title: Trp53 Mutation-Mediated mTORC1 Inhibition and Inflammation Suppression Confer Resistance to Checkpoint Immunotherapy

city: Pittsburgh

first: David

middle: Shihong

state: PA

address: 5051 Centre Avenue

department: Immunology

institute: University of Pittsburgh

summary: p53 is a critical tumor suppressor gene that inhibits cancer development by regulating cell cycle arrest, apoptosis, DNA repair, and metabolism. However, recent studies examining TP53 mutations in cancer immunotherapy have yielded inconsistent results, likely due to differences in tumor mutational burden (TMB) and the context-dependent roles of specific p53 mutants. In this study, we assessed the function of G242V and S258I Trp53 mutations in MC38 cells in the context of immunotherapy by generating Trp53 deletion and observed significantly enhanced responses to anti-PD-1 therapy. We next characterized how the Trp53 deletion in MC38  tumor cells alters the immune response. To this end, we performed single-cell RNA and paired single-cell TCR sequencing (scRNAseq and scTCRseq) of anti-PD-1 treated Trp53CON and Trp53KO MC38 tumors on day 11 after tumor cells inoculation.

overall_design: CRISPR-Cas9 was used to knockout p53 in the MC38 tumor cell line. WT and KO MC38 cells were inoculated into C57BL/6J mice and treated with anti-PD-1 immune checkpoint blockade therapy.

first: Binfeng

last: Lu


title: Tracking tau and cellular responses in human iPSC-microglia from uptake to seedable secretion in extracellular vesicles

status: Public on Aug 31 2025

city: Oxford

first: Sam

last: Washer

state: Oxfordshire

address: NDMRB, Roosevelt Drive

department: Centre for Medicines Discovery

country: United Kingdom

institute: University of Oxford

type: Expression profiling by high throughput sequencing

summary: The templated spread of tau aggregates in tauopathies has been attributed to neuron-to-neuron spread, but microglia have also been implicated, in mouse studies. Here we examine in detail the uptake, processing, release and seeding of tau using human iPS-derived microglia (iMGL). We show that tau is taken up by iMGL via LRP1 and heparan sulfate proteoglycans, with a role for LRRK2 in LRP1 trafficking, and that phagocytosed fibrils can escape into the cytoplasm. Tau monomer has minimal effect on iMGL, but recombinant or brain-derived tau fibrils induce a shift towards chemokine and interferon response subtypes, alongside downregulation of homeostatic and MHC genes. Endogenous tau protein is undetectable in iMGL, and monomeric tau is digested to completion, but fibrillar tau is degraded inefficiently and becomes phosphorylated on two specific residues. Finally, undegraded tau is released, including secretion as fibrils visualised by cryo-EM within extracellular vesicles, and can seed downstream neurons

overall_design: iPSC-microglia (iMGL) derived from SCF_856-03-06 were treated to either vehicle control, labelled recombinant monomeric tau (1ug/mL), labelled recombinant fibrilar tau (1ug/mL), Tau PHF extracted from AD patient brain (Eli Lily, pooled from 5 patients, 0.25ug/mL), HT7 Tau Ab immunodepleted brain sample (Eli Lily, pooled from 5 patients, matched to samples 4,5,6,22), Tau PHF extracted from AD patient brain (Oxford Brain Bank, patient 1, 2 or 3), Tau PHF extracted from healthy patient brain (Oxford Brain Bank, patient 1,2,3), for 24 hours. Cells were then harvested, snap frozen, and sent to Azenta for RNA extraction, QC, library prep, and bulk RNAseq

first: Maria

middle: K

last: Karabova

first: Anna

last: del Ser-Badia

first: Anne

last: Hedegaard

middle: J

first: Zeynep

last: Baykam

first: Iolanda

last: Vendrell

first: Darragh

middle: P

last: O'Brien

first: Errin

last: Johnson

first: Charlotte

middle: E

last: Melia

first: Teige

last: Matthews-Palmer

first: Rishi

last: Matadeen

first: Alessia

last: Santambrogio

first: Michael

middle: A

last: Metrick II

first: Michele

last: Vendruscolo

first: Kenneth

middle: S

last: Kosik

first: Theresa

last: Day

first: William

last: James

first: Sally

last: Cowley


title: Transferrin Receptor contributes to PANoptosis in thyroid cancer

city: Dali

first: Zhiqiang

last: Ma

state: Yunnan

address: No.35 Renmin South Road

country: China

institute: Dali Bai Autonomous Prefecture People's Hospital

summary: PANoptosis is a novel type of cell death triggered by the cross-talk of three types of cell death (necrosis, apoptosis, and pyroptosis). Nevertheless, the molecular mechanisms associated with PANoptosis in thyroid cancer (TC) remain uncharted. Therefore, this study explored the effect of TFRC on PANoptosis in TC cells in vitro.

overall_design: This study performed an mRNA-seq for K1 cells from the KD-NC (K1 cells transfected with negative vector) and KD-TFRC (K1 cells transfected with TFRC shRNA) groups

first: Shungao

first: Jingwei

last: Shen

first: Hong

last: Liu

first: Hua

last: Yang

first: Yuqin

last: Hu

first: Simeng

last: Ying


title: Anti-Müllerian Hormone Ameliorates Uterine DNA Damage Response and Prevents Pregnancy Complications in Doxorubicin-Treated Mice

city: Boston

first: Ngoc Minh Phuong

last: Nguyen

state: MA

address: 55 Fruit st

department: Pediatric Surgical Research Laboratory

country: USA

institute: Massachusetts General Hospital andHarvard Medical School

summary: Anti-Müllerian hormone (AMH) has emerged as a potential fertoprotective agent, demonstrating its strongest protective effects against Doxorubicin (DOX)-induced ovarian toxicity. While chemotherapy’s gonadotoxic impact on ovaries has been extensively studied, its effects on the uterus remain poorly understood. In this study, we investigated DOX-induced uterine damage and assessed the protective role of AMH co-treatment. DOX triggered DNA double-strand breaks in the uterine myometrium, activating Cdkn1a and other Tp53 pathway genes, and was linked to increased dystocia in pregnant mice. AMH co-treatment counteracted these effects by reducing γ-H2AX-positive DNA damage foci, suppressing Tp53 pathway activation, and improving pregnancy outcomes. These findings establish AMH as a promising therapeutic agent for preserving uterine integrity during chemotherapy, opening new avenues for fertility preservation and improved reproductive health in cancer patients.

overall_design: To elucidate the impact of DOX and AMH on prepubertal uterine function, we administered two weekly doses of DOX (3mg/kg) to prepubertal mice (postnatal day 25). A comparative group received concurrent administration of AMH. Uteri were harvested at 4 and 24 hours post-treatment for bulk RNA sequencing analysis.

first: David

last: Pepin


title: Transcriptomic of ileocecal junction of DBA/1 mice with spontaneous arthritis (SpAD)

city: Chihuahua

first: Susana

middle: Aideé

last: González-Chávez

state: Chihuahua

address: Circuito Universitario Campus II

department: Facultad de Medicina

country: Mexico

institute: Universidad Autónoma de Chihuahua

summary:
The spontaneous arthritis (SpAD) model in the DBA/1 mouse strain resembles the Spondyloarthritis human disease, including the intestinal inflammation characterized by loss of the integrity of the epithelial barrier and increased permeability. The transcriptome characteristics in this mouse model's gut are very scarce.
Transcriptome analysis was performed using DNA microarrays of ileocolic junction of DBA/1 strain mice with spontaneous arthritis (SpAD).

overall_design: The spontaneous arthritis (SpAD) model was generated in the DBA/1 mouse strain as described for the model. After sacrifice, the ileocolic junction was dissected, and total RNA was extracted and hybridized on Affymetrix microarrays.

first: Susana Aideé

first: César Francisco

last: Pacheco-Tena


title: Differential gene expression in the knee of DBA/1 mice with spontaneous arthritis (SpAD) compared to healthy BALB/c mice

summary:
The DBA/1 mouse strain produces spontaneous arthritis (SpAD) characterized by an inflammatory process and changes in the joint structures that resemble human spondyloarthritis. Normally, it is the hind paws that are analyzed in this model and information on the alterations in the knee is very scarce.
Transcriptome analysis was performed using DNA microarrays of knees of DBA/1 strain mice with spontaneous arthritis (SpAD) and BALB/c strain mice as a control.

overall_design: The spontaneous arthritis (SpAD) model was generated in DBA/1 mouse strain as described for the model. After sacrifice, the knees of diseased mice and healthy BALB/c mice were dissected. Total RNA was extracted from the knees and hybridized on Affymetrix microarrays.

first: César

middle: F


title: Optogenetic-Programmable Human Embryo Models Elucidate the Interplay Between Tissue Architecture and BMP4 Signaling at the Onset of Gastrulation

city: New York

first: Riccardo

last: De Santis

address: 1230 York Ave

institute: The Rockefeller univeristy

summary: The spatiotemporal regulation of morphogenetic signals, along with their interaction with local tissue mechanics, guides morphogenesis and determines the shape and form of the embryo (Valet et al., 2022 PMID: 34754086; Pfeifer et al., 2024 PMID: 38181658). However, how these signals precisely integrate into developmental circuits remains poorly understood. Here, we took advantage of a light-inducible strategy (De Santis et al., 2021 PMID: 34799555) to induce BMP4 signaling with precise spatial coordinates to study epiblast symmetry breaking and its interplay with tissue mechanics at the onset of gastrulation. Light-controlled BMP4 induced SMAD1-5 phosphorylation, resulting in the differentiation of extra-embryonic amnion cells and relied on a tension-dependent induction of the WNT (Muncie et al., 2020 PMID: 33207224) and NODAL pathways for mesoderm and endoderm differentiation. In micropattern gastruloids (Warmflash et al., 2014), tissue tension signals through YAP1 (Totaro et al., 2018, PMID: 30050119). In response to BMP4 stimulation, YAP1 localizes to the nucleus where it represses WNT3 mRNA (Estras et al., 2017, PMID: 29269485), thereby regulating the induction of the three germ layers. Based on these findings, we developed a new mathematical model that integrates tissue mechanics into morphogen dynamics, quantitatively explaining cellular and tissue-scale responses to BMP4 signaling. In all, light induction of the morphogen BMP4 in human embryo models unveiled how embryonic patterning is organized in relation to specific tissue architecture and mechanics at the onset of gastrulation.

overall_design: Opto-BMP4 hESCs were light induced in micropatterns (edge-activated) or in regular culture in absence of geometrical confinment (center-activated) and analyzed 48 hours later by scRNA-seq


title: Manifold roles of CCR7 chemokine GPCR in human trophoblast differentiation

city: St Louis

first: Sabine

last: Dietmann

state: MO

address: 4565 McKinley Avenue

institute: Washington University School of Medicine

summary: CCR7 chemokine G protein-coupled receptor is expressed in extraembryonic tissues of the early human embryo, including trophectoderm and its derivatives cytotrophoblast (CTB), extravillous trophoblast (EVT), and syncytiotrophoblast (STB). However, its function in placental development remains poorly explored. Here, we generated human embryonic stem cells harboring CCR7 deletions and differentiated them into human trophoblast stem cell (hTSC) and hTSC-derived trophoblast organoids. We found that CCR7 mutant EVTs retained hTSC-like characteristics, exhibited decreased epithelial-to-mesenchymal transition, and reduced cell motility. Additionally, CCL21-CCR7 induced EVT terminal differentiation into endovascular EVT-like cells. Transcriptional profiling in CCR7 KO STBs identified reduced viral defense gene expression related to the protection against maternal-fetal transmission. Investigation of trophoblast organoids using single cell transcriptome profiling showed that CCR7 mutant trophoblast organoids comprised a smaller EVT population, but a larger STB population, compared to wild type organoids, while CellChat analysis indicated altered cell-cell communication including WNT, ACTIVIN, and IFN-I signaling pathways. Mechanistically, we found that CCR7 limited the cell-cell fusion of early STB differentiation by reducing cAMP levels. Together, our studies demonstrate that CCR7 plays multiple roles in cellular decision-making during trophoblast differentiation, promoting EVT differentiation, and limiting cell-cell fusion during early STB differentiation.

overall_design: To understand the CCR7 function in trophoblast differentiation and maturation, we generated human trophoblast organoid (hTO) in which all three major trophoblast lineages spontaneously emerge from hTSCs using WT and CCR7 KO hTSCs. By scRNA-seq, we compared their single-cell transcriptome with two biological replicates (n=2).

first: Eun-Ja

last: Yoon

first: Syed

last: Ali

first: Amanda

first: Lilianna

last: Solnica-Krezel


title: Leptosphaeria maculans gene expression during in vitro growth after silencing of DMM1, a gene involved in chromatin remodelling

status: Public on Sep 01 2025

city: Thiverval-Grignon

first: Isabelle

last: Fudal

address: avenue Lucien Bretignieres

country: France

institute: INRA

summary: The transcriptome of Leptosphaeria maculans was analysed in mycelium of the wild type isolate v23.1.3 or in a transformant silenced for DMM1, a gene encoding an enzyme involved in chromatin remodelling. The array probes were designed from gene models from the L. maculans whole genome annotation. The aim of this study was to characterise the effect of chromatin remodelling on gene expression during in vitro growth.

overall_design: We performed 3 hybridizations (NimbleGen) with samples derived from mycelium of a transformant silenced for DMM1 . Three replicates each. All samples were labeled with Cy3.

first: Juliette

last: Linglin


title: Overexpression of miR-200c/141 and miR-200b/200a/429 in MDA-MB-436 cells

city: Guelph

first: Roger

last: Moorehead

address: 50 Stone Rd E

department: Biomedical Sciences

country: Canada

institute: University of Guelph

summary: We previously showed that overexpression of the miR-200c/141 cluster in the TNBC cell line MDA-MB-231 significantly reduced proliferation and invasion in vitro and tumor growth and metastasis in vivo. To confirm the effects of miR-200s in another TNBC cell line, MDA-MB-436 cells were created to overexpress both the miR-200c/141 cluster and the miR-200b/200a/429 cluster.

overall_design: Both the miR-200c/141 cluster and the miR-200b/200a/429 cluster were overxpressed in MDA-MB-436 cells using lentiviral vectors to create MDA-436-200f cells. A control lentiviral vector was used to create MDA-436EV cells


title: Tumour sampling conditions perturb the metabolic landscape of clear cell renal cell carcinoma

city: Cambridge

first: Cissy

last: Yong

state: I am not in the U.S. or Canada

address: Hills Road

department: Surgery

institute: University of Cambridge

summary: Human isotopic tracer studies are fast becoming the gold standard model to study cancer metabolism in vivo. Analysed tissues are typically retrieved after surgical resection, which exposes them to a variable extent of warm ischaemia. Although standardised protocols are emerging, the effects of sampling conditions on the tissue metabolome remain understudied. Here, we perform a 13C-glucose study coupled with metabolomic, transcriptomic, and proteomic profiling in patients with clear cell renal cell carcinoma (ccRCC) to assess the metabolic profile of tissues sampled intraoperatively, when blood supply is intact, versus post-surgical resection, which exposes the tissue to ischaemia. We show that ischaemia significantly affects the metabolic landscape of ccRCC, masking some critical features, such as suppressed gluconeogenesis. Furthermore, in orthotopic ccRCC-derived xenografts, we identified that prolonged exposure to ischaemia disrupts the tissue metabolome stability. Therefore, minimising tissue ischaemia is pivotal in accurately profiling cancer metabolism in these important and resource-intense patient studies.

overall_design: To investigate the impact of ischaemia (induced by tissue sampling conditions) on the molecular characterisation of ccRCC, patient tissues (normal adjacent kidney and ccRCC) were sampled at two timepoints: in vivo (tissues perfused) and post-surgical resection (tissues ischaemic). Each patient, where feasible, underwent multiregional sampling (n= 1-3) of their tumour and kidney. We then performed differential gene expression analysis and gene set enrichment analysis  of RNA-seq data between ccRCC and kidney tissues and between timepoints.

first: Julien

last: Bauer

first: Stephanie

last: Wenlock


title: Novel Bi-Allelic Variants in RINT1 Presenting As Early-Onset Pure Hereditary Spastic Paraplegia

first: Darius

last: Ebrahimi-Fakhari

state: Massachusetts

address: Center for Life Sciences Building CL12160.6

department: Neurobiology

institute: Boston Children's Hospital

summary: The hereditary spastics paraplegias (HSPs) are a group of over 80 neurogenetic disorders that share the feature of progressive lower limb spasticity. Bi-allelic loss-of-function variants in the RINT1 gene have been implicated in acute liver failure in the pediatric population, and were recently described to lead to a complex form of HSP in three children with early-onset spastic paraplegia, ataxia, optic nerve hypoplasia with significant vision impairment, dysmorphic features, and a thin corpus callosum. We read the article by Launay et al. with great interest and would like to add a fourth case due to novel biallelic RINT1 variants presenting with a largely ‘pure’ form of HSP including one missense variant and one splice site variant identifier by whole genome sequencing.

overall_design: To investigate the impact of the splice site variant, we conducted a skin biopsy and created a fibroblast cell line. RNA sequencing was performed.

first: Vicente

last: Quiroz

first: Laura

last: Planas-Serra

first: Abigail

last: Sveden

first: Amy

last: Tam

first: Hyo-Min

last: Kim

first: Umar

last: Zubair

first: Luca

last: Schierbaum

first: Afshin

last: Saffari

first: Maya

last: Chopra

first: Aurora

last: Pujol

first: Erik

last: Eklund


title: Gene expression data from human breast cancer MCF7 cells treated with siRNAs targeting estrogen-inducible long non-coding RNA BNAT1 (breast cancer natural antisense transcript 1)

city: Hidaka

first: Kazuhiro

last: Ikeda

state: Saitama

address: 1397-1 Yamane

country: Japan

institute: Saitama Medical University

summary: Endocrine therapy resistance is a clinical problem for the management of estrogen receptor (ER)-positive breast cancer. The elucidation of factors that modulate ER signaling will provide useful information for understanding the pathophysiology of ER-positive and endocrine-resistant breast cancers. In the screen of estrogen-inducible lncRNAs transcribed from ER alpha-associated active promoters/enhancers, a novel estrogen-inducible lncRNA BNAT1  (breast cancer natural antisense transcript 1), which is transcribed from the proximal promoter region of COL18A1, was identified in ER+ MCF7 cells. siRNA-mediated BNAT1 silencing significantly inhibited the in vitro and in vivo growth of tamoxifen-resistant MCF7 cells.To examine the role of long non-coding RNA BNAT1 (alias gene name COL18AS was used in this dataset) in ER+ breast cancer, MCF7 cells were treated with siRNAs targeting BNAT1 (siCOL18AS, or siBNAT1) or control siRNA (siCtrl, or siControl). The microarray study showed that BNAT1 was closely associated with estrogen signaling pathway.

first: Kuniko

last: Horie

first: Satoshi

last: Inoue


title: Targeting STAT3-FoxO1 axis reverses de novo and acquired PARP inhibitor resistance independent of BRCA status. [Whole-genome seq]

city: Xiamen

first: Qing

last: Li

address: School of Life Sciences, Xiang'an Campus, Xiamen University, Xiang'an District

institute: xiamen university

summary: PARP inhibition has been approved as a compelling strategy for treating multiple human cancers bearing homologous recombination defects (HRD). However, due to the lack of functional biomarkers of PARPi response beyond known genetic mutations in HRD genes, expanding the potential benefit of PARP inhibitors, as well as the identification of effective therapeutic strategies for treating PARPi-resistant cancers remain urgent unmet needs. Here, we report high levels of FoxO1, either at basal expression or upon induction by PARPi, render both BRCA-proficient (BP) and BRCA-deficient (BD) human cancers resistant to PAPRi via modulating transcriptomic signature regulating DNA damage response (DDR). We further elucidated that PARPi-induced STAT3 activation, which occurred through its attenuated dephosphorylation at Y705, resulted in enhanced FoxO1 transcription via recruiting TOP2A, a downstream target of FoxO1. TOP2A orchestrated STAT3-dependent transcriptional program via facilitating RNA Pol II recruitment to gene promoters, as well as promoter-proximal pausing and pause release. Intriguingly, STAT3 inhibitor exhibits a potent synergistic effect with PARPi in treating BP or BD PAPRi-resistant PDX models across cancer types. Our data highlight a potential role of FoxO1 serving as both predictive and prognostic marker for PARPi treatment, and reveal the potency of combination treatment strategy using STAT3 inhibitor with PARPi in sensitizing PARPi-resistant cancers, regardless of BRCA status.

overall_design: Whole genome seq performed in this study was designed to uncover mutations and copy numbers of  patient samples and PDXs.

first: Han

last: You

first: Chen

last: Liu

first: Tong

last: Shu

first: Min

last: Zheng


title: Targeting STAT3-FoxO1 axis reverses de novo and acquired PARP inhibitor resistance independent of BRCA status. [Whole-exome seq2]

overall_design: Whole-exome seq performed in this study was designed to uncover mutations and copy numbers of cell lines, patient samples and PDXs.


title: Targeting STAT3-FoxO1 axis reverses de novo and acquired PARP inhibitor resistance independent of BRCA status [Whole-exome seq]


title: Differential impact of cryopreservation on CD4+ and CD8+ T cell repertoires and clonotypic expansion

city: Baltimore

first: Isha

last: Gurumurthy

state: MD

address: 1650 Orleans Street, CRB1, 4M

department: Oncology

institute: Johns Hopkins University

summary: PBMC cryopreservation is a fundamental technique in immunology research and clinical applications, which is used to assess T cell responses to antigens across disease settings. However, its differential impact on CD4+ and CD8+ T cell repertoire dynamics has not been studied and is of high relevance owing to the increasing number of T cell assays using clonotypic expansions as a functional readout. In this study, we systematically compared the effects of cryopreservation on CD4+ and CD8+ T cell clonotypic expansions using a functional T cell receptor (TCR) sequencing assay. We found that cryopreservation significantly reduces the reproducibility of antigen-specific CD4+ T cell clonotypic expansions compared to CD8+ T cells. The clonality of uncultured CD4+ T cells at baseline was lower than CD8+ T cells, but this alone did not account for the observed differences post-cryopreservation. Our results suggest that freeze-thaw cycles stochastically affect CD4+ T cell clone survival and expansion capacity, leading to inconsistent repertoire changes after antigenic stimulation. These findings have important implications for experimental design and data interpretation in T cell studies, particularly those relying on cryopreserved samples for CD4+ T cell functional assays. We recommend caution when interpreting TCR repertoire data from cryopreserved CD4+ T cell data and suggest using fresh samples where possible for CD4+ T cell studies.

overall_design:
we tested the impact of varying cryopreservation times on the reproducibility of CD8+ and CD4+ T cell expansions within the same donors and against the same classes of antigens in a more controlled and rigorous manner. To adopt a conservative approach, we selected the CEF immunodominant antigenic peptide pool for testing. This decision was based on the rationale that if we could not reproducibly detect responses to these dominant antigens, such effects would likely be amplified with less dominant antigens (i.e. those derived from cancer). After 10 days of culture, we sequenced the TCR Vb CDR3 region to profile the resulting TCR repertoire.

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

middle: N

last: Smith


title: Targeting STAT3-FoxO1 axis reverses de novo and acquired PARP inhibitor resistance independent of BRCA status [ChIP-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: ChIP-seq performed in this study was designed to uncover the role of FoxO1-/STAT3-/TOP2A-mediated regulation of gene transcription.


title: Gene expression profile at single cell level of selected bone marrow from the wild type and the Txnip knock-out mice

city: Shanghai

first: Xiankun

last: Cao

address: Zhizaoju load No.639

department: orthopedic

institute: Shanghai Ninth People's Hospital affiliated to Shanghai Jiao tong University School of Medicine

summary: To investigate the difference in bone remodeling between wild-type and Txnip knock-out mice. we extracted bone marrow from wild-type and Txnip knock-out mice and then screened them to get our interesting cells. We then used single-cell RNA sequencing (scRNA-seq) to analyze the selected bone marrow from wild-type and Txnip knock-out mice.

overall_design: Bone marrow was flushed, sieved, enriched, and finally isolated by Fluorescence-activated cell sorting (FACS) to get specific cells that we were interested and the difference between WT and Txnip-KO was analyzed using scRNAseq.

first: An

last: Qin

first: Jie

last: Zhao


title: A very low carbohydrate, ketogenic diet suppresses tumor insulin signaling and enhances immune infiltration in women with endometrial cancer: results from a randomized feasibility study.

status: Public on Aug 30 2025

first: Ezequiel

middle: Carlos

last: Dantas

state: New York

address: 435 E 30th St

department: Medicine

institute: NYU Langone

summary:
Objectives: To evaluate the feasibility of a very low carbohydrate, ketogenic, diet in women with endometrial cancer and obesity, and to assess the effects of this dietary pattern on metabolism and tumor biology.
Design: A multicentre, parallel, prospective, randomized, controlled feasibility study in treatment naïve women with endometrial cancer. Participants were randomized in a 2:1 fashion to a very-low carbohydrate (VLCD) diet, or to continue with their standard diet (SD) by the method of random permuted block.
Setting: Eight locations from two teaching hospitals in the New York and New Jersey areas.
Participants: 19 treatment naïve women with endometrial cancer (stages IA-IIIC2) and obesity. 15 completed the study.
Intervention: After initial biopsy and pathology confirmation, participants received 21-28 days of VLCD and weekly nutritional counseling, followed by surgical staging.
Main outcome measures: Dietary adherence, rates of attrition, and adverse effects. Changes in circulating concentration of metabolic biomarkers. Changes in immunohistochemical staining and RNA-Sequencing for insulin signaling pathway, cell apoptosis, proliferation, and immunity.
Results: Of the 19 participants randomized, 15 finished the trial with an overall attrition rate of 21%. Participants in the VLCD arm reported consuming 91 ± 4% of the meals, leading to a rise in ketone bodies for all participants by day 3 or 4 and an overall weight loss of 5.5 ± 0.8%. The VLCD was well-tolerated with no grade 3/4 adverse events. Fasting plasma glucose and insulin levels were reduced by 22 ± 5.9% and 60 ± 3.8%, respectively. Total cholesterol and low-density lipoprotein (LDL) were increased by 6 ± 2.7% and 17.8 ± 8.9%, respectively. Gene Set Enrichment Analysis using RNA-Seq revealed enrichment in pathways related to fatty acid oxidation, oxidative phosphorylation, estrogen response, interferon-alpha response and CD8+ T cells (p < 0.05 and NES > 1.60). CD8+ T cells were found to infiltrate the tumor margins under VLCD compared to SD (p = 0.019).
Conclusions: A VLCD is feasible and well-tolerated in obese and overweight women with endometrial cancer and leads to significant host and tumor metabolic changes that suggest potential therapeutic benefits that warrant further investigation in larger clinical trials.

overall_design: We performed a multicentre, parallel, prospective, randomized, controlled, feasibility study in treatment naïve women with endometrial cancer during the presurgical window period between diagnosis and surgical staging. Participants were randomized in a 2:1 fashion to receive a VLCD or to continue with their usual, standard diet (SD) until the day of surgery, 3-4 weeks later.

first: Marcus

last: Goncalves


title: RMRP accelerates ligamentum flavum hypertrophy by regulating GSDMD-mediated pyroptosis through Gli1 SUMOylation

city: nanjing

first: yuanfeng

last: wang

state: jiangsu

address: 101 Longmian Avenue, Jiangning Campus

institute: Nanjing Medical University

summary: Through the RIP experiment, our group found lnc-RMRP was physically associated with Gli1 and exhibited enrichment in Gli1-activated LF cells. Histological studies revealed elevated expression of RMRP in hypertrophic LF. In vitro experiments further confirmed that RMRP promoted Gli1 SUMO modification and nucleus transfer. Mechanistically, RMRP induced GSDMD-mediated pyroptosis, proinflammatory activation, and collagen expression through the Hedgehog pathway. Notably, the mechanical stress-induced hypertrophy of LF in rabbit exhibited analogous pathological changes of LF fibrosis occurred in human and showed enhanced levels of collagen and α-SMA. Knockdown of RMRP resulted in the decreased expression of fibrosis and pyroptosis-related proteins, ultimately ameliorating fibrosis.

overall_design: Sequencing includes two groups, Gli1 overexpressing ligamentum flavum cells group and normal control group, comparing the differentially expressed genes that bind to Gli1 in the two groups

first: Yuanfeng

last: Wang

first: Chao

last: Sun


title: Identification of immunogenic double-stranded RNAs in human cell lines

city: STANFORD

first: Jin

middle: Billy

state: CA

address: 300 Pasteur Dr.

department: Genetics

institute: Stanford University

summary: We expressed different isoforms of ADAR proteins in human cells without A-to-I RNA editing activity to test which isoform(s) was able to rescue the interferon induction phenotypes caused by activation of MDA5 in the absense of double-stranded RNA editing. Using the rescue cells, we sequenced the RNA and profiled RNA editing in order to identify the key RNA editing substrates for MDA5 sensing.

overall_design: Total RNA profiles of wild type (WT) and mutant HEK293 cells expressing different ADAR isoforms/proteins were generated by deep sequencing

first: Tao

first: Qin

first: Hong-Chao

last: Guo

first: Shi-Bin

last: Hu

middle: B


title: SmallRNA seq of leukocytes of chronic pain patients (CRPS, Nerve lesion and Diabetes polyneuropathy) and an SNI mice model ncRNA pain consortium

city: jerusalem

first: hermona

last: soreq

state: -- Select --

address: The Edmond J. Safra Campus, Givat Ram

department: Biological Chemistry

country: Israel

institute: The Hebrew University of Jerusalem

type: Non-coding RNA profiling by high throughput sequencing

summary: Chronic neuropathic pain is widespread, but individual diagnostic biomarkers are unknown and primate specificity hampers rodent validation tests. Here, we report that microRNA (miR)-sequencing of blood leukocytes from 250 multi-centre pain patients revealed complex regional pain syndrome (CRPS)-related increases in the pain-related microRNA (miR)-21-5p and decreases in the cholinergic-targeted miR-335-5p. Both these miRs were similarly modified in dorsal root ganglia of nerve-injured mice, where long RNA-sequencing detected pain-associated elevation of neurogenesis and inflammation-related transcripts. Moreover, either genomic ablation or intrathecal antisense oligonucleotide neuro-suppression of miR-21a-5p, but not genetic debilitation of B7-H1 lymphocytes alleviated murine pain responses while reducing cellular pathways that are induced in patients’ leukocytes; and a cooperative leukocyte ‘signature’ of 12 miRs including miR-21a-5p and -335-5p predicted 96% of CRPS symptoms severity. Our findings implicate cholinergic-suppressible neuro-inflammation processes in chronic acute pain, suggest pathway-based cooperative validation tests and open unprecedented options for mechanistic studies of chronic pain disorders.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: 250 leukocyte samples of chronic pain patients and matching healthy healing/ painless and heathy controls, in addition 3 mice per treatment group of sciatic nerve injured (SNI), SHAM and naïve.

first: Rivka

last: Zangen

first: Michaela

last: Kress

first: Hermona

last: Soreq


title: PGC-1α cooperates with FOXM1 to promote non-small cell lung cancer proliferation via regulating MUC1 expression

city: Dalian

first: Tianyi

last: Zhang

address: No. 9, West Section of Lvshun South Road

institute: The First Affiliated Hospital of Dalian Medical University

summary: To discover the mechanism of PGC-1α affecting the proliferation of NSCLC, high-throughput mRNA sequencing (mRNA-seq)  was performed using the A549 cell lines with overexpression of PGC-1α.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for A549 cells with PGC-1α overexpression or not

first: Zhuoshi

last: Li

first: Chundong

last: Gu


title: The raw data of Ericerus pela single cell sequencing

city: Kunming

last: Lu

address: Bailongsi

institute: Institute of Highland Forest Science, Chinese Academy of Forestry

summary: A single-cell atlas of white wax insect was built to explore the mechanisms that underlie sexual dimorphism in these insects.

overall_design: There are two female samples and two male samples at the different stage were used, they are MP (male pupa), MA (male adult), FN (female nymph) and FA (female adult). The whole body of insects was made into cell suspension and then used for single cell sequencing.

first: Hang

last: Chen

first: Kirst

last: King-Jones

first: Xiaofei

last: Ling


title: Immune factors produced by PBMCs upon stimulation with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1-derived exopolysaccharides inhibit HCoV-229E and SARS-CoV-2 replication

city: Hachioji, Tokyo

first: Shuyi

last: Tang

address: 1-29-1 Nanakuni

department: R&D division

institute: Meiji Co., Ltd.

summary: The COVID-19 pandemic entered a controllable phase due to vaccine and drug development. The development of defense strategies of enhancing host innate immunity remains imperative to counter the emergence of infectious SARS-CoV-2 variants. In this study, we examined the inhibitory effects of Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1)-derived exopolysaccharides (R-1 EPS), a natural immunomodulator, against coronaviral infection. The inhibitory effect of R-1 EPS on HCoV-229E was evaluated first and subsequently extended to SARS-CoV-2. Cell culture supernatant was obtained by stimulating human peripheral blood mononuclear cells with R-1 EPS (R-1 sup), and the inhibitory effect of R-1 sup on coronaviruses was evaluated using the human lung cell line, MRC5. High levels of proinflammatory cytokines were detected in R-1 sup, and replication of both HCoV-229E and SARS-CoV-2 was significantly suppressed in MRC5 cells pretreated with R-1 sup. Transcriptomic analysis revealed that type I IFN signaling was upregulated in R-1 sup-treated MRC5 cells. Our results suggest that immune factors, including proinflammatory cytokines, in R-1 sup, enhance type I IFN response, resulting in a broad spectral inhibitory effect on coronaviruses. This study provides a scientific basis for the application of OLL1073R-1 and R-1 EPS as preventive strategies against SARS-CoV-2 and other coronaviruses.

overall_design: This study investigates the changes in immune response of MRC5 upon treatment with PBMCs supernatant stimulated by R-1 EPS (R-1 sup). Three conditions were compared: untreated control (n=2), R-1 sup treatment (n=5), and untreated PBMCs supernatant (Control sup) treatment (n=5). Samples were collected 24 hours after treatment.

first: Reiko

last: Takai-Todaka

first: Shoko

last: Ishii

first: Hiroki

last: Kono

last: Watanabe

first: Miho

last: Ogawa

first: Hiroshi

last: Kano

first: Kazuhiko

last: Katayama

first: Toshihiro

last: Sashihara

first: Kenichi

last: Hojo

first: Kei

last: Haga


title: scHiCAR: a tri-modal single-cell genomics technology for integrated transcriptome, epigenome, and 3D genome analysis in complex tissues

city: Durham

first: Yarui

last: Diao

state: North Carolina

address: 307 Research Drive

department: Cell Biology

institute: Duke University

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

overall_design: Refer to individual Series


title: The transcriptional repressor AEBP2 is indispensable for the epigenetic control of mimetic thymic epithelial cell differentiation and central self-tolerance induction.

city: Hangzhou

first: Yiyan

last: Zheng

address: Zhiqiang Road 428

institute: Westlake Laboratory of Life Sciences and Biomedicine

summary: Polycomb repressive complex 2 (PRC2) plays a critical role in gene silencing by catalyzing the addition of H3K27me3 marks to chromatin, a modification essential for maintaining developmental gene repression. In thymic epithelial cells (TECs), PRC2 is required for the differentiation and function of medullary TECs (mTECs) but not cortical TECs. This study investigates the role of AEBP2, an accessory subunit of PRC2, in TEC biology, focusing on its impact on thymus development and central tolerance. We demonstrate that AEBP2 is crucial for the maintenance and differentiation of specific TEC subtypes, including microfold TEC, endoTEC, and Tuft cells. Loss of AEBP2 in TECs results in increased thymic cellularity but impairs the expression of tissue-restricted antigens (TRAs) critical for negative selection of thymocytes. The absence of AEBP2 leads to altered chromatin modifications, with changes in H3K27me3 marks at certain specific TRAs’ loci, suggesting a role in the epigenetic regulation of TRA expression. Furthermore, the loss of AEBP2 correlates with a greater risk of autoimmunity, as evidenced by increased T and B lymphocyte infiltration in peripheral organs. These findings highlight the essential role of AEBP2 in regulating TEC differentiation and self-antigen presentation, providing new insights into the molecular mechanisms of central T cell tolerance.

overall_design: 1500 cTECs (EpCAM+Ly51+) and 1500 mTECs (EpCAM+UEA1+) are sorted from the conventional E18.5 Aebp2-/- embryos, subjected for bulk RNAseq. 10,000 total EpCAM+ cells and 12,000 total EpCAM+ cells were sorted from both Aebp2-flox and Aebp2-ko groups, each of which is pooled of three 6-8 weeks old female mice of the same genotype for scRNAseq and scATACseq, respectivly. There are two experimental replicates from both Aebp2-flox and Aebp2-ko groups for both the scRNAseq and scATACseq. For the cut-tag experiment, 15,000 MHCIIhi mTECs were sorted from both Aebp2-flox and Aebp2-ko 6-8 weeks old female mice.

first: Wei

last: Wu

first: Georg

last: Hollander


title: Coordinated microRNA/mRNA expression profiles reveals unique skin color regulatory mechanisms in Chinese giant salamander (Andrias davidianus)

city: Luoyang

first: Yanjie

last: Guo

state: Henan

address: 6# jiqing road

institute: Luoyang normal university

summary: To investigate the molecular mechanisms of skin pigmentation in Andrias davidianus, we performed gene expression profiling analysis using data obtained from RNA-seq of skin samples from 2 different wild type Andrias davidianus and 2 different albino type Andrias davidianus.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for wild type and albino type Andrias davidianus.

first: Weini

first: Yaowu

last: Zhang

first: Xueyi

last: Yang


title: scHiCAR: a tri-modal single-cell genomics technology for integrated transcriptome, epigenome, and 3D genome analysis in complex tissues [cellline_scHiCAR]

summary: The three-dimensional (3D) organization of cis-regulatory elements (CREs) plays a central role in transcription control. However, capturing transcriptome, epigenome, and 3D genome from the same single cells remains technically challenging. Here, we present scHiCAR (single-cell Hi-C with ATAC and RNA-seq), a combinatorial barcoding-based method that simultaneously profiles mRNA, open chromatin, and chromosome-conformation-capture from the same cells. Compared to existing single-cell 3D genome methods, scHiCAR more efficiently enriches long-range cis-interactions anchored at candidate CREs (cCREs). Applied to 1.62 million mouse brain cells and complemented with a deep learning-based loop caller, scHiCAR accurately defines cell-type-specific transcriptomes, accessible cCREs, and 5kb-resolution enhancer-promoter pairs across 22 brain cell types. scHiCAR also performs robustly in challenging tissues such as skeletal muscle, enabling tri-modal single-cell level analysis of gene regulation dynamics during muscle stem cell regeneration. scHiCAR offers a scalable, efficient, and cost-effective platform for studying gene regulatory landscapes in complex tissues at single-cell resolution.

overall_design: We developed a new method, scHiCAR, which enables high-throughput detection of the transcriptome, epigenome, and 3D genome at single-cell resolution. We validated its performance in three cell lines: human H1 and GM12878, and mouse embryonic stem cells (mESCs).

first: Xiaolin

last: Wei

first: Yueyuan

last: Xu

first: Dongchan


title: Plasma-treated water applied as a foliar spray promotes root growth in barley

status: Public on Aug 29 2025

city: Greifswald

first: Stefan

last: Simm

address: Walter-Rathenau-Straße 48

department: Bioinformatics

country: Germany

institute: University Medicine Greifswald

summary: Plasma-treated water (PTW) contains reactive oxygen and nitrogen species and can therefore induce mild oxidative stress in plants. In a previous study, PTW treatment of leaves resulted in both short- and long-term systemic signals. RNA-seq was applied to analyse the adaptive response triggered by PTW treatment and to further determine the mode of action of PTW in barley leaves and roots under short- and long-term conditions. The application of PTW to the leaves resulted in stronger long-term transcriptional changes in the roots. PTW treatment significantly increased root biomass, while it had no effect on shoot growth. In roots the signalling of auxin, ethylene, brassinosteroids and gibberellin was stimulated, while cytokinin signalling was impeded. Many genes encoding cell wall modifying enzymes, structural proteins and receptor kinases were upregulated in the roots in long-term response to PTW. This indicates that PTW treatment appears to affect root growth by promoting cell elongation. In addition, foliar treatment with PTW led to changes in root architecture: root length, surface area, diameter and number of forks increased in the long term, as did the content of soluble phenolic compounds. All these changes indicate that PTW could be a suitable stimulant for improving the root growth of plants.

overall_design: To investigate the priming effect of plasma-treated water (PTW) as a leaf-spray on barley, plants were harvested 1 day or 4 weeks after PTW or control (sprayed with deionized water) treatment. RNA was extracted from leaf and root samples (each pooled from 5 plants) for RNA-seq. Gene expression profiling was performed for 2 treatments (control & PTW) at 2 timepoints in both organs.

first: Krüger

last: Andrea

first: Schlömer

last: Stefan

first: Simm

first: Bold

last: Jessica

first: Stöhr

last: Christine


title: Targeting STAT3-FoxO1 axis reverses de novo and acquired PARP inhibitor resistance independent of BRCA status

first: Qing

last: Li


title: Human Brain Cell-Type-Specific Aging Clocks Based on Single-Nuclei Transcriptomics

city: Budapest

first: Karolina

last: Pircs

address: Tűzoltó street 37-47

department: Institute of Translational Medicine

country: Hungary

institute: Semmelweis University

summary: Aging is the primary risk factor for most neurodegenerative diseases, yet the cell-type-specific progression of brain aging remains poorly understood. Here, human cell-type-specific transcriptomic aging clocks are developed using high-quality single-nucleus RNA sequencing data from post mortem human prefrontal cortex tissue of 31 donors aged 18–94 years, encompassing 73,941 high-quality nuclei. Distinct transcriptomic changes are observed across major cell types, including upregulation of inflammatory response genes in microglia from older samples. Aging clocks trained on each major cell type accurately predict chronological age, capture biologically relevant pathways, and remain robust in independent single-nucleus RNA-sequencing datasets, underscoring their broad applicability. Notably, cell-type-specific age acceleration is identified in individuals with Alzheimer's disease and schizophrenia, suggesting altered aging trajectories in these conditions. These findings demonstrate the feasibility of cell-type-specific transcriptomic clocks to measure biological aging in the human brain and highlight potential mechanisms of selective vulnerability in neurodegenerative diseases.

overall_design: To develop cell-type specific transcriptomic aging clocks for the human prefrontal cortex, we perfomed single-nuclei RNA sequencing on frozen post mortem brain tissue derived from 31 subjects between 18 and 94 years of age at the time of death with median post mortem interval (PMI) of 4.5 (2-12) hours, across three age groups of human adulthood. The frozen samples were collected from the lateral surface of the prefrontal cortex, namely, the ventrolateral prefrontal cortex, the dorsolateral prefrontal cortex and the middle frontal gyrus, followed by nuclei isolation using ultracentrifugation and FACS sorting, before performing snRNAseq using 10X genomics (see Methods section for further details).

first: Chandramouli

last: Muralidharan

first: Enikő

last: Zakar-Polyák

first: Anita

last: Adami

first: Anna

last: Abbas

first: Yogita

last: Sharma

first: Raquel

last: Garza

first: Jenny

middle: G

last: Johansson

first: Diahann

last: Atacho

first: Éva

last: Renner

first: Miklós

last: Palkovits

first: Csaba

last: Kerepesi

first: Johan

last: Jakobsson


title: Autoimmune Disease Risk Gene ANKRD55 Promotes Th17 Effector Function Through Metabolic Modulation [RNA-Seq]

status: Public on Aug 28 2025

city: CAMBRIDGE

first: Jacques

last: Deguine

address: 415 Main Street, 415M-7175 - Xavier lab

department: Immunology Program

institute: Broad Institute

summary: Genome-wide association studies (GWAS) have linked the locus encoding Ankyrin Repeat Domain 55 (ANKRD55) with numerous autoimmune diseases; however, its biological function and role in inflammation are unclear. Here, we demonstrate that Ankrd55-deficient mice are protected from T cell-mediated colitis but are more susceptible to Citrobacter rodentium infection. Mechanistically, Ankrd55 deletion impairs CD4+ T cell proliferation and reduces effector cytokine production in T helper 17 (TH17) cells in a cell-intrinsic manner. ANKRD55 is associated with mitochondria, and its loss is associated with impaired mitochondrial respiration and activation of the LKB1 pathway. Consistently, IL-17 production can be rescued by the deletion of LKB1 in Ankrd55-deficient T cells. Altogether, our study implicates the protein ANKRD55 as a functional modulator of T cell metabolism that directly impacts TH17 responses, highlighting it as a potential target across multiple autoimmune diseases.

overall_design: T cells were harvested from wild-type or Ankrd55-deficient animals and differentiated in vitro towards different helper phenotypes. Bulk RNA sequencing was performed at the end of the differentiation process using 3 independent animals and 2 technical replicates (cells from the same animal plated in different wells) for each condition.

first: Kjinjin

last: Xu

first: Lingjia

last: Kong

first: Elizabeth

last: Creasey

first: Sneha

last: Rath

first: Lei

last: Deng

first: Julian

last: Avila-Pacheco

first: Chenhao

first: Blayne

last: Oliver

first: Tyler

last: Dao

first: Angela

middle: R

last: Shih

first: Mark

last: Daly

first: Alex

last: Shalek

first: Clary

last: Clish

first: Daniel

last: Graham

first: Ramnik

last: Xavier


title: Autoimmune Disease Risk Gene ANKRD55 Promotes Th17 Effector Function Through Metabolic Modulation [ATAC-Seq]

overall_design: T cells were harvested from wild-type or Ankrd55-deficient animals and differentiated in vitro towards different helper phenotypes. Bulk ATAC sequencing was performed at the end of the differentiation process.

last: Li


title: Genome-wide maps of ICN1, PRC1  and NuRD subunits and H3K27me3 upon DMSO or gamma secretase inhibition (GSI) conditions in SupT1 cells.

city: Toulouse

first: Olivier

last: Cuvier

address: 118 route de Narbonne

department: LBME

institute: CNRS

summary: we used the technnology of ChIP-sequencing to sepcifically analyze the recruitment of the Notch Repressive Complex onto Notch-target genes.

overall_design: SupT1 T-ALLL were treated for 2 days with DMSO or GSI and the different factors of the Notch repressive Complex were ChIPed

first: Cécile

middle: M

last: Doyen

first: David

last: Depierre

first: Monsef

last: Benkirane


title: RNA-Seq analysis after overexpression of AtmiR165a in Arabidopsis Shoot Apical Meristem in clv3 mutant background

city: Mohali

first: Hasthi

last: Ram

address: Sector 81

department: Agriculture biotechnology

country: India

institute: NABI (National Agri-Food Biotechnology Institute)

summary: Results from experiments done on knock-down of adaxial class III HD ZIP genes, using overexpression of miR165a, in clv3 shoot meristem show that Class III HD-ZIP genes act generally to repress the formation of new growth axes where they are expressed. This study explored the genes directly regualted by miRNAs as well as indirectly regulated by class III HD-ZIPs.

overall_design: Comparative gene expression profiling analysis of RNA-seq data arabidopsis SAM of clv3l mutant plants and ap1cal mutant plants expressing AtmiR165a under the Ubiquitin10 promoter.

first: Marcus

last: Heisler


title: RNA-Seq analysis after overexpression of AtmiR165a in Arabidopsis Shoot Apical Meristem

summary: Results from experiments done on knock-down of adaxial class III HD ZIP genes, using overexpression of miR165a, in shoot meristem show that Class III HD-ZIP genes act generally to repress the formation of new growth axes where they are expressed. This study explored the genes directly regualted by miRNAs as well as indirectly regulated by class III HD-ZIPs.

overall_design: Comparative gene expression profiling analysis of RNA-seq data arabidopsis SAM of ap1cal mutant plants and ap1cal mutant plants expressing AtmiR165a under the Ubiquitin10 promoter.


title: Expression data from type 2 diabetes mellitus adipose-derived stem cells cultured with basic fibroblast growth factor

status: Public on Aug 27 2025

city: Barcelona

first: Gemma

last: Arderiu

address: Avda. S. Antoni M. Claret 167

department: Cardiovascular area

country: Spain

institute: Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau IIB-Sant Pau

summary:
Diabetes affects ASCs characteristics such as: proliferation, differentiation and angiogenic capacity. MicroRNAs are able to target genes involved in vascular remodeling and promote or inhibit structural changes in the vessel wall. Adipose tissue-derived stem cells (ASCs) have the capacity to contribute to vascular remodeling.
We used microarrays to detail the global miRNA expression profile underlying cell differentiation and identified distinct classes of up-regulated and down-regulated genes during this process.

overall_design: Human ASCs from white AT were obtained by surgical procedures from type 2 diabetes mellitus patients. ASCs from fat depots type 2 diabetes mellitus subjects were induced to differentiate into ECs. The expression of 2025 pre-miRNAs and 2578 mature miRNAs was assessed.

first: Lina

last: Badimon

first: Anna

last: Civit

first: Sandra

last: Camino-López

first: Olaya

last: García


title: Tumour genotype shapes blood biomarker expression for use in pancreatic cancer detection and diagnosis [Tumour]

city: Edinburgh

first: Alan

last: Serrels

address: Crewe Road South

department: Institute of Genetics and Cancer

institute: University of Edinburgh

summary: Typically diagnosed late, when systemic metastasis has already occurred, pancreatic ductal adenocarcinoma (PDAC) has one of the worst 5-year survival rates of any cancer type. For many patients with advanced disease, current chemotherapy regimens offer only modest benefit despite significant toxicity and surgical resection, the only treatment option with curative potential, is not possible. Therefore, while new treatments are much needed, diagnosing patients at an ‘earlier’ disease stage when surgery remains possible and the window of opportunity for treatment response is longer will be critical to improving patient outcomes. In this regard, the identification of biomarkers from biospecimens that can be easily sampled from patients remains the focus of considerable research, however success has not been forthcoming. Using a suite of novel genetically defined murine isogenic models of early PDAC, engineered using CRISPR-Cas9 gene editing, we sought to address whether loss-of-function mutations in common driver genes, and thus the genetic heterogeneity inherent to the disease, may represent an important confounding factor in the identification of a one-size-fits-all biomarker suitable for early detection. Focussing on the multi-omics analysis of blood, we show that both loss of Cdkn2a and / or Smad4 on the background of a KrasG12D Trp53-/- genotype has profound effects on the profile of differentially expressed RNA species including protein coding RNAs, lncRNAs, snoRNAs, scRNAs, snRNAs and miRNAs, and on plasma protein expression, when compared to both healthy controls and chemically induced pancreatitis. In addition, we find that loss of Smad4, a genomic event that occurs following progression from PanIN to PDAC, substantially limits the availability of blood biomarkers. These findings identify the need to move towards genotype-specific biomarker signatures and uncover a potential role for Smad4 loss in limiting opportunities for the early detection of pancreatic cancer.

overall_design: To investigate the impact of common driver gene loss-of-function on blood biomarker expression we isolated RNA from whole blood from mice harbouring pancreatic tumours established from cell lines engineered to model different genetic backgrounds common to human pancreatic cancer.

first: Marta

last: Canel


title: scHiCAR: a tri-modal single-cell genomics technology for integrated transcriptome, epigenome, and 3D genome analysis in complex tissues [mouse_skeletal_muscle_scHiCAR]

first: Yarui

last: Diao

overall_design: We developed a new method, scHiCAR, which enables high-throughput detection of the transcriptome, epigenome, and 3D genome at single-cell resolution. We performed scHiCAR on adult mouse skeletal muscle in three conditions: uninjured, and at 5 and 7 days following BaCl₂-induced acute injury.

first: Xiaolin

last: Wei

first: Yueyuan

last: Xu

first: Dongchan

last: Yang


title: Systemic inflammation–induced adipose tissue remodeling drives psoriasis exacerbation in obesity through epigenetic and immunometabolic dysregulation

city: Incheon

first: Mijoo

last: Ahn

state: Yeonsu-gu

address: 155 Gaetbeol-ro

country: South Korea

institute: Gachon University

summary: Obesity is a risk factor for psoriasis and negatively influences the severity, treatment responsiveness, and systemic comorbidities of psoriasis. This study aimed to investigate comprehensive inflammatory changes in obesity-associated psoriasis using an obese mouse model of psoriasis induced by topical application of imiquimod or dermal injection of interleukin (IL)-23. Obese mice exhibited aggravated psoriatic dermatitis with pronounced systemic inflammatory responses when exposed to imiquimod. Notably, imiquimod-induced psoriatic dermatitis in obese mice significantly reduced fat mass. Further, pronounced monocyte–macrophage infiltration of perigonadal adipose tissue, increased expression of genes linked to inflammation, and upregulation of cell death-associated molecules were evident in obese mice treated with imiquimod compared with their lean counterparts. In contrast, IL-23 injection could induce similar features of psoriatic inflammation in obese and lean mice, without causing adipose tissue destruction or a systemic increase in inflammatory mediators. Obese adipose tissue of mice with imiquimod-induced psoriatic inflammation features genetic and epigenetic changes in adipocytes and shifts in macrophage compartments toward disturbed homeostasis using multiomic single-nucleus sequencing targeting RNA and accessible chromatin. Therefore, systemic manifestations of psoriasis, coupled with obesity-induced changes in adipose tissue, synergistically exacerbate psoriasis by disrupting the homeostatic microenvironments of adipose tissue.

overall_design: Adipose tissues of mice with imiquimod-induced and IL-23-induced psoriasis were analyzed using multiomic single-nucleus sequencing.

first: YunJae

last: Jung

first: HeeJoo

last: Kim

first: IkSoo


title: RSS mediated persulfidation cascade regulation mechanism of novel transcription factor SscRAc in extremophile Acidithiobacillus caldus under extreme copper stress

city: Wuxi

first: Xingyu

last: Huo

state: Jiangsu

address: No. 1800, Lihu Avenue

institute: Jiangnan University

summary: Biomining microorganisms are classified as extremophiles due to their chronic exposure to elevated metal ion concentrations, which drives evolutionary adaptations for environmental stress resistance. This study investigates the copper tolerance mechanisms in Acidithiobacillus caldus CCTCC M 2018727, a strain demonstrating exceptional metal resistance through long-term adaptive laboratory evolution (survival at 250 mM Cu²⁺). Comparative analysis revealed a 350.6% increase in intracellular reactive sulfur species (RSS) levels under 250 mM Cu²⁺ stress. Sulfur-related post-translational modification proteomics demonstrated system-wide persulfidation enhancement and identified SscRAc, a novel RSS-sensitive MarR family transcription factor. Genetic deletion of sscRAc increased copper susceptibility and disrupted cellular redox homeostasis. Chromatin immunoprecipitation and qRT-PCR analyses revealed SscRAc’s dual regulatory mechanism: suppressing copper efflux systems while activating RSS metabolic pathways to maintain intracellular equilibrium. LC-MS/MS analysis revealed that both Cys74 and Cys78 in SscRAc interact with RSS and undergo persulfidation, resulting in the dissociation of the protein from the promoter-DNA of target genes. Furthermore, upstream signaling analysis uncovered a reciprocal regulatory relationship between SscRAc and the copper-sensitive transcription factor CsoRAc, establishing a coordinated copper-RSS signaling network. This work identifies SscRAc as a pivotal regulator of copper tolerance in A. caldus and delineates a novel metal stress response pathway connecting copper toxicity with sulfur redox biochemistry.

overall_design: ChIP-seq profiling of SscRAc transcription factor binding sites in Acidithiobacillus caldus strain CCTCC M 2018727. Constructed recombinant plasmid p-sscRAc-Flag expressing 3×Flag-tagged SscRAc, which was transformed into donor strain E. coli SM10. The A. caldus p-sscRAc-Flag strain was subsequently generated via conjugation transfer.

first: Huo

last: Xingyu

first: Tong

last: Yanjun

first: Yang

last: Haililn

first: Feng

last: Shoushuai


title: GFAT1 promotes the progression of hepatocellular carcinoma via enhancing the O-GlcNAcylation of VEZF1

status: Public on Aug 26 2025

city: 重庆

middle: jia

last: yao

address: Medical College Road

department: Key Laboratory of Molecular Biology for Infectious Diseases

institute: Chongqing Medical University

summary: Glutamine-fructose-6-phosphate amidotransferase 1 (GFAT1), the first rate-limiting enzyme in the hexosamine biosynthetic pathway (HBP), is a key factor controlling HBP flux. However, the molecular mechanism underlying the roles of GFAT1 in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we found that GFAT1 was upregulated in HCC, and high GFAT1 level was correlated with poor patient prognosis. Our in vitro and in vivo studies demonstrated that GFAT1 facilitated hepatoma cell proliferation and invasion by enhancing HBP and O-GlcNAcylation through its enzymatic activity. Global profiling of O-GlcNAcylation identified vascular endothelial zinc finger protein 1 (VEZF1) as a substrate heavily O-GlcNAcylated in GFAT1-overexpressing hepatoma cells. Notably, O-GlcNAcylation at specific serine residues (Ser123 and Ser124) within VEZF1 attenuated its proteasomal degradation, thereby enhancing its protein stability and promoting tensin 1 (TNS1) transcription in HCC. In addition, we designed a bioactive VEZF1-derived peptide to competitively inhibit GFAT1-mediated O-GlcNAcylation of VEZF1. This intervention effectively reduced TNS1 expression and suppressed the progression of HCC in a mouse model. Together, these findings highlight the therapeutic potential of targeting the GFAT1-VEZF1-TNS1 signaling axis in HCC.

overall_design: we used lentivirus-encoded sgRNA to eliminate endogenous VEZF1 in HepG2 cells followed by re-expression of VEZF1WT or VEZF12A.ChIP-seq was performed.

first: Jia-yao

first: Rong

last: Zhang


title: scHiCAR: a tri-modal single-cell genomics technology for integrated transcriptome, epigenome, and 3D genome analysis in complex tissue [mouse_brain_bulk_HiCAR]

overall_design: We developed a new method, scHiCAR, which enables high-throughput detection of the transcriptome, epigenome, and 3D genome at single-cell resolution. To validate scHiCAR-derived chromatin and 3D genome profiles, we generated bulk HiCAR data from FACS-isolated astrocytes and Pvalb neurons derived from lineage-traced mouse brain.


title: Claudin-1 contributes to gastrointestinal stromal tumors (GIST) resistance to imatinib mesylate (IM) via regulation of FGFR2-mediated signaling.

city: Tokyo

first: Ruslan

last: Deviatiiarov

address: Hongo 2-1-1, Bunkyo-ku

department: Intractable Disease Research Center

institute: Juntendo University

summary: Acquired resistance of gastrointestinal stromal tumors (GISTs) to imatinib mesylate (IM) is one of the most critical challenges in GIST therapy. Here we show that a long-term culture of GIST T-1 cells with IM induces clonal heterogeneity resulting in the appearance of cancer cells exhibiting activation of the FGFR-signaling pathway which was associated with KIT loss. The first one was due to the overexpression of FGFR1/2 and increased production of FGF-2 ligand. These events maintained GIST resistance to IM and rendered these GIST cells highly sensitive to all types of pan-FGFR-inhibitors used in the current study. Knockout of FGFR2 in this GIST subclone significantly attenuated pro-apoptotic and anti-proliferative activities of infigratinib (BGJ 398) both in vitro and in vivo, thereby suggesting the activation of FGFR-signaling pathway via FGFR2-mediated axis as the predominant molecular mechanism in these GIST cells. Collectively, the extended inhibition of KIT-signaling in GISTs induces clonal heterogeneity of cancer cells and might change the tumor’s sensitivity to FGFR-inhibitors due to selection of cancer cells with an FGFR-overactivated pathway.

overall_design: Resistance to the targeted therapy in GIST is a significant limitation of treatment efficacy.  This study aimed to examine the role of claudin 1 (CLDN1) in GIST resistance to imatinib mesylate (IM). To examine the molecular mechanisms involved in CLDN1-mediated resistance of GIST to IM, we initially performed transcriptome profiling of IM-resistant GIST-T1 (GIST-T1R) cells transfected with siCLDN1 or treated with PDS-0330.

first: Sergei

last: Boichuk

first: Elena

last: Shagimardanova


title: Human memory CD4+ T cells recognize Mycobacterium tuberculosis-infected macrophages amid broader pathogen-specific responses [scRNA-seq]

status: Public on Aug 25 2025

city: Cleveland

first: Robert

last: Schauner

state: Ohio

address: 10900 Euclid Ave

department: Division of Infectious Diseases and HIV Medicine

institute: Case Western Reserve University

summary: CD4+ T cell-mediated control of tuberculosis (TB) requires recognition of macrophages infected with Mycobacterium tuberculosis (Mtb). Yet not all Mtb-specific T cells recognize infected macrophages. Using infected monocyte-derived macrophages (MDMs) and autologous memory CD4+ T cells from individuals with latent Mtb infection (LTBI), we isolate and quantify CD4+ T cells activated in response to infected macrophages. We use T cell antigen receptor (TCR) sequencing to determine the total and unique Mtb-specific TCR clonotypes linked to recognition of infected macrophages, and find that a subset required exogenous antigen exposure, suggesting incomplete recognition. Clonotypes specific for multiple Mtb antigens, and other pathogens, were also identified. We use bulk TCRb deep sequencing from total CD4+ T cells isolated from 10x106 PBMCs from each participant to determine the natural circulating frequencies of relevant TCR clonotypes. We used single-cell RNA sequencing (scRNAseq) to examine the effector functions of CD4+ T cells in response to infected macrophages. Mtb-specific clonotypes expressed signature effector functions dominated by IFNg, TNF, IL-2, and GM-CSF or chemokine production and signaling. We propose TB vaccines that elicit T cells specific for T7SS substrates, recognize infected macrophages, and express canonical effector functions will offer protection against TB.

overall_design: CD4+ T cells from donors with or without latent tubucrulosis infection (LTBI) were stimulated with Mtb-infected macrophages with or without Mtb lysate. Activated T-cell (CD4+CD69+CD40L+) were sorted by FACS prior to library prepratation.

first: Stephen

last: Carpenter

first: Daniel

last: Gail


title: GFAT1 promotes the progression of hepatocellular carcinoma via enhancing the O-GlcNAcylation of VEZF1 [RNA-seq]

first: Jiayao

last: Yang


title: Transcriptome sequencing screening mRNA

city: zhengzhou

first: Deqian

last: Kong

state: henan

address: No.1 Longhu Zhonghuan Road, Jinshui District

institute: The First Affiliated Hospital of Zhengzhou University

summary: Oxidative stress plays a pivotal role in age-related diseases, including oxidative aging, by promoting cellular damage and dysfunction.

overall_design: In this study, we performed transcriptome sequencing to identify mRNA markers and pathways associated with oxidative aging in human lens epithelial cells (LECs). Through bioinformatics analysis, key mRNAs involved in oxidative stress response, mitochondrial dysfunction, and aging were significantly altered.

first: Dq


title: BMP4 and BMP6 stimulation of adult mouse muscle stem cells activates the Notch signaling pathway

city: Berlin

first: Markus

last: Schuelke

state: Berlin

address: Augustenburger Platz 1

department: Neuropediatrics

institute: Charite

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

overall_design: Refer to individual Series


title: A CRISPR-Activation CROP-seq Screen Identifies HMGN1 as a Dosage Sensitive Regulator of Heart Defects in Down Syndrome (scRNA-Seq)

city: San Francisco

first: Angelo

last: Pelonero

address: 1650 Owens Street

department: Cardiovascular Disease Institute

institute: Gladstone Institutes (UCSF)

summary: Congenital heart defects (CHD) are the most common form of developmental abnormalities, occurring in ~1% of live births, and can arise due to altered dosage of genes essential for cardiogenesis. Aneuploidy accounts for nearly 15% of CHD and the most frequent form involves trisomy of chromosome 21 (Ch21), resulting in Down Syndrome (DS). Here we used single cell RNA-seq, CRISPR-activation with single cell RNA-seq, single cell ATAC-seq and Cut&Tag epigenomic profiling to define the molecular disruptions occuring with Trisomy 21 and upregulation of the Ch21 epigenetic factor HMGN1. These experiments were performed in human pluripotent stem cells (hiPSCs) or in directed differentiation to cardiomyocyte lineages at days 10 and 20.

overall_design: We used human pluripotent stem cells (hIPSCs) from an individual who was mosaic for Down Syndrome. Thus we compare cells that are trisomic for Ch21 with cells that are isogenically similar and disomic for Ch21. As well, we generated a CRISPR-activation knock-in to disomic cells and used sgRNAs directed to chromosome 21 genes. Sample replicates are defined and all single cell samples were processed with 10X Genomics pipelines. Cut&Tag samples were processed with Epicypher reagents. All samples were isolated with Accutase or Trypsin reagents.

first: Sanjeev

last: Ranade

first: Deepak

last: Srivastava


title: A CDK11-dependent RNA polymerase II pause-release checkpoint precedes CDK9-mediated transition to transcriptional elongation [ChIP-Seq]

city: Melbourne

first: Jennifer

middle: Rose

last: Devlin

state: Victoria

address: Peter MacCallum Cancer Centre, 300 Grattan Street

department: The Sir Peter MacCallum Department of Oncology at Peter MacCallum Cancer Centre

country: Australia

institute: University of Melbourne

summary: Controlled gene expression is achieved through the intricate regulation of RNA polymerase II (Pol II) progression through transcription-cycle checkpoints. The pausing checkpoint, where Pol II temporarily stalls prior to release into transcriptional elongation, is a key molecular mechanism that fine-tunes gene expression. While the critical contribution of cyclin-dependent-kinase 9 (CDK9) for Pol II pause-release is well established, the requirement for other CDKs has not been fully elucidated. Here we identify a new role for CDK11 in the Pol II pausing-to-elongation transition at a checkpoint that is distinct and independent from CDK9. Selective CDK11 inhibition results in genome-wide stalling of Pol II at transcription-start-site (TSS) proximal regions and acute RNA synthesis ablation near the beginning of transcriptional units. High-resolution chromatin-immunoprecipitation and precision-nuclear-run-on assays reveals spatial differences between CDK11- and CDK9-dependent Pol II pause sites, with CDK11 regulating Pol II closer to the TSS. Cancer cells exhibit profound reliance on functional CDK11, with selective CDK11 inhibition providing therapeutic efficacy in pre-clinical in vivo models of leukaemia and lymphoma, demonstrating the importance of CDK11-dependent Pol II regulation for aggressive haematological malignancies.

overall_design: To investigate the role of CDK11 for Pol II chromatin binding genome wide, human AML cells were treated with CDK11 inhibitor or had CDK11 protein depleted. Cells were treated with a CDK9 inhibitor as a comparator.


title: A CDK11-dependent RNA polymerase II pause-release checkpoint precedes CDK9-mediated transition to transcriptional elongation [RNA-seq]

overall_design: To investigate the role of CDK11 for nascent RNA production, steady-state gene expression, and acute transcriptional activation, human AML cells were treated with CDK11 inhibitor or had CDK11 protein depleted.


title: A CDK11-dependent RNA polymerase II pause-release checkpoint precedes CDK9-mediated transition to transcriptional elongation [PRO-seq and TT-seq]

overall_design: To investigate the role of CDK11 for Pol II transcriptional activity human AML cells were treated with CDK11 or CDK9 inhibitors, either at steady-state or following synchronisation with DRB, and precision-nuclear-run on experiments were performed.


title: Single-cell RNA sequencing reveals different cellular states in malignant cells and the tumor microenvironment in primary and metastatic ER-positive breast cancer

status: Public on Aug 22 2025

city: Portland

first: FURKAN

last: OZMEN

state: OR

address: 2720 S Moody Ave, Portland, OR 97201,USA

department: Division of Oncological Sciences

institute: Oregon Health & Science University

summary: Metastatic breast cancer remains largely incurable, and the mechanisms driving the transition from primary to metastatic breast cancer remain elusive. We analyzed the complex landscape of estrogen receptor (ER)-positive breast cancer primary and metastatic tumors using scRNA-seq data from twenty-three female patients with either primary or metastatic disease. By employing single-cell transcriptional profiling of unpaired patient samples, we sought to elucidate the genetic and molecular mechanisms underlying changes in the metastatic tumor ecosystem. We identified specific subtypes of stromal and immune cells critical to forming a pro-tumor microenvironment in metastatic lesions, including CCL2+ macrophages, exhausted cytotoxic T cells, and FOXP3+ regulatory T cells. Analysis of cell-cell communication highlights a marked decrease in tumor-immune cell interactions in metastatic tissues, likely contributing to an immunosuppressive microenvironment. In contrast, primary breast cancer samples displayed increased activation of the TNF-α signaling pathway via NF-kB, indicating a potential therapeutic target. Our study comprehensively characterizes the transcriptional landscape encompassing primary and metastatic breast cancer.

overall_design: We used single-cell RNA sequencing (scRNA-seq) to investigate mechanisms driving the transition from primary to metastatic breast cancer. Tumor samples were collected from 23 patients diagnosed with either primary or metastatic breast cancer. Tumor tissues were dissociated into single-cell suspensions. Single-cell RNA libraries were then prepared and sequenced.

first: Furkan

last: Ozmen

first: Tugba

last: Yildiran Ozmen

first: Aysegul

last: Ors

first: Gordon

last: Mohammed

first: Hisham


title: c-Myc Inhibits Macrophage Antimycobacterial Response in Mycobacterium tuberculosis Infection

city: Zürich

first: Johannes

last: Nemeth

address: Rämistrasse 100

department: Department of Infectious Diseases and Hospital Epidemiology

country: Switzerland

institute: University Hospital Zurich

summary: Mycobacterium tuberculosis (MTB) is a major global cause of mortality, responsible for over a million deaths each year. Despite this burden, natural immunity prevents disease in more than 90% of exposed individuals. Previous studies have identified interferon-gamma (IFN-γ) as a key regulator of innate immune defense against MTB. Here, we investigate the impact of IFN-γ timing on macrophage-mediated control of MTB infection. We demonstrate that IFN-γ exposure before infection enhances macrophage antibacterial activity, whereas post-infection exposure does not. Further analysis of this phenotype revealed a strong association between c-Myc signaling and macrophage function in MTB control, as identified through unbiased in vitro systems approaches. Given the difficulty of perturbing c-Myc in primary cells, we developed a lentiviral system for c-Myc inhibition and overexpression. We profiled both datasets (IFN-γ timing and c-Myc inhibition) to characterize the resulting transcriptional shifts.

overall_design: IFN-γ timing experiments: BMDMs were isolated and differentiated as described in the Methods section. BMDMs that differentiated for 6 days were stimulated with IFN-γ according to the following conditions and were infected with MTB: full treatment (C3), IFN-γ only before MTB infection (C1), IFN-γ only after MTB infection (C2) and no IFN-γ treatment (C4). RNA was extracted after 6 and 24 hours. c-Myc inhibition experiments: HSCs and immune progenitors were isolated, transduced and differentiated as described in the Methods section. Transduced and WT BMDMs received doxycycline to induce overexpression c-Myc or Omomyc (c-Myc inhibition protein). RNA was extracted after 24 hours.

first: Edoardo

last: Sarti

first: Cédric

last: Dollé

first: Rebekka

last: Wolfensberger

first: Katharina

last: Kusejko

first: Doris

last: Russenberger

first: Simon

last: Bredl

first: Roberto

last: Speck

first: Melanie

last: Greter

first: Jan

middle: H

last: Rueschoff

first: Lucas

last: Boeck

first: Dat

last: Mai

first: Ana

last: Jahn

first: Elizabeth

last: Gold

first: Dong

last: Liu

first: Alan

last: Diercks

first: Peter

last: Sander

first: Gregory

last: Olson


title: Mesenchymal stromal cells from JAK2V617F myeloproliferative neoplasms support healthy and malignant haematopoiesis in a humanised scaffold model in vivo

city: LONDON

first: Giuseppe

middle: Alessandro

last: D'Agostino

state: ENGLAND

address: 1 Midland Road

institute: The Francis Crick Institute

summary: Myeloproliferative Neoplasms (MPN) are malignancies of hematopoietic stem and progenitor cells (HSPCs) that lead to the overproduction of mature blood cells. These disorders include Essential Thrombocythemia (ET), Polycythaemia Vera (PV), and Primary Myelofibrosis (PMF), primarily driven by somatic mutations such as JAK2V617F. Research indicates that mesenchymal stromal cells (MSCs) support fibrosis in PMF, though their role in ET and PV remains less clear. Furthermore, in vivo studies of ET/PV HSPCs remain a challenge due to low engraftment levels in xenograft models.

overall_design: We employed a 3D scaffold model to create an MPN humanised xenograft mouse model, enabling in vivo functional studies of primary MPN progenitor cells and the supportive role of human MSCs. Using this model, we first demonstrated robust haematopoietic support of healthy (HD) HSPCs by PV and ET MSCs. We then investigated the role of MSCs in sustaining JAK2V617F mutant cells by using a CRISPR-Cas9 editing model, along with primary PV and ET HSPCs. Our results showed consistent engraftment of CRISPR-edited JAK2V617F mutant HSPCs and PV and ET patient-derived HSPCs in scaffolds seeded with HD, PV, and ET stroma, providing the first in vivo evidence that PV and ET MSCs can sustain both healthy and MPN-associated haematopoiesis. Furthermore, HD MSCs were also capable of sustaining PV and ET HSPCs in vivo. Overall, we present the first humanised MPN xenograft model that offers valuable insights into how human BM MSCs interact with JAK2V617F mutant clones.

first: Alessandra

last: Ferrelli

first: Dominique

last: Bonnet


title: Transcriptomics analysis of the hippocampus in Kdm1a/Kdm5c double-inducible forebrain-specific knockouts

city: San Juan de Alicante

first: Sergio

last: Niñerola

state: Alicante

address: Avenida Santiago Ramon y Cajal, s/n

department: Molecular Neurobiology and Neuropathology

institute: CSIC-Instituto de Neurociencias de Alicante

summary: Loss or reduced expression of lysine demethylases (KDMs) is linked to neurodevelopmental disorders and intellectual disability. Given the phenotypic similarities between KDM1A and KDM5C deficient mice, and the convergence of both enzymes in maintaining a repressive state via H3K4 demethylation, we examined their functional interaction using double-inducible, forebrain-specific knockouts (dKDM-ifKOs). These mice showed transcriptional and epigenetic dysregulation beyond the additive effects of individual knockouts, including stronger ectopic expression of non-neuronal genes in hippocampal neurons. Thousands of de novo H3K4me3-enriched regions emerged, indicating synergistic disruption of chromatin regulation. In line with these molecular changes, dKDM-ifKOs displayed more severe behavioral impairments than the single ifKOs, along with altered hippocampal expression of ion channels and increased excitability of CA1 pyramidal neurons. These findings underscore the joint role of ID-linked KDMs in regulating cell-type-specific gene silencing and H3K4 methylation levels to safeguard neuronal identity and responsiveness, as well as cognitive function

overall_design: Kdm1af/f, Kdm5cf/f and CamKIIα-CreERT2 mouse strains have been previously described , they are available at public repositories (Jackson Lab stock #23969; MMRRC stock 066789-UCD; and EMMA EM:02125, respectively). Mice were maintained on a C57BL/6J genetic background. The recombinant protein CreERT2 is dependent on tamoxifen (TMX) administration, and its expression is restricted to principal neurons of the forebrain, where CamKIIα is expressed. CaMKIIα–driven, TMX induced Cre recombination results in the elimination of exons 5 and 6 in Kdm1af/f and exons 11 and 12 in Kdm5cf/f . Mice were 2 to 3-month-old at the time of TMX administration.

first: Niñerola

last: Sergio

first: Paraiso-Luna

last: Juan

first: Barco

last: Angel


title: KDM5C binding profile in hippocampal chromatin

overall_design: Kdm5cf/f, and CamKIIα-CreERT2 mouse strains are available at public repositories (MMRRC stock 066789-UCD; and EMMA EM:02125, respectively). Mice were maintained on a C57BL/6J genetic background. The recombinant protein CreERT2 is dependent on tamoxifen (TMX) administration, and its expression is restricted to principal neurons of the forebrain, where CamKIIα is expressed. CaMKIIα–driven, TMX induced Cre recombination results in the elimination of exons 11 and 12 in Kdm5cf/f . Mice were 2 to 3-month-old at the time of TMX administration.


title: scHiCAR: a tri-modal single-cell genomics technology for integrated transcriptome, epigenome, and 3D genome analysis in complex tissues [mouse_brain_scHiCAR_2]

city: Durham

first: Yarui

last: Diao

address: 307 Research Drive

department: Cell Biology

institute: Duke University

summary: The three-dimensional (3D) organization of cis-regulatory elements (CREs) plays a central role in transcription control. However, capturing transcriptome, epigenome, and 3D genome from the same single cells remains technically challenging. Here, we present scHiCAR (single-cell Hi-C with ATAC and RNA-seq), a combinatorial barcoding-based method that simultaneously profiles mRNA, open chromatin, and chromosome-conformation-capture from the same cells. Compared to existing single-cell 3D genome methods, scHiCAR more efficiently enriches long-range cis-interactions anchored at candidate CREs (cCREs). Applied to 1.62 million mouse brain cells and complemented with a deep learning-based loop caller, scHiCAR accurately defines cell-type-specific transcriptomes, accessible cCREs, and 5kb-resolution enhancer-promoter pairs across 22 brain cell types. scHiCAR also performs robustly in challenging tissues such as skeletal muscle, enabling tri-modal single-cell level analysis of gene regulation dynamics during muscle stem cell regeneration. scHiCAR offers a scalable, efficient, and cost-effective platform for studying gene regulatory landscapes in complex tissues at single-cell resolution.

overall_design: To demonstrate the utility of scHiCAR for high-throughput analysis, we profiled 1.62 million mouse brain nuclei with matched RNA and DNA barcodes from four batches experiments, with three pilot experiments and one large scale experiment recovering 1.2M nuclei.

first: Xiaolin

last: Wei

first: Yueyuan

last: Xu

first: Dongchan

last: Yang


title: Regulation of Feather Length: FGF/IGF Signaling and NOTCH/YAP Modulation of Progenitor Cell Topology [bulk RNA-seq]

city: Los Angeles

first: Ping

last: Wu

state: California

address: 2011 Zonal Ave HMR313A

institute: University of Southern California

summary: The regulation of organ size is a fundamental biological question. This study investigates how feather length is regulated in chickens. We found collar bulge stem cell zones vary in size: main sickle > lesser sickle > contour feathers. During growth, IGF and FGF9 signaling are highly expressed, while BMP, WIF1 and FGF18 increase toward growth termination. Functional assays show that IGF/FGF signaling promotes feather elongation via tyrosine kinase receptor signaling. scRNA-seq analysis reveals accelerated differentiation of keratinocytes in short contour feathers compared to long sickle feathers. In Phoenix chickens, superlong main sickle feathers exhibit specialized stem cell zones with enhanced DLL1 expression and expanded intermediate-layer cell clusters with dynamic interactions involving NOTCH1/DLL1, YAP1, and WNT signaling in progenitor zones in the proximal follicle. Perturbation experiments induce short feather phenotypes arrested at various stages, shedding light on versatile regulatory mechanisms and paving the way for functional control of diverse feather lengths.

overall_design: Bulk RNA-seq for 3 stages of feather progenitor zone , single cell RNA-seq for feather follicles from White leghorn chicken and Phoenix chicken

first: Federico

last: Bocci

first: Qing

last: Nie

first: Cheng-Ming

last: Chuong


title: Integrated Systems Biology Identifies Disruptions in Mitochondrial Function and Metabolism as Key Contributors to HFpEF

status: Public on Aug 21 2025

city: Louisville

first: Andrew

middle: A.

last: Gibb

state: KY

address: 580 S Preston, Baxter II, 404C

institute: University of Louisville

summary: HFpEF accounts for ∼50% of HF cases. The ZSF1-obese rat model recapitulates clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and diastolic dysfunction. Here, we used a systems biology approach to define the metabolic and transcriptional signatures to gain mechanistic insight into pathways contributing to HFpEF development. The integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential interventional target.

overall_design: RNAseq was performed from 6 male WKY (control/wildtype group), ZSF1-Lean (Hypertensive group), and ZSF1-Obese (Hypertensive and metabolic syndrome; HFpEF group) rats.

first: John

last: Elrod

first: David

last: Lefer

first: Yinfei

last: Tan


title: Modeling aspects of human early post-implantation development with stem cells

status: Public on Aug 20 2025

city: Dallas

first: Leijie

last: Li

state: Texas

address: 5323 Harry Hines Blvd.

department: Molecular Biology

institute: UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER

summary: Early post-implantation development in humans, often a 'black box' due to limited access to natural embryos, has recently been studied using integrated stem cell-based embryo models (SCBEMs) that include most, if not all, embryonic and extraembryonic cell types. However, these models face challenges in reproducibility, efficiency, genomic and epigenomic stability, and/or fidelity, necessitating further development and refinement. Here, we have optimized a method for generating SCBEMs by combining primed human pluripotent stem cells (hPSCs) with transgene-induced extraembryonic cells from naïve hPSCs. The resulting inducible SCBEMs (iSCBEMs) effectively mimic key features of early post-implantation human concepti, including the development of amniontic, yolk sac and chorionic cavities, differentiation of syncytiotrophoblast-like cells forming lacunae, bilaminar disk formation, the establishment of the A-P axis and early stages of gastrulation. Human iSCBEMs offer a valuable alternative for studying early human post-implantation development.

overall_design: To investigate whether the generated iSCBEMs successfully mimic human post-implantation embryo development at the single-cell transcriptomic level, we subjected samples from Day 0 (starting cells), Day 3, Day 5, and Day 7 of the iSCBEM protocol to the 10x Genomics Chromium platform.

first: Seiya

last: Oura

first: Jun


title: Antisense transposon insertions into host genes trigger piRNA mediated immunity

city: Vienna

first: Dominik

last: Handler

address: Dr. Bohr-Gasse 3

country: Austria

institute: IMBA-Institute of Molecular Biotechnology of Austrian Academy of Sciences

summary: Transposable elements pose a persistent threat to genome integrity, yet how host defense systems adapt to newly invading elements remains poorly understood. Here, we reveal how Drosophila melanogaster acquired PIWI-interacting RNA (piRNA)-mediated immunity against the recently invading endogenous retrovirus tirant. By integrating genetics, small RNA profiling, and population genomics, we identify two distinct modes of de novo piRNA biogenesis. The primary mechanism involves antisense insertions into the flamenco cluster, a well-established master locus for transposon control. Strikingly, we also find that antisense tirant insertions into 3′ UTRs of host genes robustly trigger piRNA production, a process driven by host gene transcription but independent of gene identity. These findings challenge prevailing models that link piRNA precursor specification to genomic origin or nuclear processing context. Instead, they uncover a flexible, general mechanism in which transposition into host gene exons represents a critical vulnerability for transposons: by generating chimeric antisense transcripts that are exported to the cytoplasm, transposons inadvertently initiate their own silencing, enabling rapid and adaptive genome defense against new invaders.

overall_design: small RNA-seq profiling from the Drosophila Synthetic Population Resources (DSPR) founder strains

first: Rafanel

last: Baptiste

first: Protsenko

last: Liudmila

first: Handler

last: Dominik

first: Brennecke

last: Julius

first: Senti

last: Kirsten-André


title: The Role of Bone Marrow Erythroblastic Niche in Supporting metastatic Growth [scRNA-Seq]

city: Plainsboro

first: Yong

last: Wei

state: NJ

address: LTL227 Wathington Road

institute: Princeton University

summary: Bone metastasis significantly compromises quality of life in advanced-stage breast cancer patients through severe pain, fractures, and decreased mobility. The role of bone-resident cells such as osteoblasts and osteoclasts in metastatic interactions is well-established, however, the contribution of hematopoietic stem cell (HSC) lineage cells in the bone marrow, which differentiate into both red and white blood cells, remains poorly understood. Employing an in vivo metastatic niche labeling system and single-cell RNA sequencing, we systematically identified and functionally validated novel stromal components critical for bone metastasis. This niche labeling system enabled metastatic cancer cells to directly label surrounding niche cells in vivo via mCherry secretion. Bone marrow cells proximal to the tumor, which absorbed the secreted mCherry, were characterized using single-cell RNA sequencing. Our analysis revealed a distinct macrophage population enriched in the metastatic niche. Further in-depth characterization of these niche-specific macrophages was performed through cell sorting and bulk RNA sequencing. This population was found to be specialized macrophages with iron metabolism capabilities, residing within the erythroid island to support erythropoiesis. We demonstrated that in the bone metastasis environment breast cancer cells hijacked the iron-rich macrophages to supply themselves with iron. To better survive in the hypoxic bone marrow microenvironment, tumor cells mimic erythroblasts by upregulating globin gene expression and heme synthesis genes. These findings underscore the critical role of iron-rich macrophages in supporting tumor growth in the bone and their significant impact on erythropoiesis, presenting novel therapeutic targets for managing bone metastasis and cancer-related anemia.

overall_design: The niche labeling system enabled metastatic cancer cells to directly label surrounding niche cells in vivo via mCherry secretion. E0771 breast cancer cell, engineered to express both GFP and secreted mCherry, was injected into mice via the caudal artery of 8-week-old female C57BL/6 Tyr-/- mice to develop bone metastasis. Only bone marrow cells proximal to the tumor uptook the secreted mCherry. The GFP-mCherry+ niche cells and GFP-mCherry- distal bone marrow cells were isolated from metasttic bone. Normal bone marrow cells were isolated from healthy control mice. Single cell RNAseq profiles were generated from these samples to characterize the niche composition.   In addition, E0771 tumor cells from primary site mammary fat pad and bone metastasis were sampled and single cell RNAseq profile were generated to characterize tumor cell composition.

first: Yujiao

last: Han

first: Jennifer

last: Miller

first: Wei

last: Wang

first: Yibin

last: Kang


title: Massively parallel analysis of genotype-dependent enhancer activity among atopic dermatitis genetic risk variants

status: Public on Aug 19 2025

city: Cincinnati

first: Matthew

last: Weirauch

address: 3333 Burnet Avenue

department: Center for Autoimmune Genomics and Etiology (CAGE)

institute: Cincinnati Children's Hospital Medical Center

summary:
Background
Atopic dermatitis (AD) is an inflammatory, pruritic disease of the skin with a complex etiology involving environmental and genetic factors. Numerous genetic risk loci for AD have been nominated through genome-wide association studies, with most associated variants residing in non-coding regions. However, further work is needed to understand how genetic variation contributes to disease-related alterations to gene expression.
Objective
Here, we use massively parallel reporter assays (MPRAs) to identify genetic risk variants with genotype-dependent regulatory activity within a set of 2,381 variants distributed among 49 independent atopic dermatitis risk loci.
Methods
We employed our MPRA library in HaCaT skin keratinocytes, TE-7 esophageal epithelial cells, and Jurkat T cells, enabling the identification of shared and cell-type specific variants with genotype-dependent enhancer activity. Stimulation of HaCaT and TE-7 cells with the cytokine IL-13 revealed 14 variants with stimulation-dependent allelic expression patterns, elucidating a likely role for genotypic variation in Th2-mediated inflammatory signaling in AD.
Results
In total, our approach discovered 96 allelic enhancer variants among all investigated cellular contexts, representing 32 independent AD risk loci. We discover a possible mechanistic role for AP-1 family transcription factors, as revealed by motif enrichment, genotype-dependent binding, and enhanced ChIP-seq signal at AD risk variants with allelic enhancer activity compared to variants with non-allelic enhancer activity.  We assign allelic enhancer variants to probable target genes, including previously identified risk genes such as KIF3A and FLG.
Conclusion
Collectively, our systematic, genome-scale approach implicates causal genotype-dependent gene regulatory mechanisms for the majority of AD risk loci, providing a unique resource for the discovery of the genetic mechanisms underlying this chronic inflammatory disease.

overall_design: We performed ChIP-seq of the transcription factors FOSL2 and JUNB in human HaCaT skin keratinocytes. Experiments were performed in three replicates for each factor.

first: Leah

last: Kottyan


title: The Role of Bone Marrow Erythroblastic Niche in Supporting metastatic Growth [BulkRNAseq]

overall_design: Bone metastastic model was generated by injecting breast cancer cell E0771 into the caudal artery of 8-week-old female Albino B6 mice. General macrophages (CD11b+F4/80+) and niche-specific macrophages (VCAM1+CD163+CCR3+) were isolated from the bone marrow of mice carrying bone mteastasis or healthy control mice through FACS sorting.Three biological replicates of each sample type were collected from different mice.


title: Spatial transcriptomics analysis of mouse liver tissue during Alcohol-associated liver disease development and resolution

city: Kansas City

first: Irina

last: Tikhanovich

state: Kansas

address: 3901 Rainbow blvd

institute: University of Kansas Medical Center

summary: We identified functionally distinct spatial niche conposition during ALD development and resolution.

overall_design: Mice were fed high fat Western diet and 20% alcohol in the drinking water (ALD model), mice were then placed on chow diet with plain water to assess disease resolution. 2 mice with high and low fibrosis were selected for each condition and analyzed on the same slide

first: Michael

last: Schonfeld


title: Genome-wide occupancy profiling of Hnf4a in iHepC [ChIL-seq]

city: Fukuoka

first: Atsushi

last: Suzuki

state: Fukuoka

address: 3-1-1 Maidashi, Higashi-ku

department: Medical Institute of Bioregulation

institute: Kyushu University

summary: We investigated which genomic regions the transcription factor Hnf4a, ectopically introduced to induce hepatocyte-like cells (iHepCs) from MEFs through direct reprogramming, binds to in iHepCs.

overall_design: We performed ChIL-seq analysis for Hnf4a in iHepC. The experiment was conducted as two biological replicates.

first: Ryoga

first: Kenichi

last: Horisawa