress-inducing oncoprotein and metabolic master-regulator restricting cancer-immunosurveillance. In human HCC, ATF6α-activation significantly correlated with reduced patient-survival, tumor-progression, local immunosuppression, and higher recurrence rates of liver-cancer upon hepatectomy. Hepatocyte-specific ATF6α-activation in mice induced progressive hepatitis with ER-stress, immunosuppression, and hepatocyte-proliferation. Concomitantly, activated-ATF6α increased glycolysis and repressed gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1). Restoring FBP1 expression prevented ATF6α-activation-related pathologies. Prolonged ATF6α-activation in hepatocytes triggered hepatocarcinogenesis, intratumoral T-cell infiltration, and nutrient-deprived immune-exhaustion. Immune-checkpoint blockade (ICB) efficiently restored immunosurveillance and dramatically reduced HCC. In line, HCC patients with a significantly higher ATF6α-activation signature presented complete response to ICB monotherapy. Targeting Atf6 via germline, hepatocyte-specific ablation, or therapeutic delivery of antisense-oligonucleotides dampened HCC in preclinical liver-cancer models. Thus, prolonged ATF6α-activation drives ER-stress, leading to aberrant glucose metabolism-dependent immunosuppression in liver cancer. Our findings propose persistently activated ATF6α as an oncoprotein, stratification-marker for liver-cancer ICB, and targetable therapeutic strategy against HCC.

overall_design: Gene expression analysis of Atf6 KO DEN/HFD mice using RNA-seq

first: Xin

last: Li

first: Cynthia

last: Lebeaupin

middle: J

first: Mathias

last: Heikenwälder


title: Improved spike-in normalization clarifies the relationship between active histone modifications and transcription

status: Public on Oct 29 2025

first: Alon

last: Goren

address: 9375 Gilman Dr

department: Department of Medicine

institute: University of California San Diego

summary: Spike-in normalization enables quantitative analysis of ChIP-sequencing (ChIP-seq) signal. Here we introduce a novel robust dual-spike-in normalization approach for ChIP-seq (ChIP-wrangler) and revisit recent claims that active histone marks are dependent on transcription. Concerned that previous studies improperly used spike-in normalization to arrive at their conclusions, we used ChIP-wrangler to show that acute depletion of RNA polymerase II has only a modest impact on the levels of H3K4me3 and H3K27ac. In line with other studies, our results provide proof that the maintenance of histone acetylation is not merely a consequence of ongoing transcription. Our innovative ChIP-seq normalization approach provides increased rigor and “guardrails” for successful spike-in normalization, and as applied here refines the understanding of the intricate crosstalk between RNA polymerase II activity and histone marks associated with transcription

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: HCT116-EF1a-OsTIR1-Rpb1 cells were treated with either 500nM Triptolide (Sigma-Aldrich T3652) or 500uM auxin (3-indoleacetic acid, Sigma-Aldrich #I3750) to degrade Rpb1 for 0, 1, and 4 hours. HeLa-S3 cells were treated with 500nM Triptolide (Sigma-Aldrich T3652) for 0, 1, or 4 hours. Sheared chromatin from D. melanogaster and S. cerevisiae were added as spike-in controls to all samples prior to immunoprecipitation. From every biological sample, a ChIP-input sample was prepared to assess the relative amounts of spike-in chromatin. ChIP-seq was perfomed using antibodies for H3K27ac, H3K4me3, H3K4me1, H3K36me3, and Rpb1 in HCT116-EF1a-OsTIR1-Rpb1 cells, and antibodies for H3K27ac, H3K4me3, H3K4me1, and Rpb1 in HeLa-S3 cells.

first: Lauren

last: Patel

first: Yuwei

last: Cao

first: Tianyao

last: Xu

first: Eduardo

last: Modolo

first: Tamar

last: Dishon

first: Lingzhi

last: Zhang

first: Eric

last: Mendenhall

first: Sven

last: Heinz

first: Itamar

last: Simon

first: Chris

last: Benner


title: PRC1 Mediates the Transcriptional Repressive Function of POGZ in Neurodevelopmental Gene Regulation

status: Public on Nov 03 2025

city: Harrisburg

first: Jessenia

last: Chavez

state: Pennsylvania

address: 4261 Williamsburg Dr, Apt. A

department: Biochemistry and Molecular Biology

institute: Pennsylvania State University

summary: Polycomb Repressive Complex 1 (PRC1) is a family of fundamental epigenetic regulators crucial for gene silencing and mammalian development. Elucidating the PRC1 composition and function in context- and stage-specific functions during differentiation and development is crucial in understanding the impact of PRC1-mediated transcriptional activity in these processes. This study focuses on the identification and characterization of POGZ, a high-risk Autism risk gene, as a novel component of the PRC1 complex in neural cells. Our biochemical analyses demonstrate that POGZ specifically interacts with the PRC1.6 complex to form the novel PRC1-POGZ complex. Functional assays indicate that POGZ elicits strong transcriptional repressor activity that is dependent on RING1B expression. ChIP-Seq studies determined that PRC1-POGZ localizes at neurodevelopmental genes in the embryonic mouse cortex. Although POGZ knockout (KO) does not compromise mESC pluripotency, POGZ ablation in neural precursor cells resulted in severe dysregulation of transcriptomic gene expression, marked by failed activation of key neural marker genes. Mechanistically, PRC1-POGZ target genes involved in multiple aspects of neuronal differentiation were differentially expressed in POGZ KO NPCs, which may explain the observed failed differentiation. The insights gained herein provide critical insights toward understanding how PRC1-POGZ function influences neural cell fate determination.

overall_design: To investigate the effects POGZ KO may have on the transcriptome of WT embryonic stem cells (ESCs) and differentiated neural precursor cells (NPCs). We generated a POGZ KO ESC line via CRISPR/Cas9 technology. POGZ WT and KO ESCs were differentiated in NPCs using a previously established protocol (Hanafiah, et al. 2020). We performed RNA-Seq on POGZ WT and KO ESCs (Day 0) and NPCs (Day 7). Duplicates of each genotype and time point were included in this experiment.

first: Zhonghua

last: Gao

first: James

last: Stafford


title: RNAPII and DNA supercoiling regulate cohesin engagement in neurons [ChIP-Seq]

first: Ram

last: Madabhushi

state: TX

overall_design: ChIP-seq in mouse primary cortical neurons

first: Morgan

last: Crewe

first: Ilse

last: Delint-Ramirez

first: Lance

last: Heady


title: Large scale cell-based transcriptome data treated with Jakyakgamcho-tang in PC12 cell

status: Public on Oct 24 2025

city: Daejeon

first: Su-Jin

last: Baek

address: 1672, Yuseong-daero

country: South Korea

institute: KOREA INSTITUTE of ORIENTAL MEDICINE

summary: Whole transcriptomic analysis in PC12 cells was conducted, comparing cells treated with a vehicle control to those treated with three different concentrations of JGT-E and JGT-W. All experiments were performed in triplicate.

overall_design: we constructed the pharmacological transcriptome data obtained through combinatorial conditions, such as extraction orders (individual herbs extracted or the herb-mixed JGT extracted), combination ratios (two herbs into 2:1, 1:1, and 1:2), two extracting methods (hot water or 70% ethanol).

first: Seongwon

last: Cha

first: Jin-Mu

last: Yi


title: Long-read single-cell RNA sequencing analysis of key genes and isoforms during corneal wound healing in Macaca fascicularis

city: guangzhou

first: ming

last: zhou

address: jinsui road 7

country: China

institute: Sun Yat-sen University,

summary: The repair of corneal damage is crucial for maintaining clear vision. When the corneal epithelium is damaged, epithelial cells at the corneal limbus quickly initiate a series of complex biological processes, including cell migration, extracellular matrix remodeling, and cell proliferation and differentiation, to promote repair and wound healing. However, comprehensive studies on the transcriptional heterogeneity of corneal limbal cell populations during migration, proliferation, and differentiation in the context of corneal epithelial injury repair are still lacking. In this study, we conducted a systematic analysis of five major cell types in the corneal limbus, including terminally differentiated cells of corneal epithelium (TDCE), basal cells (BC), transit-amplifying cells (TAC), limbal stem cells (LSC), and conjunctival cells (CC ), using high-throughput long-read single-cell RNA sequencing of corneal limbal tissues from Macaca fascicularis. The corneal epithelium was examined at three time points: before injury (0 days) and after injury (1 day and 3 days). The study focused on the migration, proliferation, and differentiation dynamics of these cells during different stages of corneal injury repair. Additionally, key regulatory genes and their RNA isoforms were investigated to uncover their roles in these processes. The results revealed that LSCs and BCs play pivotal roles in corneal epithelial healing, highlighting the regulatory functions of several key genes and their RNA isoforms in cell migration, proliferation, and differentiation. These include growth factors (e.g., IGF2), extracellular matrix components (e.g., FN1 and LAMC2), integrins (e.g., ITGB1 and ITGAV), and Keratin (e.g., KRT3, KRT12 and KRT6A). The study provides novel insights into the transcriptional landscape at the single-cell level during corneal epithelial damage repair, identifying important cell types and key regulatory genes with corresponding RNA isoforms.

overall_design: we extracted corneal epithelial cells from corneal tissues on days 0, 1, and 3 after corneal injury in cynomolgus monkeys (2 replicate samples were taken at each time point), and obtained single-cell full-length cDNAs using the 10× Genomics platform, and then used the HIT-scISOseq method for library construction and sequencing.

first: le-chun

last: ou

first: hu

last: chen

first: Zhuo-Xing

last: Shi


title: Testosterone exposure during fetal masculinization programming window determines the kidney size in adult mice

status: Public on Oct 23 2025

city: Turku

first: Petra

last: Sipilä

address: Kiinamyllynkatu 10

department: Institute of Biomedicine

country: Finland

institute: University of Turku

summary: To study the role of fetal testosterone exposure in the development of male mouse kidney, we compared fetal kidneys from WT and testosterone deficient Hsd17b3 KO mice at E16.5, after 2 day testosterone propionate or vehicle treatment.

overall_design: RNA-seq was performed from E16.5 kidneys from testosterone and vehicle treated WT and KO male mice.

first: Arttu

last: Junnila

first: Mats

last: Perk

first: Asta

last: Laiho


title: Systematic Pan-cancer Functional Inference and Validation of Hyper, Hypo and Neomorphic Mutations

status: Public on Oct 21 2025

city: New York

first: Somnath

last: Tagore

state: NY

address: William Black Building, 17th Floor, Lab 1708E

institute: Columbia University

summary: While the functional effects of many recurrent cancer mutations have been characterized, the TCGA repository comprises more than 10M non-recurrent events, whose function is unknown. We propose that the context specific activity of transcription factor (TF) proteins—as measured by expression of their transcriptional targets—provides a sensitive and accurate reporter assay to assess the functional role of oncoprotein mutations. Analysis of differentially active TFs in samples harboring mutations of unknown significance—compared to established gain (GOF/hypermorph) or loss (LOF/hypomorph) of function—helped functionally characterize 577,866 individual mutational events across TCGA cohorts, including identification of mutations that are either neomorphic (gain of novel function) or phenocopy other mutations (mutational mimicry). We performed RNA-seq profiles were generated by Pooled Library Amplification for Transcriptome Expression (PLATE-Seq), a highly controlled microfluidic assays for 37 breast cancer-specific PIK3CA mutations in MCF10A cell line. Validation using mutation knock-in assays confirmed 15 out of 15 predicted gain and loss of function mutations and 15 of 20 predicted neomorphic mutations.  This could help determine targeted therapy in patients with mutations of unknown significance in established oncoproteins.

overall_design:
To prospectively validate our functional inference for PIK3CA mutational status, we selected 37 breast cancer specificPIK3CAmutations, comprising 9 GOF, 5 LOF, and 20 NEO predicted events, whose functional relevance had not been previously assessed in the FASMIC repository. For this purpose, differential gene expression signatures were generated from MCF10 cell, following lentivirus-mediated knock-in of mutant PIK3CA cDNA vs. mock cDNA as negative control. RNA-seq profiles were generated by Pooled Library Amplification for Transcriptome Expression (PLATE-Seq), a highly controlled microfluidic assay described in Bush et al., 2017 (PMID: 28740083), for 37 breast cancer-specific PIK3CA mutations in MCF10A cell line.
*** Submitter declares that raw files will be deposited in dbGAP. ***

first: Samuel

last: Tsang

first: Gordon

last: B Mills

first: Andrea

last: Califano


title: Large scale cell-based transcriptome data treated with Jakyakgamcho-tang in HepG2 cell

summary: Jakyakgamcho-tang (JGT) is the simplest form of herbal medicine composed of Paeoniae Radix (PR) and Glycyrrhizae Radix at Rhizoma (GR), and has been used to treat muscle-related diseases and inflammation. However, the pharmacological effects of JGT may vary depending on the ratio of the constituent herbs and the main preparation conditions of the extraction method. Nevertheless, no gene expression dataset systematically reflecting these various variables has existed to date. In this study, a total of 498 transcriptome profiles were constructed with three concentrations and three replicates of RNA-seq data. It is structured to enable multidimensional analysis of the effects of various preparation conditions on gene expression by combining the ratio of PR:GR (2:1, 1:1, 1:2), solvent (water, 70% ethanol), and extraction method (combined decoction vs. separate decoction) of JGT, targeting three cell lines (HepG2, C2C12, and PC12). All raw and preprocessed data are deposited available through GEO, and standardized metadata and ingredient data are also provided. This dataset provides a foundation for exploring how traditional herbal medicine formulations affect cellular transcriptomic responses and can serve as a baseline for scientific optimization of herbal medicines.

overall_design:
Whole transcriptomic analysis in HepG2 cells was conducted, comparing cells treated with a vehicle control to those treated with three different concentrations of JGT-E and JGT-W. All experiments were performed in triplicate.
We constructed the pharmacological transcriptome data obtained through combinatorial conditions, such as extraction orders (individual herbs extracted or the herb-mixed JGT extracted), combination ratios (two herbs into 2:1, 1:1, and 1:2), two extracting methods (hot water or 70% ethanol).


title: Large scale cell-based transcriptome data treated with Jakyakgamcho-tang

summary: Whole transcriptomic analysis in C2C12 cells was conducted, comparing cells treated with a vehicle control to those treated with three different concentrations of JGT-E and JGT-W. All experiments were performed in triplicate.

overall_design: we constructed the pharmacological transcriptome data obtained through combinatorial conditions, such as extraction orders (individual herbs extracted or the herb-mixed JGT extracted), combination ratios (two herbs into 2:1, 1:1, and 1:2), two extracting methods (hot water or 70% ethanol), and three cell lines (muscle-related C2C12, neuropathic pain-related PC12, and drug metabolism-related HepG2).


title: Dedifferentiation-Driven Oncogenic Stemness Promotes Tumor-Sustaining Adaptability in the Intestinal Epithelium

status: Public on Oct 27 2025

city: Hoboken

first: ansu

last: perekatt

state: NJ

address: 507 River street

department: CCB

institute: Stevens Institute of Technology

summary: Intestinal tumors can arise either from mutations sustained in Lgr5⁺ stem cells (bottom-up) or through dedifferentiation of lineage-committed epithelial cells (top-down). Using a Smad4 loss-of-function and β-catenin gain-of-function mutant mouse model, we show that dedifferentiation-derived stem cells sustain tumorigenesis more effectively than mutant Lgr5⁺ cells in the endogenous crypts. Bulk and single-cell RNA sequencing revealed transcriptional reprogramming and the emergence of oncogenic villus-derived stem-like cells. Complementary in vivo and organoid studies suggest that dedifferentiation-derived oncogenic stem cells possess superior tumor-initiating and sustaining capacity.

overall_design: RNA was harvested from the intestinal villi epithelia of both wildtype (control) mice and Smad4 loss-of-function and β-catenin gain-of-function conditionally mutant mice. Samples were collected from three biological replicates for each treatment.

first: Kylee

last: Zgeib

first: Thompson

last: Hui

first: Simon

last: Garcia

first: Zahra

last: Hashemi

first: Shima

last: Nejati

first: Amartya

last: Singh

first: Crystal

last: Lim

first: Atharva

last: Inamdar

first: Binfeng

last: Lu

first: Ansu

last: Perekatt


title: RNAseq analysis of LU65 parental and cells that have acquired resistance to RMC-4998

status: Public on Oct 07 2025

city: Tampa

first: jiqiang

last: yao

address: 12902 USF Magnolia Drive

institute: moffitt cancer center

summary:
To investigate the transcriptinal alterations in RMC-4998 sensitive LU65 cells and cells that have acquired resistance to RMC-4998. The resistant cell lines of LU65 was generated following chronic treatment with RMC-4998.
We then performed gene expression profiling analysis using data obtained from RNA-seq of parental and resistant lines.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for  LU65 cells and their RMC-4998 resistant isogenic line. The experiment was perfomed in biological triplicates.

first: Eric

middle: B

last: Haura

first: Jiqiang

last: Yao

first: Paul

middle: A

last: Stewart

first: Hitendra

middle: S

last: Solanki


title: RNAseq analysis of Sotorasib sensitive and cells acquired resistance to Sotorasib

summary:
To investigate the transcriptinal alterations in Sotorasib sensitive and cells acquired resistance to Sotorasib. The Sotorasib resistant cell lines of H358 and LU65 were generated following chronic treatment with Sotorasib.
We then performed gene expression profiling analysis using data obtained from RNA-seq of parental and resistant lines.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for NSCLC cells (H358 and LU65) cells and their Sotorasib resistant isogenic lines (H358-AMGR and LU65-AMGR). The experiment was perfomed in biologicall triplicates.

last: stewart


title: dHyperCas12a enables multiplexed CRISPRi screens

status: Public on Oct 28 2025

city: Durham

first: Schuyler

last: Melore

state: North Carolina

address: 101 Science Dr

institute: Duke University

summary: Interactions between multiple genes or cis-regulatory elements (CREs) underlie a wide range of biological processes in both health and disease. Here, we combine a hyper-efficient version of Lachnospiraceae bacterium dCas12a (dHyperLbCas12a) with RNA Polymerase II expression of long CRISPR RNA (crRNA) arrays to enable efficient highly-multiplexed epigenome editing. We demonstrate that the dCas12a system is highly effective for high-throughput screens. We use four different dCas12a repressors and a ~900-member library of crRNA arrays containing four crRNAs each to target the promoters of essential genes or cell surface negative controls. This fitness screen allows us to compare the activity of different dCas12a repressors across many genomic loci.

overall_design:
To perform a combinatorial screen at the PER1 locus, we created two crRNA array plasmid libraries, with each construct containing six crRNAs and a unique barcode. The PER1-targeting library contains ~9,000 crRNA arrays and the Non-targteing library contains ~10,000 crRNA arrays. Each plasmid library was sequenced twice. These libraries were then transduced into cells at low MOI and selected with puromycin for ten days. On day ten they were rreated with different concentrations of dexamethasone, and sorted on PER1 expression. Top and bottom 12% PER1-expressing cells were sorted and sequenced, as well as bulk unsorted cells (Input).
To perform a fitness screen in A549 cells, we created two crRNA array plasmid libraries, containing the same spacers but either the As or Lb Cas12a direct repeat sequence, with each array construct containing four crRNAs. Each library contained ~900 crRNA arrays. These libraries were then transduced into A549 cells that stably express either dHyperLbCas12a-KRAB, dHyperLbCas12a-4xSID, dEnAsCas12a-KRAB, or dEnAsCas12a-4xSID repressors at low MOI (~0.2) and selected with puromycin. Three independent transductions were performed for each repressor cell line. Cells were passaged for three weeks post-transduction and cell pellets were collected at days 5, 7, 14, and 21 (post-transduction). crRNA array sequences were amplified from these cell pellets as well as the plasmid libraries and sequenced on the NextSeq2000.

first: Timothy

middle: E

last: Reddy

middle: M

first: Marisa

middle: C

last: Hamilton

first: Christian

middle: D

last: McRoberts Amador

first: Charles

last: Gersbach


title: Alternative splicing and differential gene expression during changes in endometrial receptivity in patients with recurrent implantation failure

status: Public on Oct 15 2025

city: Hangzhou

first: Jiucheng

last: Chen

state: Zhejiang

address: No.866 Yuhangtang Road

institute: Zhejiang University

summary:
Study question  : Are there changes in transcript levels as endometrial receptivity changes in patients with recurrent implantation failure (RIF), particularly in alternative splicing events (ASEs), differential expression genes (DEGs) and  immune cells   levels?
Summary answer: Changes in endometrial receptivity affect alternative splicing (AS), differential gene expression and immune cells, and the RNA-binding protein (RBP) KHDRBS3 likelymaybe？ Likely？ is involved in the dysregulation of alternative splicing.
What is known already: Endometrial receptivity is critical for RIF patients. Researchers have developed transcript level-based models to predict personalized endometrial assessment at WOI. Investigating alternative splicing dysregulation, immune cells and other transcriptional biomarkers in RIF patients may further help to predict endometrial receptivity and improve embryo implantation success.
Study design, size, duration: 90 endometrial samples were collected from fertile healthy controls (HC) during the menstrual cycle, including pre-receptive (PR) (luteinising hormone (LH)+3 days/LH+5 days), receptive (R) (LH+7 days) and post-receptive (PS) (LH+9 days) phases. 73 endometrial samples were taken from RIF patients on hormone replacement therapy (HRT) cycles, including PR (progesterone (P)+3 days), R (P+5 days) and PS (P+7 days) phases.
Participants/materials, setting, methods: Total RNA was extracted and sequenced for all 163 endometrial samples  . Bioinformatic analysis was used to comprehensively investigate the endometrial transcriptome at different stages of receptivity. We elucidated the biological significance of the universal alteration of alternative splicing in endometrial receptivity and further analyzed the role of immune cells and gene expression in this process. In addition, an ASEs-RBPs correlation network was constructed in the endometrial receptive period to evaluate the dysregulation of AS by RBPs.
Main results and the role of chance: Global splicing profiling of the four subgroups (HC: PR vs. R; HC: PS vs. R; RIF: PR vs. R; RIF: PS vs. R) consistently showed that skipped exons (SE) and mutually exclusive exons (MXE) were the most common changes in splicing events. These different ASEs occurred at high frequency and some of them could affect the coding potential of a transcript. A greater number of genes with different alternative splicing events (ASEGs) were identified between PR and R phases than between PS and R phases, and the same trend was observed for differentially expressed genes (DEGs). Both ASEGs and DEGs showed enrichment for pathways associated with cell function and adhesion, while DEGs were also enriched for cytokine and immune-related pathways. Immune cell prediction shows that changes in endometrial receptivity phases result in differences in the levels of CD8 T cells, resting NK cells and other immune cells. During the R phase, there was a significant decrease in CD8 T cells and resting NK cells, whereas monocytes and M0 macrophages were significantly increased compared to the endometrial PR phase in RIF patients. Similarly, analysis of immune cells showed a significant increase in CD8 T cells, M1 and M2 macrophages and a significant decrease in activated NK cells in the R phase compared to the PS phase of the endometrium in RIF patients. Some of these immune cells, such as NK cells and monocytes, are highly correlated with certain ASEs. Investigation of ASEs-RBPs networks suggested that KHDRBS3 may be a key regulator of splicing events.
Limitations, reasons for caution: The sample size needs to be increased and cover a variety of situations, such as different age, pathology, dietary habits, etc., and alsothe molecular experimental validation needs to be considered. The lack of direct comparisons between natural and HRT cycles in the same sample and molecular experimental validation need to be considered.
Wider implications of the findings: Comprehensive transcriptional analysis of the endometrium provide valuable insight into potential biomarkers related to endometrial receptivity and potential treatments for RIF patients.
Study funding/competing interest(s): This study was supported by Supported by the Program of National Natural Science of China (Grant No. 81701409). All authors declared that they have no conflicts of interest.

overall_design: Additionally, 73 samples were collected from RIF patients undergoing hormone replacement therapy (HRT) cycles, including PR (progesterone (P) +3 days), R (P +5 days), and PS (P +7 days).

first: Mao-li

last: Wang

first: Bing-jie

first: Han

last: Wu

first: Wen-bi

last: Zhang


title: BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells

status: Public on Oct 06 2025

first: Chen

state: Texas

address: 5901 FOREST PARK RD, NS6 218

summary: Self-renewing stem-like T cells promote the efficacy of cancer immunotherapy and are a heterogeneous population with sub-lineages demonstrating different degrees of stemness. At the apex of this hierarchy is long-term (LT) stem-like T cells with the highest capacity of persistence, repopulation and response to immune checkpoint inhibitors (ICI). However, the pathway that establishes the hierarchy of stemness in chimeric antigen receptor (CAR) T cells and its role in antitumor efficacy of CAR T cells are unclear. Here, we demonstrate that LT stem-like differentiation and antitumor immunity of CAR T cells are dose-dependently regulated by BACH2. Pre-infusion LT stem-like CAR T cells showed epigenetic activation of BACH2 and superior antitumor response in mice and humans. After clearing tumor in vivo, LT stem-like T cells emerged as a CAR subset that transcriptionally and epigenetically upregulated BACH2 and downregulated TOX. Loss-of-function experiments revealed an essential role of BACH2 in the antitumor response of CAR T cells and the transcriptional program of LT stem-like CAR T cells. In exhaustion-prone GD2 CAR T cells with high tonic signaling, we showed that quantitative control of BACH2 protein level by a small molecule drug fine-tuned the degree of stemness and exhaustion in CAR T cells. Chemically inducing temporal BACH2 activation during manufacture of GD2 CAR T cells imprinted greater antitumor immunity against solid tumor after infusion. Together, we show that BACH2 dosage establishes the hierarchy of stem-like CAR T cells and can be temporally and tunably controlled in CAR T cells to optimize differentiation and antitumor immunity.

overall_design: We performed single-cell ATAC+RNA sequencing on in vitro clutured CAR T cells and CAR T cells isolated from tumor bearing mice on day 20 after infusion. We performed scRNAseq on WT and BACH2 inducible knock out CAR T cells isolated from tumor bearing mice on day 7 after infusion. We performed ChIP-seq

first: Tuoqi

first: Ziang

last: Zhu

first: Taidou

last: Hu

first: Ying

last: Luo


title: Dabigatran protection against lipopolysaccharide induced endotoxemia is not mediated through its anticoagulant function

status: Public on Oct 03 2025

city: Ann Arbor

first: Vinitha

last: Jacob

state: MI

address: 8200 Medical Science Research Building III,  III, 1153 West Medical Center Drive

institute: University of Michigan

summary: Endotoxemia is a key feature of sepsis pathogenesis and has also been found to mediate the pathophysiology of multiple chronic inflammatory conditions.  In this work, we expand upon a model of endotoxemia due to lipopolysaccharide (LPS) using zebrafish and demonstrate that this model displays activation of inflammatory and pro-coagulant genes, impaired coagulation in response to endothelial injury, and signs of organ dysfunction.  An in silico analysis revealed that there were multiple associations between the RNA-seq signature of LPS treated embryos and the RNA-seq signature of genes and drugs involving diverse pathways.  An in vivo screen involving >1,500 FDA approved drugs identified multiple compounds spanning several drug categories that partially or completely prevented endotoxemic death.  Three small molecules including one anticoagulant dabigatran were identified through both the in vivo and in silico analyses.  Dabigatran, a direct thrombin inhibitor, significantly reduced the upregulation of inflammatory cytokines and pro-coagulant genes and completely protected zebrafish from endotoxemic death due to LPS.  However, other anticoagulants argatroban (direct thrombin inhibitor), and rivaroxaban and apixaban, (factor Xa inhibitors), conferred no such protection.  Lastly, prothrombin mutant fish displayed no increase in survival when treated with LPS.  These data together suggest that dabigatran protects zebrafish from endotoxemia through a mechanism independent of its anticoagulant effect.  In summary, our in silico and in vivo analyses reveals that dabigatran and several other novel small molecules prevent LPS induced endotoxemia and warrant further therapeutic exploration in inflammatory conditions, both acute and chronic.

overall_design: Zebrafish larvae that were 3 days post fertilization (dpf) were incubated with a lethal dose of LPS from Salmonella typhi and collected 3 hours post treatment.  Gene expression changes were compared to control untreated larvae.

first: Murat

last: Yaman

first: Jordan

last: Shavit


title: RNAseq data LUN 156 parental, adagrasib resistant and RMC-4998 resistant LUN156 tumors

first: jiqiang

last: yao

summary: LUN156 is a patient-derived xenograft (PDX) tumor model derived from 73-year-old male Chinese non-small cell lung cancer (NSCLC) patient with a tumor with a KRASG12C mutation.

overall_design:
PDX model development: To generate an animal tumor model, fresh tumor fragments were obtained from hospitals with informed consents from the patients in accordance with protocols approved by the Hospital Institutional Ethical Committee (IEC). The tumors were cut into 30 to 60 mm3 fragments after arrival at CRO animal facility and serially passaged after implanting subcutaneously into BALB/c nude mice.
Briefly, five to six-weeks-old female Balb/c nude mice were purchased from Vital River Lab Animal Technology Co. Ltd., Beijing, China. Animals were held for a minimum of 7 days for acclimation prior to the beginning of study. Animals were housed in individually ventilated cages (IVC) under specific pathogen free (SPF) conditions with access to standard diet and water ad libitum. During the study period, the animals were monitored daily for any effects of tumor growth and treatments on normal behavior, such as mobility, food, and water consumption. Study-related parameters like body weight and tumor volume (tumor volume = ((width)2 × length)/2, where width and length are measured in mm) were measured twice weekly.
Recovered tumor fragments of about 15-30 mm3 in volume were implanted subcutaneously into right flanks of Balb/c female nude mice and mice were randomized by blocks when average tumor sizes reached ~200 mm3 in volume into three treatment groups with three mice in each group. The animals were administered vehicle for RMC-4998 formulation as a control, RMC-4998 100 mg/kg, and adagrasib 100 mg/kg as a daily treatment through oral gavage for 28 days, and end of study tumor samples were collected. In an independent study, to derive a stable adagrasib or RMC-4998 resistant (adagrasib-R or RMC-4998-R) LUN156 PDX tumor model, animals were treated with 100 mg/kg of each inhibitor for 90 days to determine on-treatment tumor relapse. After treatment period, the mouse showing on-treatment tumor relapse was collected (Passage 0 (P0)). The 30-50 mm3 volume tumor fragments from P0 were further subcutaneously implanted into the right flanks of female Balb/c nude mice and allowed to grow. Once the tumor became palpable (70-100 mm3), respective KRASG12C inhibitor treatments were provided daily and observed for tumor growth until the tumor reached an average of 1,000 mm3 in volume (P1). The animal from each inhibitor resistant cohort showing the least doubling time for a tumor to grow was selected and passaged further to generate P2. The in vivo serial passage procedure with respective KRASG12C inhibitor was repeated until P5 to ensure resistant phenotype in LUN156 tumor model, and samples were frozen for efficacy and single dose pharmacodynamic use. During these passages, snap frozen tumor fragments were collected for resistance mechanism analyses

first: Ida

last: Aronchik

first: Eric

last: Haura

first: Ethan

last: Ahler

first: Jiqiang

last: Yao

first: Hitendra

last: Solanki


title: RNA-seq analysis of NK-92 cells expressing Vaccinia virus (VACV) poxin (encoded by the B2R gene)

status: Public on Oct 31 2025

first: In-Hwan

last: Jang

address: 125, Gwahak-ro, Yuseong-gu, Daejeon, Republic of Korea

department: Immunotherapy Research Center

institute: Korea Research Institute of Bioscience and Biotechnology

summary: Transcriptional profiling of Poxin-NK-92 cells compared to control cells.

overall_design: Bulk RNA-seq of experiment: ctrl-NK-92, Poxin-NK-92 (A stable cell line was established by lentiviral infection, and positive cells were selected using fluorescence-activated cell sorting (FACS)). Samples were derived from total RNA extracted from 24 hours cultured NK-92 cells.

first: Ling-Zu

last: Kong

first: Tae-Don

last: Kim


title: Structural and functional changes in the gastrointestinal tract of the ACTA2 R179H mouse model of multisystemic smooth muscle dysfunction syndrome

city: Boston

first: Rhian

last: Stavely

state: MA

address: 185 Cambridge Street, CPZN, 6100

department: Pediatric Surgery

institute: Massachusetts General Hospital

summary: Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS) is a rare disorder caused by ACTA2 mutations, including the R179H variant, which disrupts actin polymerization and smooth muscle contractility. While cardiovascular complications dominate its clinical presentation, gastrointestinal (GI) dysfunction significantly impacts quality of life. To investigate the structural, functional, and cellular basis of gut dysmotility in MSMDS, we studied the ACTA2 R179H mouse model and reviewed clinical data from 24 MSMDS patients. Patients exhibited severe gut dysmotility, with 75% requiring medication for chronic constipation. ACTA2 mutant mice displayed cecal and colonic dilatation, reduced intestinal length, and disrupted colonic migrating motor complexes (CMMCs). Delayed whole-gut transit and impaired contractile responses to electrical and pharmacological stimulation were observed. Transcriptomic analysis revealed significant actin cytoskeleton-related gene changes in smooth muscle cells, and immune profiling identified increased lymphocytic infiltration. Despite functional abnormalities, enteric neuronal populations remained unchanged. These findings establish ACTA2 mice as a robust model for studying GI pathology in MSMDS, elucidating the role of smooth muscle dysfunction in gut dysmotility. This model provides a foundation for developing targeted therapies aimed at restoring intestinal motility by directly addressing actin cytoskeletal disruptions in smooth muscle cells.

overall_design: Use of 10X Genomics technology to analyze single-nuclei transcriptomics in single nuclei suspensions of muscularis propria from the colon of Myh11-Cre:Acta2R179Hfl/+ mouse model of Multisystemic Smooth Muscle Dysfunction Syndrome (MSMDS)

first: Ahmed

last: Rahman

first: Leah

last: Ott

first: Christopher

middle: Y

last: Han

first: Kensuke

last: Ohishi

first: Ryo

last: Hotta

first: Alan

last: Burns

first: Sabyasachi

last: Das

first: Emily

last: Da Cruz

first: Diana

last: Tambala

first: Mark

last: Lindsay

first: Patricia

middle: L

last: Musolino

first: Allan

last: Goldstein


title: Anti-Glycan Reactivity in Humans is Driven by the Selection of B cells Utilizing Private Antibody Gene Rearrangements that are Affinity Maturated in Germinal Centers

status: Public on Oct 01 2025

city: Birmingham

first: Rodney

middle: Glenn

last: King

state: AL

address: 411 Shelby Interdisciplinary Biomedical Research Building 1825 University Boulevard

department: Microbiology

institute: University of Alabama at Birmingham

summary: The human antibody repertoire is broadly reactive with carbohydrate antigens represented in the universe of all living things, including both the host/self- as well as the commensal microflora-derived glycomes. Here we have used BCR receptor cloning and expression together with single-cell transcriptomics to analyze the B cell repertoire to the ubiquitous N-acetyl-D-glucosamine (GlcNAc) epitope in human cohorts and dissect the evolutionary history of this predominant class of antibodies. We find that circulating anti-GlcNAc B cells exhibiting canonical BMem phenotypes emerge rapidly after birth and couple this observation with evidence for germinal center-dependent affinity maturation of carbohydrate-specific B cell receptors in situ during early childhood. Direct analysis of individual B cell clonotypes reveals they exhibit strikingly distinct fine-specificity profiles for palettes of GlcNAc containing moieties. These results suggest that a generalized, exposure to complex environmental glycans drives the steady state anti-glycan repertoire.

overall_design: CD19 expressing B cells and Group A Carbohydrate binding B cells were facs sorted and subjected to scRNAseq and BCR seq

first: James

last: New

middle: F

last: Fucile

first: Amanda

middle: R

last: Callahan

first: Julia

middle: N

last: Burke

first: Wayne

last: Duck

first: Alexander

last: Rosenberg

first: John

last: Kearney

middle: G


title: IFNg shapes macrophage inflammatory responses by STAT1 isoform-specific epigenetic and transcriptional mechanisms [RNA-Seq]

status: Public on Sep 30 2025

city: Wien

first: Birgit

last: Strobl

address: Veterinarplatz 1

department: TZG

country: Austria

institute: VetMedUni

summary: Interferon gamma (IFNg) is a pivotal cytokine that activates macrophages and shapes their response to subsequent inflammatory stimuli. Here, we investigated the distinct roles of STAT1 isoforms, STAT1alpha and STAT1beta, in IFNg-induced epigenetic remodelling and subsequent responses to lipopolysaccharide (LPS) in primary macrophages. We show that the STAT1 C-terminal TAD, which is missing in the STAT1beta isoform, is required for both H3K27 acetylation and deacetylation in response to IFNg. Notably, H3K27 deacetylation was associated with AP-1 motifs rather than STAT1 binding, suggesting indirect regulatory mechanisms. Functionally, IFNg pretreatment suppressed the induction of anti-inflammatory and virus response genes, including a subset of IFN-stimulated genes (ISGs), in response to LPS, while enhancing the expression of a distinct set of ISGs. Mechanistically, the STAT1 C-terminal TAD was critical for IFNg-mediated inhibition of LPS-induced enhancer activation at key regulatory genes, such as Il10 and Irak3, which are involved in negative feedback of toll-like receptor (TLR) signalling. Conversely, cooperative gene activation by IFNg and LPS was largely independent of the STAT1 C-terminal TAD, with notable exceptions, such as Ido1 and Tgtp1. Genome-wide analysis indicated that IRF1 and IRF8, rather than STAT1 homodimers, predominantly mediate in IFNg-induced H3K27 acetylation and transcription factor network analysis identified additional regulators integrating IFNg and LPS responses. Together, these findings reveal gene- and isoform-specific roles of STAT1 in coordinating IFNg-dependent chromatin remodelling and transcriptional cross-regulation, providing new insights into the control of inflammation and innate immunity.

overall_design: RNA-seq profiling of murine bone marrow-derived macrophages at several time points and treatments

first: Mojoyinola Joanna

last: Akagha

first: Grigorios

last: Georgolopoulos

first: David

last: Martin

first: Katrin

last: Meissl

first: Lena

last: Amenitsch

first: Claus

last: Vogl

first: Matthias

last: Farlik

first: Nikolaus

last: Fortelny

first: Florian

last: Halbritter

first: Thomas

last: Decker

first: Mathias

last: Müller


title: L-Chiral Hydrogel Accelerates Wound Healing via Lactate-Mediated RNF123 K57 Lactylation

status: Public on Oct 17 2025

city: Shanghai

first: Ruizhe

last: He

address: No. 639, Zhizaoju Road

institute: Shanghai Jiao Tong University

summary: Chronic wounds, characterized by delayed healing and persistent inflammation, represent a major clinical burden with limited effective therapies. Inspired by the stereoselective interactions in biological systems, we developed an L-chiral hydrogel composed of self-assembled helical nanofibers from L-histidine derivatives, which preferentially enriches lactate to promote wound repair. Compared to D-chiral and racemic hydrogels, the L-chiral hydrogel significantly accelerated wound closure in rat models, achieving nearly 90% healing by day 14 and reducing healing time to 16-17 days. Transcriptomic and metabolomic analyses revealed enhanced wound response pathways and elevated lactate levels in the L-chiral group. Mechanistically, enriched lactate induced K57 lactylation of RNF123, mediated by AARS1, altering RNF123 conformation and weakening its binding to UBAC1. This modification enhanced ubiquitination and processing of NF-κB p105 into p50, inhibiting the NF-κB pathway and promoting angiogenesis via enhanced endothelial cell migration, tube formation, and sprouting. Rescue experiments with lactate inhibitor Oxamate and exogenous lactate confirmed the lactate-dependent mechanism. This study not only demonstrates a drug-free chiral biomaterial for efficient wound healing but also unveils the molecular role of lactate-mediated lactylation in mechanoregulating inflammation and vascularization, offering new insights for regenerative medicine.

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: This dataset contains two parts: the first part is RNA-seq from animal experiments, collecting wound margin tissues from rats treated with L-chirality hydrogel and negative control group on day 14 for RNA-seq analysis; the second part is RNA-seq of Human Umbilical Vein Endothelial Cells (HUVEC), constructing stable transfected cell lines of RNF123 wild-type and K57R HUVEC for RNA-seq analysis.


title: Transcriptomic analysis of flies at different days of starvation

status: Public on Oct 14 2025

first: Yanhui

last: Hu

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary:
Purpose: Adaptation to changing environmental conditions is essential for survival. When animals adapt to nutrient shortage, intra-organ responses as well as inter-tissue crosstalk mechanisms need to be mounted to coordinate whole-body energy homeostasis. To address this we collected flies at different day of starvtion for transcriptomic analysis
Methods: snRNA-seq analysis of whole-body flies (without heads) at fed, day2 and day5 of starvation
Results: The data provides information of transcriptome alternations related to adaptation of staravtion, including expression of metabolic genes and organ communications.
Conclusions: Expression of many metabolic genes were changed during staravtion and oenocytes play a role in this adaptation

overall_design: The following genotypes were used: PromE-gal4, Tub-gal80ts

first: Huang

last: Kerui

first: Dibra

last: Indira

first: Chen

last: Weihang

first: Hu

last: Yanhui

first: Perrimon

last: Norbert


title: IFNg shapes macrophage inflammatory responses by STAT1 isoform-specific epigenetic and transcriptional mechanisms

first: Birgit

last: Strobl

overall_design: ChIP-Seq for histone marks (H3K27ac and H3K4me1) in murine bone marrow-derived macrophages at several time points and treatments

first: Mojoyinola Joanna

last: Akagha

first: Grigorios

last: Georgolopoulos


title: Human kinome CRISPR knockout screen in H358 parental and sotorasib resistant H358 cells

first: jiqiang

last: yao

summary: A human kinome CRISPR knockout screen in H358 parental and sotorasib-R H358 cells using Addgene pooled libraries (#75314).

overall_design: Parental cells were cultured with DMSO, while resistant cells were cultured with sotorasib for 2 weeks. Integrated sgRNAs were amplified from genomic DNA and sequenced. We analyzed depleted sgRNAs in sotorasib-R H358 cells compared to reference or parental cells.

first: Eric

last: Haura

first: Aobuli

last: Xieraili

first: Hitendra

last: Solanki


title: Flt3L -expanded conventional type I dendritic cells formed in the tumor prime “stem-like” T cells in the draining lymph nodes to evoke enhanced responses to immunotherapy [2]

status: Public on Oct 02 2025

city: Perth

first: Jesse

middle: David

last: Armitage

state: WA

address: 35 Stirling Hwy, Crawley

department: School of Biomedical Sciences

country: Australia

institute: University of Western Australia

summary: Immune checkpoint blockade (ICB) evokes anti-tumor immunity through the reinvigoration of tumor-specific T cell responses but it is only effective in a subset of patients. T cell differentiation status is a critical determinant of response, with less differentiated cells demonstrating an enhanced capacity to proliferate following ICB. Given recent data indicating that conventional type 1 dendritic cells (cDC1) maintain precursor exhausted (TPEX) cells, we hypothesized that expansion of cDC1s could enhance responses to ICB. Treatment of mice with Flt3L simultaneously expanded cDC1s and CD62L+SLAMF6+CD8+ T cells in both tumors and draining lymph nodes. The formation of these CD62L+SLAMF6+ CD8+ T cells is dependent on the transcription factor Myb, CCR7+ XCR1+DCs and lymph node egress. Hence, we demonstrate that the lymph node is a critical site for the effect of Flt3L on T cell differentiation state. We hypothesized that the promotion of this phenotype would enable more effective responses to ICB. Indeed, the combination of Flt3L and anti-CTLA4 led to significantly enhanced therapeutic responses and was associated with the emergence of a unique CD8+ T cell subset characterized by the expression of IL-21R.

overall_design: Single cell RNA-TCR profiling of whole AT-3 or AT-3-FLT3L tumors, +/- aCTLA4 treatment. Matched draining lymph nodes (dLNs) were also harvested from a proportion of these mice. tumor (n=6 per group) and dLN samples (n=3 per group) were labelled lipid-modified oligonucleotides (LMOs) for cell hashing and pooled into 4 samples for sequencing.


title: Epigenomic and transcriptomic profiling of cnidocyte subtypes in the sea anemone Nematostella vectensis [RNA-Seq]

status: Public on Oct 05 2025

city: Jerusalem

first: Itamar

last: Kozlovski

address: Alexander Silberman Institute of Life Sciences

department: Ecology, Evolution and Behavior

country: Israel

institute: The Hebrew University of Jerusalem

summary: Cnidarians, including corals, sea anemones, and jellyfish, possess specialized stinging cells called cnidocytes that function in prey capture and defense. These cells represent a striking evolutionary innovation and include distinct types such as venom injecting nematocytes and mechanically acting spirocytes. While their biomechanics and transcriptional regulation have been studied extensively, little is known about their epigenetic regulation. Here, we combined epigenetic profiling with RNA sequencing in the sea anemone Nematostella vectensis to explore regulatory programs underlying cnidocyte diversity. We identified cell type specific regulatory elements in promoter and enhancer regions and linked them to distinct gene expression programs. This analysis revealed fundamental differences between nematocytes and spirocytes and uncovered a previously unrecognized nematocyte population that expresses the nep3 toxin but lacks most other toxins. These findings highlight the complexity of cnidocyte regulation and suggest greater cellular diversity within this defining cnidarian cell type than previously appreciated.

overall_design: This study investigates the chromatin and transcriptional programs underlying cnidocyte specialization in the sea anemone Nematostella vectensis. Cnidocyte types (Ncol3⁺ and Nep3⁺) and their negative counterparts were isolated from adult polyps by fluorescence activated cell sorting (FACS). CUT&Tag (H3K27ac) and RNA-seq were performed in four biological replicates per condition to identify cell type-specific regulatory regions and gene expression programs. The design allows direct comparisons between positive and negative populations for each reporter line.

first: Adrian

last: Jaimes-Becerra

first: Daria

last: Aleshkina

first: Matan

last: Levy

first: Yehu

last: Moran


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis - bulk RNA-Seq

city: Oxford

first: Alison

last: Simmons

address: John Radcliffe Hospital/Headley Way

department: The MRC Weatherall Institute of Molecular Medicine

country: United Kingdom

institute: University of Oxford

summary: The aim of this study was to investigate how over expression of  transcription factors alters the gene expression program of primary human colonic fibroblasts. Fibroblasts isolated from healthy donor biopsies were transduced with lentiviral vectors to over-express TWIST1 or OSR2, or with empty vector as a control, followed by bulk RNA sequencing. The goal was to identify transcriptional pathways and effector genes regulated by these factors, with a focus on extracellular matrix organization, morphogen signaling, and fibroblast functional states.

overall_design: Primary human colonic fibroblasts were isolated from endoscopic biopsies of healthy donors and expanded in vitro. Cells were transduced with lentiviral vectors to over-express TWIST1 or OSR2, or with empty vector as a control, followed by puromycin selection. Total RNA was extracted from each condition using the RNeasy Plus Micro kit (Qiagen). Bulk RNA sequencing libraries were prepared by Novogene and sequenced on an Illumina platform to a depth of approximately 50 million paired-end reads per sample.

first: Colleen

last: McGregor

first: Xiao

last: Qin

first: Marta

last: Jagielowicz

first: Tarun

last: Gupta

first: Zinan

last: Yin

first: Verena

last: Lentsch

first: David

last: Fawkner-Corbett

first: Vy

last: Lai

first: Paula

last: Gomez Castro

first: Esther

last: Bridges

first: Chloe

last: Hyun-Jung Lee

first: Huei-Wen

last: Chuang

first: Lei

last: Deng

first: Anna

last: Aulicino

first: Renuka

last: Teague

first: Sorayya

last: Moradi

first: Jun

last: Park

first: Jeongmin

last: Woo

first: Kexin

last: Xu

first: Ruchi

last: Tandon

first: Nicole

last: Cianci

first: Jan

last: Bornschein

first: Ling-Pei

last: Ho

first: Paulina

last: Siejka-Zielinska

first: Zoe

last: Christoforidou

first: Sarah

last: Hill

first: Johannes

last: Lehmann

first: Rhea

last: Kujawa

first: Paola

last: Vargas Gutierrez

first: Carol

last: Cheng

first: Maria

last: Greco

first: Katherine

last: Baker

first: Mark

last: Bignell

first: Bruce

last: George

first: Eve

last: Fryer

first: Michael

last: Vieth

first: Agne

last: Antanaviciute


title: Flt3L -expanded conventional type I dendritic cells formed in the tumor prime “stem-like” T cells in the draining lymph nodes to evoke enhanced responses to immunotherapy [1]

first: Jesse

last: Armitage

overall_design: Single cell RNA profiling of whole 24JK or 24JK-FLT3L tumors. Harvested day 16, n=5 per group


title: Single cell gene expression profile from mouse lung tissue

first: Jae-Won

last: Shin

address: 1011 N University Ave Room K1030, Ann Arbor, MI 48109

summary: The majority of the cells consist of immune cells. From lung tissue after repetitive bleomycin-induced fibrotic injury, followed by treatment with immune cloaking gel-coated mesenchymal stromal cells

overall_design: The cells were isolated by lung tissue digestion with enzyme mix from Tumor Dissociation Kit (#1119; Miltenyi), followed by filtration through 40-micron strainer and confirmation of cell viability above 90%. n = 2-3 mice were pulled for each group.

first: Ik-Sung

last: Cho

first: Amal

last: Yaghmour

last: Sanborn

first: Maria Paula

last: Zappia

first: Maxim V

last: Frolov

first: Jalees

last: Rehman


title: Identification of major transcription factor regulating gene signautures associated with jakyakgamcho-tang in PC12 cells

status: Public on Oct 13 2025

first: Su-Jin

last: Baek

address: 1672, Yuseong-daero

institute: KOREA INSTITUTE of ORIENTAL MEDICINE

summary: Neuropathic pain (NP) is a chronic condition caused by complex molecular mechanisms. Due to the challenges in NP treatment, it is crucial to develop novel targeting strategies that can help elucidate its molecular mechanisms. Jakyakgamcho-tang (JGT) has significant therapeutic potential; however, its precise mechanism of action remains unclear. In this study, we systematically investigated the key transcription factors and mechanisms of action of water/ethanol extract of JGT (WJGT/EJGT) and their compounds using transcriptome analysis. We identified key transcription factor involved in NP pathogenesis by profiling transcriptome and histone ChIP-seq from NP model. We analyzed gene expression changes in PC12 cells treated with JGT extract to determine its key mechanisms and transcriptional regulators. To further validation the novel mechanisms and targets of JGT and its key compounds, we conducted in vitro experiments. The PDGFRB pathway was significantly downregulated by JGT extracts, with Fos identified as a key transcription factor regulating JGT-induced target gene expression. Furthermore, we identified key compounds among seven compounds that were regulated by the PDGFRB pathway and Fos expression. Notably, the targets modulated by JGT extracts and its key compounds were associated with inflammation. Our findings suggest that targeting the PDGFRB pathway and its key transcription factor, Fos, is a potential therapeutic strategy for NP. This study provides novel insights into the mechanism and transcriptional regulator underlying JGT and its key compounds in NP treatment.

overall_design: Total whole transcritome profiles treated with water extract of Jakyakgamcho-tang (JGT) and  ethanol extract of JGT in PC12 cell.


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis

first: Alison

last: Simmons

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

overall_design: Refer to individual Series


title: LBR and LAP2 mediate heterochromatin tethering to the nuclear periphery to preserve genome homeostasis

city: Zürich

first: Puneet

last: Sharma

state: Zürich

address: Otto-Stern-Weg 3

department: Institute of Biochemistry

country: Switzerland

institute: ETH

summary: In most eukaryotic cells, euchromatin is localized in the nuclear interior, whereas heterochromatin is enriched at the nuclear envelope (NE). This conventional chromatin organization is established by heterochromatin tethering to the NE, however its importance for cellular homeostasis is largely unexplored. Peripheral heterochromatin localization relies on redundant NE-tethering systems. One tether is constituted by the lamin B receptor (LBR) in mammals, but the enigmatic nature of the other tethers has hampered functional analyses. Here we demonstrate that the downregulation of abundant, ubiquitous NE proteins can induce the global detachment of heterochromatin from the NE. Among these factors, we identify LBR and LAP2 as major players in bulk heterochromatin attachment to the NE in pluripotent and differentiated mammalian cells. Their loss leads to repositioning of heterochromatin to the nuclear interior, changes in chromatin accessibility, deregulation of gene expression including activation of antiviral innate immunity, and defects in cell fate determination.

overall_design: HCT116 and mESCs cells depleted of specific nuclear envelop proteins were subjected to RNA-, ATAC-, ChIP- and HiC-sequencing to decipher transcriptional and accessibility changes in these cells.

first: Renard

last: Lewis

first: Virginia

last: Sinigiani

first: Noura

last: Maziak

first: Krisztian

last: Koos

first: Cristiana

last: Bersaglieri

first: Ivo

last: Zemp

first: Caroline

last: Ashiono

first: Constance

last: Ciaudo

first: Peter

last: Horvath

first: Juanma

last: Vaquerizas

first: Raffaella

last: Santoro

first: Ulrike

last: Kutay


title: RB modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions [RNA-Seq]

first: Hanjun

last: Lee

state: Massachusetts

address: 77, Avenue Louis Pasteur

department: Department of Genetics

summary: The retinoblastoma protein (RB) is a well-characterized repressor of E2F transcriptional activity that controls genes involved in cell proliferation during the G1-phase. Here, we examine the effect of RB on chromatin organization and uncover a non-canonical role for RB in which it promotes the removal of cohesin from insulators and thereby induces the expression of adjacent genes. We identify that RB colocalizes with cohesin across the human genome. During mitosis, RB facilitates the removal of cohesin from CTCF sites, with this effect persisting into early G1, impacting loop formation and extrusion at topologically associating domain (TAD) boundaries. Chromosome conformation capture assays revealed that RB reduces insulation at TAD boundaries and promotes enhancer-promoter interactions marked by histone 3 lysine 27 acetylation. In this way, RB enhances the transcription of hundreds of genes beyond the E2F transcriptional program, expanding our understanding of this key tumor suppressor and cell cycle regulator.

overall_design: RNA-seq for RB WT or RB KO hTERT1-RPE1 cells synchronized in G1 or S phase

first: Ioanna-Maria

last: Gkotinakou

first: Michael

last: Lawrence

first: Ioannis

last: Sanidas


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis - Visium Spatial Transcriptomics

first: Alison

last: Simmons

summary: Crohn's disease often presents with fistulae, abnormal tunnels connecting the intestine to the skin or other organs. Despite the profoundly adverse impact of fistulae on patient morbidity, the molecular basis of their formation remains unclear, largely due to the challenge of capturing intact fistula tracts and their inherent heterogeneity. Here, we construct an unbiased, subcellular-resolution spatial expression atlas of 62 intestinal fistulae spanning diverse anatomical locations. We describe fistula-associated epithelial, immune and stromal cell states, revealing abnormal zonation of growth factors and morphogens linked to establishment of tunnelling anatomy. We identified fistula-associated stromal (FAS) fibroblasts assembled in concentric layers, forming a proliferative, lumen-adjacent zone (LAZ) underlying surface neutrophil and macrophage-rich granulation tissue, followed by active lesion core FAS cells all encircled by quiescent, pro-fibrotic outer zone (FOZ) fibroblasts. We mapped fistula tract ECM architecture and demonstrated FAS populations locate to different collagen structures, exhibiting functional properties spanning proliferation, migration and active ECM remodelling, to dense collagen deposition and fibrosis. We define niches supporting epithelialization of fistula tunnels and a putative precursor FAS population detected at the base of ulcers in non-penetrating Crohn’s. This precursor population co-localises with inflammatory as opposed to pro-fibrotic SPP1+ macrophages and fails to induce developmental transcription factors, observed in FAS populations located in fistula tracts.  Our study demonstrates that common molecular pathways and cellular niches underpin fistulae arising at different intestinal locations and reveal the cellular protagonists of fistula establishment and persistence. Our resource will inform development of model systems and interventions that mitigate aberrant fibroblast activity while preserving their regenerative properties in Crohn’s.

overall_design: This study employed Visium FFPE spatial transcriptomics to investigate the molecular landscape of Crohn's disease across different phenotypic manifestations, including fistulizing, stricturing, and inflammatory subtypes, in comparison to healthy controls. A total of 36 slides were analyzed, comprising tissue sections from patients diagnosed with Crohn's disease and non-diseased controls. The spatially resolved transcriptomic profiling was performed on formalin-fixed, paraffin-embedded (FFPE) tissue samples, enabling high-resolution analysis of gene expression within the spatial context of the tissue architecture. Some slides contain more than one tissue section (see meta data).

first: Colleen

last: McGregor

first: Tarun

last: Gupta

first: Zinan

last: Yin

first: Esther

last: Bridges

first: Verena

last: Lentsch

first: David

last: Fawkner-Corbett

first: Chloe

middle: H

first: Ruchi

last: Tandon

first: Katherine

last: Baker

first: Anna

last: Aulicino

first: Jan

last: Bornschein

first: Paulina

last: Siejka-Zielinska

first: Zoe

last: Christoforidou

first: Marta

last: Jagielowicz

first: Kexin

last: Xu

first: Sorayya

last: Moradi

first: Maria

last: Greco

first: Cyril

last: Lai

first: Jana

last: Koth

first: Mark

last: Bignell

first: Bruce

last: George

first: Eve

last: Fryer

last: Vieth

first: Agne

last: Antanaviciute


title: RB modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions [ChIP-Seq]

first: Hanjun

last: Lee

overall_design: ChIP-seq (SMC3, acSMC3, H3K27ac, H3K27me3) for RB WT or RB KO hTERT1-RPE1 cells that are asynchronous or synchronized in G1 or S phase or for hTERT1-RPE1 cells that expressed constitutively active RB

first: Ioanna-Maria

last: Gkotinakou

first: Michael

last: Lawrence

first: Ioannis

last: Sanidas


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

status: Public on Sep 26 2025

city: Institute

first: Gerardo

last: Flores-Iga

state: West Virginia

address: Integrated Research and Extension Building

department: Biology

institute: West Virginia State University

summary: The ability to sense capsaicin has been predominantly characterized in mammals through activation of the transient receptor potential vanilloid subtype 1 (TRPV1) in nociceptive neurons, yet how this compound is sensed in organisms lacking TRPV1 remains poorly understood, often leading to an overreliance on TRP-based mechanistic explanations that are contradictory and inconclusive. Here, we show that capsaicin modulates feeding behavior and activity in Drosophila melanogaster, which lacks a TRPV1 ortholog, through a mechanism involving the chemosensory system that is independent of metabolic state and the gut. Integration of single-nuclei brain transcriptomics (snRNA-seq) with bulk RNA sequencing revealed sex-specific transcriptomic reprogramming, engaging a common desensitization axis through Drosulfakinin (Dsk) in peptidergic neurons and Clk regulon-associated signatures in glial cells. Using functional genetics, we identified the gustatory system as the primary mediator of this response, involving Gr64f+ neurons and Gr64e. Together, our study defines a noncanonical, TRP-independent mechanism of capsaicin detection, revealing an alternative chemosensory framework and gives a glimpse of sex-dependent transcriptional adaptations that may shape behavioral responses.

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 ZT6â??12.
RNA-seq profiling of wildtype Berlin-K and humanized md>TRPV1 flies at Day5 of dietary intervention.

first: Umesh

middle: K

last: Reddy


title: RB modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions


title: Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming [CUT&Tag]

city: Chongqing

first: Zhe

last: Chen

address: 1 Yixueyuan Road, Yuzhong District

institute: Chongqing Medical University

summary: Leukemia stem cells (LSCs) drive acute myeloid leukemia (AML) initiation, relapse, and chemoresistance, yet the core post-translational events governing LSC formation and maintenance remain elusive. Here, through phosphoproteomic profiling of normal hematopoietic stem and progenitor cells (HSPCs) versus LSC-enriched population, we identify DEK phosphorylation as a critical modification during leukemogenesis. Functional studies in MLL-AF9- and HOXA9/MEIS1-driven AML mouse models, as well as patient-derived xenografts (PDXs), demonstrate that DEK deficiency impairs LSC maintenance and AML development. Moreover, DEK deletion enhances LSC chemosensitivity to the standard-of-care combination of azacitidine and venetoclax (Aza/Ven), whereas DEK overexpression confers robust chemoresistance. Mechanistically, DEK recruits the transcription factor GABPA to drive overexpression of transcriptional cofactor PBX3, a key oncogenic driver in AML, thereby sustaining a leukemogenic transcriptional program. This DEK-GABPA interaction strictly depends on DEK phosphorylation at Ser301/303/306/307 (the 4S site), which stabilizes the conformation of the DEK-GABPA complex. We demonstrate CK2 as the upstream kinase that directly phosphorylates DEK-4S site. Importantly, inhibition of DEK phosphorylation through 4S site mutations or treatment with a clinical-stage CK2 inhibitor CX-4945 selectively depletes LSCs while sparing normal HSPCs. Furthermore, combining CX-4945 with venetoclax promotes LSC apoptosis and suppresses the PBX3-mediated leukemogenic transcriptional program, exhibiting synergistic anti-AML effects both in vitro and in vivo. Collectively, our findings uncover a previously unrecognized phosphorylation event (DEK-4S phosphorylation) that sustains LSCs and establish the CK2-DEK axis as a promising LSC-specific therapeutic strategy in AML.

overall_design: Dekfl/fl;Tie2-Cre (Dek-cKO) and Dek-Ser306A/Ser308A/Ser311A/Ser312A(4S-A) AML mice were sorted, followed by DEK- and GABPA-CUT-Tag-seq. L-GMPs from MLL-AF9-driven Dekfl/fl and Dek-cKO AML mice were sorted, followed by PBX3-CUT-Tag-seq.


title: Resilience to Endoplasmic Reticulum Stress Mitigates Calcium-Dependent Membrane Hyperexcitability Underlying Late Disease Onset in Spinocerebellar Ataxia Type 6

status: Public on Sep 24 2025

city: Los Angeles

first: Genevieve

last: Konopka

address: 650 Charles Young Drive South, 73-214 CHS

department: Neurobiology

institute: UCLA David Geffen School of Medicine

summary: An enduring puzzle in many inherited neurological disorders is the late onset of symptoms despite expression of function-impairing mutant protein early in life. We examined the basis for onset of impairment in Spinocerebellar ataxia type 6 (SCA6), a polyglutamine ataxia with late-onset cerebellar neurodegeneration. In a mouse model of SCA6, we identified a homeostatic response that engages the unfolded protein response early in disease. This protective response provided insight into endoplasmic reticulum (ER) stress-mediated cerebellar Purkinje neuron membrane hyperexcitability as a driver of disease. Age-dependent impairment of chaperone-mediated compensation for ER stress increased calcium-dependent Purkinje neuron membrane excitability. Redundant pathways of the unfolded protein response mediate this resilience to ER stress. ER stress-related decompensation applies also to other late-onset human cerebellar ataxia. These studies elucidate a mechanism of resilience connecting aberrant proteostasis and calcium-dependent intrinsic membrane hyperexcitability to explain delayed disease onset more widely in age-dependent neurodegenerative disease.

overall_design: mRNA sequencing was performed on a NovaSeq instrument (Illumina, Inc.) with ~155 million reads and 150 bp paired-end reads. 5 cerebellum samples from each genotype from each age were used. Samples were prepared individually and pooled together to reduce batch effects. The samples were then demultiplexed into fastq files and statistics were collected using FastQC (Babraham Bioinformatics). The fastq files were trimmed using Trimmomatic (Bolger et al., 2014). 150 bp reads were aligned using STAR (Dobin et al., 2013), and the percent of unique reads were calculated. Raw read counts per gene per sample were calculated using HTSeq (Anders et al., 2015). Outliers were removed based on principal component analysis and hierarchical clustering. Differential gene expression analysis was performed using DESeq2 (Love et al., 2014).

first: Vikram

last: Shakkottai


title: RB modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions [Mnase-Seq]

overall_design: MNase-seq for RB WT or RB KO hTERT1-RPE1 cells


title: CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation


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

status: Public on Sep 28 2025

city: Xi’an

first: Jiaxi

last: Xu

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: OTUD4 regulates pancreatic cancer progression via Hippo/YAP axis

status: Public on Sep 21 2025

city: Shenyang

first: Shuaike

last: Qu

address: Liaoning Province,Shenyang city,Shenbei New District,79 Puhe Road

institute: China Medical University

summary: The over-activation of Hippo/YAP axis was often observed in pancreatic adenocarcinoma (PAAD), while the detailed mechanism is not totally understood. Recent studies demonstrated that the ubiquitin modification, which controlled the protein stability of YAP, played important roles in Hippo signaling and PAAD progression. In order to understand the underlying link between YAP protein stability and Hippo activity in PAAD progression, we carried out GSEA bioinformatic analysis coupled with siRNA screening and identified OTUD4 as an important effector for Hippo signaling in PAAD. OTUD4, which was highly expressed in PAAD tissue, correlated with Hippo target gene expression in PAAD tissues. Depletion of OTUD4 significantly reduced the activity of Hippo/YAP axis and hampered PAAD progression. Mechanism studies revealed that OTUD4 could interact with YAP and promote YAP K48-linked poly-ubiquitination and degradation in PAAD. In conclusion, our study identified an interesting regulation mechanism between OTUD4 and Hippo signaling in PAAD, while targeting OTUD4 could be a plausible strategy for PAAD therapy.

overall_design: RNA-seq profiling of AsPC-1 cells transfected with siControl or siOTUD4 for 48h


title: Phosphorylated DEK sustains leukemia stem cells by enabling PBX3-driven transcriptional reprogramming [ATAC-seq]

overall_design: L-GMPs(Lin-Sca-1-c-Kit+CD16/32+CD34+) from MLL-AF9-driven Dek+/+, Dekfl/fl;Tie2-Cre (Dek-cKO) and Dek-Ser306A/Ser308A/Ser311A/Ser312A(4S-A) AML mice were sorted, followed by ATAC-seq.


title: Identification of a shared drug-tolerant persister program in triple-negative breast cancer across treatments and patients [CITE-seq]

status: Public on Sep 22 2025

city: Paris

first: Céline

last: Vallot

address: 26 Rue D'Ulm

institute: Institut Curie

summary: Acquisition of resistance to anti-cancer therapies is a multistep process, which initiates with the survival of drug tolerant persister cells. Understanding the mechanisms driving the emergence of drug tolerant persister cells remains challenging, primarily because of their limited accessibility in patients. Here, using multiple patient-derived models to isolate persister cells, we show these cells are transcriptionally plastic in vivo and return to a common treatment-naïve like state upon relapse, regardless of the treatment they have been exposed to. We reveal hallmarks of the persister state in TNBC across treatment modalities: high expression of basal keratins together with activation of a stress response and inflammation pathways. HER2+ breast and lunger cancer cells also activate these hallmarks of drug tolerance in response to targeted therapies. Leveraging gene regulatory networks, we identify AP-1, NFKB and IRF/STAT as the key drivers of this hallmark persister state. As a proof of concept, we show that FOSL1 - an AP-1 member - is sufficient to drive cells to the persister state by binding enhancers and reprogramming the transcriptome of cancer cells. On the contrary, cancer cells without FOSL1 have a decreased ability to reach the persister state. By defining hallmarks of drug persistence to multiple therapies of the standard of care in TNBC, our study provides a resource to design novel combination therapeutic strategies to limit resistance.

overall_design: CITE-seq was performed on a pool of 5 samples MDA-MB-468 (GOF VPR control, VPR FOSL1 gRNA2, VPR FOSL1 gRNA3, HA control and HA FOSL1)

first: Léa

last: Baudre

first: Grégoire

last: Jouault

first: Justine

last: Marsolier


title: Retinal polyunsaturated fatty acid supplementation reverses aging-related vision loss in mice

city: Irvine

first: Dorota

last: Skowronska-Krawczyk

address: Gavin Herbert Eye Institute

institute: University of California, Irvine

summary: The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD). ELOVL2 (Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level  of its promoter is currently one of the best predictors of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Short-term and long-term intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals improved visual function and reduced accumulation of ApoE and C3d in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature similar to younger retinas. Finally, we present  human genetic data showing significan t association of two variants in the ELOVL2 locus with the onset of intermediate AMD, underlining the translational importance of our findings. In sum, our study identifies potential therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.

overall_design: snRNA-seq profiling of retinas from 3-month-old and 18-month-old wildtype C57BL6/J mice

first: Fangyuan

last: Gao

first: Emily

last: Tom

first: Qing

last: Nie

first: Yutong

last: Sha


title: RB modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions [ChIP-seq]

first: Hanjun

last: Lee

overall_design: SMC3 ChIP-seq for RB WT or RB KO hTERT1-RPE1 cells that are synchronized in G1 or mitotic phase

first: Ioanna-Maria

last: Gkotinakou

first: Michael

last: Lawrence

first: Ioannis

last: Sanidas


title: RB modulates chromatin organization by regulating cohesin-dependent loops and enhancer-promoter interactions [HiChIP]

overall_design: H3K27ac HiChIP for RB WT or RB KO hTERT1-RPE1 cells that are synchronized in G1 via contact inhibition


title: A novel oncolytic neutrophil phenotype is induced by IL-10R inhibition [CITE-seq]

status: Public on Sep 17 2025

city: New York

first: Yacine

last: Marouf

address: 413 E 69th St

department: MCC

institute: Weill Cornell Medecine

summary: While the impact of neutrophils on antitumor T cells has been an active area of study, fewer studies have focused on the potential of neutrophils to directly impact tumor cells. Here we asked whether neutrophils have the capacity to directly kill tumor cells independently of T cells. We find that anti-CD40-based therapy, when combined with interleukin 10 (IL-10) receptor blockade, initiates a Batf3-dependent pathway in which IL-12 and interferon gamma (IFNγ) secretion results in oncolytic neutrophil activity. Using a combination of microscopy, single-cell, and functional assays, we observe that killing of tumor cells by neutrophils is dependent on physical contact and degranulation. This degranulation-mediated killing is associated with an atypical dynamic invasive neutrophil phenotype. In line with our preclinical findings, our phase 1 trial of anti-CD40 shows that circulating IL-12, IFNγ, and IL-10 increase in response to anti-CD40, while our phase 1b/2 PRINCE study shows that lower circulating IL-10 is associated with favorable overall survival specifically among anti-CD40-treated patients. Finally, we find that neutrophil expansion with granulocyte colony stimulating factor (G-CSF) is associated with improved overall survival specifically in patients treated with anti-CD40, suggesting that this pathway may be amenable to therapeutic intervention in patients with advanced cancer.

overall_design: C57BL/6 wild type and Batf3 knockout mice were intradermally inoculated with B16F10 murine melanoma cells on their flanks, and eight days later, they received Isotype control, or a combination of anti-CD40/MPL/anti-IL-10R (CMI). Twelve hours post-treatment, the B16F10 tumors were harvested and processed into single-cell suspensions. Single-cell RNA sequencing (scRNA-Seq) was subsequently performed on these FACS-sorted cell suspensions.

first: Danny Nejad

last: Khalil

first: Ricardo

last: Gomez

first: Amit

last: Regev

first: Fadi

last: Samaan

first: Sadna

last: Budhu

first: Daniel

last: Hirschhorn

first: Isabell

last: Schulze

first: Jessica A.

last: Lavery

first: Nicholas

last: Ceglia

first: Samuel

last: Freeman

first: Vivien I.

last: Maltez

first: Jaynia

last: Garcia

first: Nathan

last: Suek

first: Chien-Huan (Gil)

last: Weng

first: Christopher R.

last: Cabanski

first: Sébastien

last: Monette

first: Yevgeniy

last: Romin

first: Yanyun

last: Li

first: Ronan

last: Chaligne

last: Yellin

first: Tibor

last: Keler

first: Deena M.

last: Maurer

first: Anne-Laure

last: Flamar

first: Lucia

last: Morgado-Palacin

first: Levi

last: Mangarin

first: James

last: Harding

first: Wungki

last: Park

first: Jaclyn P.

last: Lyman

first: Stephen

last: Maddock

first: Mark H.

last: O’Hara

first: Ghassan K.

last: Abou-Alfa

first: Robert H.

last: Vonderheide

first: Eileen M.

last: O’Reilly

first: Ronald N.

last: Germain

first: Jedd D.

last: Wolchok

first: Taha

last: Merghoub


first: Hanjun

last: Lee

overall_design: ATAC-seq for RB WT or RB KO hTERT1-RPE1 cells that are asynchronous or synchronized in G1 or S phase or for hTERT1-RPE1 cells that expressed constitutively active RB for 0 h, 24 h, or 72 h

first: Ioanna-Maria

last: Gkotinakou

first: Michael

last: Lawrence

first: Ioannis

last: Sanidas


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis - scRNA-Seq

first: Alison

last: Simmons

overall_design: Cells from small intestinal tissue samples in patients with Crohn's disease and healthy controls were profiled using single cell RNA-Seq. Cell pools were either enriched for epithelium (EPCAM+), immune (CD45+) or stromal cells (CD45- EPCAM-). Samples were subjected to 5' scRNA sequencing with feature barcoding, yielding Gene expression, CITE-seq and TCR information.

first: Colleen

last: McGregor

first: Tarun

last: Gupta

first: Zinan

last: Yin

first: Esther

last: Bridges

first: Verena

last: Lentsch

first: David

last: Fawkner-Corbett

first: Chloe

first: Ruchi

last: Tandon

first: Katherine

last: Baker

first: Anna

last: Aulicino

first: Jan

last: Bornschein

first: Paulina

last: Siejka-Zielinska

first: Zoe

last: Christoforidou

first: Marta

last: Jagielowicz

first: Kexin

last: Xu

first: Sorayya

last: Moradi

first: Maria

last: Greco

first: Cyril

last: Lai

first: Jana

last: Koth

first: Mark

last: Bignell

first: Bruce

last: George

first: Eve

last: Fryer

last: Vieth

first: Agne

last: Antanaviciute


title: ChIP-seq in parental and resistant non-small cell lung cancer (NSCLC) cells

status: Public on Sep 16 2025

first: sihong

last: chen

address: Wenhua Road

institute: Shenyang Pharmaceutical University

summary: Crotonylation is a crotonyl-coenzyme A (CoA)-mediated post-translational modification best known for its roles in epigenetic regulation. Histone lysine crotonylation (Kcr) has been reported to be involved in tumor-related biological functions such as DNA damage repair and immune infiltration. Here we find that abnormal reduction of histone Kcr significantly correlates with a poor response to epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in resistant models of lung cancer cell lines, and in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. The crotonyl-CoA-producing enzyme ACSS2 is the key regulator of the resistance-related change of crotonylation. Quantitative crotonylomic, transcriptomic and epigenomic analyses reveal that EGFR-TKI resistance is accompanied by reduced levels of histone 3 lysine 56 crotonylation (H3K56cr) on chromatin, which inhibits transcription of HNF1A and activates the PI3K/AKT signaling pathway.

overall_design: To uncover how histone Kcr regulates target genes and downstream signaling pathways to mediate EGFR-TKI resistance, ChIP-sequence was performed in HCC827 cells and HCC827_Er cells.

first: Sihong

last: Chen

first: Xiaoyuan

last: Wang

first: Youwei

last: Su


title: Transcriptional Response to Non-Steroidal Anti-Inflammatory Drugs and Tryptophan Supplementation

city: Philadelphia

first: Nicholas

last: Lahens

state: PA

address: Smilow Center for Translational Research 10-110 3400 Civic Center Blvd, Bldg 421

department: ITMAT

institute: University of Pennsylvania

summary: Non-steroidal anti-inflammatory drugs (NSAIDs) are popular choices for the mitigation of pain and inflammation; however, they are accompanied by adverse effects in the gastrointestinal and cardiovascular systems. We compared the effects of placebo, naproxen, a traditional NSAID, and celecoxib, a cyclooxygenase (COX)-2 inhibitor, in the plasma of healthy volunteers. We found a decrease in tryptophan and kynurenine levels in the plasma of those volunteers treated with naproxen. Based on these findings we treated mice with control, celecoxib, or naproxen diets, and examined their effects on the heart and jejunum transcriptomes. Additionally, we tested if tryptophan treatment rescued the transcriptional effects of naproxen treatment.

overall_design: RNA-Seq profiling of heart or jejunum tissue from female C57BL/6 mice following three weeks of treatment with celecoxib, naproxen, tryptophan, naproxen + tryptophan, or control. Celecoxib and naproxen treatments were provided through diet, while tryptophan treatment was administered through intraperitoneal injection. Tissue samples were collected and sequenced in four different experimental batches with 5-8 mice per combination of treatment and experiment. The first experimental batch collected from heart tissue of mice treated with control or naproxen diets also included 5 male mice per treatment.

first: Soumita

last: Ghosh

first: Kayla

last: Barekat

first: Soon-Yew

last: Tang

first: Katherine

last: Theken

first: Emanuela

last: Ricciotti

first: Arjun

last: Sengupta

first: Robin

last: Joshi

first: Weiming

last: Hu

first: Frederic

last: Bushman

first: Aalim

last: Weljie

first: Tilo

last: Grosser

first: Garret

last: FitzGerald


title: An epigenetic repressor TRIM66 dictates monogenic olfactory receptor expression, neural activity, and olfactory behavior

first: Yalei

last: Kong

address: No. 280, Chongqing South Road

institute: Shanghai Jiao Tong University

summary: Olfactory receptor gene choice is an intricate example of monogenic and monoallelic expression, where one out of over 1000 receptor genes is tran- scribed in each olfactory sensory neuron. This process involves expression of multiple olfactory receptor genes in immature neurons, followed by silencing of all but one receptor genes during maturation. However, the molecular identity of the repressors remains mysterious. Here, we discover TRIM66 as a key repressor. Multiple receptor genes are retained at low levels in most single mature OSNs after deletion of Trim66, leading to decreased expression of the vast majority of olfactory receptor genes. Mechanistically, TRIM66 can bind to, assembly, and repress olfactory receptor enhancers, thereby silencing extra olfactory receptor genes. Functionally, deletion of Trim66 leads to severe defects in the olfactory information processing and innate olfactory behaviors. Our study provides the missing link in understanding the transition from polygenic to monogenic olfactory receptor expression.

overall_design:
To examine the potential role of Trim66 in olfactory receptor (OR) expression, we generated KO and cKO mouse lines and assessed changes in receptor expression following Trim66 deletion (For bulk RNA-seq and scRNA-seq data).
To investigate the mechanisms of OR gene regulation by Trim66, we performed ChIP-seq in the MOE of WT mice using antibodies against TRIM66, ATF5, EZH2, and YY1 (For ChIP-seq data).
To evaluate changes in chromatin accessibility, We further performed ATAC-seq in the MOE of Trim66 knockout mice (For ATAC-seq data).
We further performed Hi-C in Trim66 knockout mice to investigate 3D genome organization (For Hi-C data).
Additionally, we carried out CUT&Tag experiments in Olfr1507-expressing OSNs isolated from Olfr1507-ires-tdTomato; Trim66 knockout mice using antibodies against H3K27ac and H3K27me3 to profile histone modifications (For H3K27ac, H3K4me1, H3K9me3, and H3K27me3 data).
To explore the mechanisms of olfactory receptor gene regulation by Trim66, We performed ATAC-seq for the Olfr1507 OSNs in the MOE of Olfr1507-ires-tdTomato; Trim66 knockout mouse (For Olfr1507 OSNs ATAC-seq data ).

first: Hongqiang

last: Bao

first: Qian

last: Li


title: Raw transcriptomic data of JQX3 after inoculation with Plasmodiophora brassicae

status: Public on Sep 14 2025

city: Beijing

first: xinyue

last: wang

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

institute: China Agricultural University

summary: JQX3 plants were cultivated in soil until the two-leaf-one-core stage. The roots were then dipped and inoculated with a Plasmodiophora brassicae suspension at a concentration of 1 × 10⁸ spores/mL. Root samples were collected at 0, 3, and 10 days after inoculation. Total RNA was extracted using the RNAprep Pure Polysaccharide Polyphenol Plant Total RNA Extraction Kit and subsequently used for transcriptomic analysis. Three biological replicates were included for each time point.

overall_design: RNA-seq profiling of JQX samples at 0 DAI (CK), 3 DAI and 10 DAI.

first: Xinyue

last: Wang

first: Zengxi

last: Wu

first: Jinqi

last: Zhang

first: Shaoqi

last: Yang

first: Zixian

last: Jia

first: Yu

first: Yuhang

last: Zheng

first: Ping


title: JAX Study 9- RNA-seq of male KOLF2.2J hiPSC-derived cortical brain organoids homozygous null for eight different transcription factors.

status: Public on Sep 08 2025

city: Hinxton

first: MorPhiC

last: Consortium

address: Wellcome Genome Campus

institute: EMBL-EBI

summary: This study aims to phenotype iPSC-derived cortical brain organoids that contain homozygous null alleles for transcription factors expressed in the early neuroectoderm. Null alleles were generated using insertion of a premature termination codon with frameshift (PTC+1). RNA-seq data was generated at the indicated day post initiation of differentiation from hiPSCs. The study included the homozygous null alleles for the following transcription factors: EMX2, FOXG1, POU3F2, SOX1, HES5, SOX21, POU3F1 and SP8. This analysis provided insight into the impact of loss of function for these transcription factors in cortical brain organoid differentiation.

overall_design: The study involved the generation of RNA-seq on 39 samples. Different time points of differentiation to cortical brain organoids were chosen according to the initiation of the transcription factor in wildtype cells within this differentiation scheme. Three biological replicates were run for gene. Additionally, three biological replicates were run of wildtype KOLF2.2J cells (the parental male cell line in which the KOs were generated) under the same differentiation conditions in the different time points. This comprehensive design allowed for a robust analysis of the effects of transcription factor manipulation on brain organoid formation.

first: Juliana

last: Diniz

first: Bill

last: Skarnes

first: Paul

last: Robson