title: A Trisomy 21-Associated Hotspot CSF2RB Mutation in Human Microglia Confers Resilience to Alzheimer’s Disease [WGS]

city: Piscataway

first: Ziyuan

last: Ma

address: 604 Allison Rd

department: Cell Biology and Neuroscience

institute: Rutgers University

summary: While challenging, identifying individuals displaying resilience to Alzheimer’s disease (AD) and understanding the underlying mechanism holds great promise for the development of new therapeutic interventions to effectively treat AD. Recent studies indicate that somatic mutations in hematopoietic cells may lead to both the instigation and resilience to neurodegeneration. Down syndrome (DS), or trisomy 21, is the most significant genetic risk factor for AD. Interestingly, some DS individuals show resilience to AD neuropathology and do not exhibit dementia signs. Notably, DS individuals face a heightened risk of myeloid leukemia due to somatic mutations in hematopoietic cells. Microglia dysfunction is a central mechanism in AD etiology. Here we hypothesize that somatic mutations associated with DS myeloid leukemia may impart resilience to microglia against AD. Using CRISPR-Cas9 gene editing, we introduce a DS-linked hotspot CSF2RB A455D mutation into human pluripotent stem cell (hPSC) lines derived from both DS and healthy individuals. Employing hPSC-based in vitro microglia culture and in vivo human microglia chimeric mouse brain models, we show that in response to pathological tau, the CSF2RB A455D mutation suppresses type-1 interferon signaling in both DS and control human microglia, independent of trisomy 21 genetic background. This mutation also reduces neuroinflammation and enhances phagocytic and autophagy functions, ameliorating senescent and dystrophic changes in human microglia. Furthermore, the CSF2RB A455D mutation promotes the development of a microglia subcluster with tissue repair properties. Importantly, human microglia carrying CSF2RB A455D provide protection to neuronal function, such as neurogenesis and synaptic plasticity. When co-transplanted into the same mouse brains, human microglia with CSF2RB A455D mutation phagocytize, outcompete, and gradually replace human microglia carrying the wildtype CSF2RB gene following pathological tau treatment. Our findings suggest the potential use of hPSC-derived CSF2RB A455D microglia to develop effective microglial replacement therapy for AD and other age-related neurodegenerative diseases, even without the need of depleting endogenous senescent microglia prior to cell transplantation.

overall_design: To accurately assign cell identities in the CAGG-WT and Cont-A455D microglia co-transplanted scRNA-seq samples, we conducted whole genome sequencing (WGS) on their respective pluripotent stem cell lines. Single nucleotide polymorphisms (SNPs) were identified from the aligned WGS data and used to assign identities to individual cells.

first: Jin

last: Mengmeng

first: Ma

last: Ziyuan

first: Jiang

last: Peng


title: The gene expression of primitive macrophages derived from Down syndrome model mouse embryonic stem cells on differentiation day 12

status: Public on Nov 24 2025

city: Kyoto

first: Keiichi

last: Ishihara

state: Kyoto

address: 5 Misasagi Nakauchi-cho, Yanashina-ku

country: Japan

institute: Kyoto Pharmaceutical University

type: Expression profiling by high throughput sequencing

summary: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16, of which a large portion is homologous to human chromosome 21. We have shown that the number of microglia was decreased in the brain of Ts1Cje fetus, thereby we analyzed the effects of Ts1Cje trisomic region on differentiation of embryonic stem cells (ESCs) with genotype of Ts1Cje mice into primitive macrophages.

overall_design:
To elucidate the reason why the number of microgila is decreased in Ts1Cje embryos, we induced primitive macrophages from ESCs established from the Ts1Cje mice.
We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 differnt cells of 2 genotypes (wild-type and Ts1Cje).
Comparative gene expression profiling analysis of RNA-seq data for primitive macrophages derived from wild-type and Ts1Cje mouse ESCs.

first: Koki

last: Harada


title: Accelerated osteocytic citrate production in chronic kidney disease is associated with protection of the kidney

city: Ann Arbor

first: Jie Ren Gerald

last: Har

state: MI

address: 1011 N University Ave

country: USA

institute: University of Michigan School of Dentistry

summary: Patients with chronic kidney disease (CKD) face elevated fracture incidences, but mechanisms underlying CKD-related bone loss remain unclear. Using the adenine-induced chronic kidney injury (AdKI) murine model, we identified that AdKI induces dysregulated glucose metabolism in bones and kidneys via in vivo and ex vivo metabolic tracing. Ex vivo 13C-metabolic tracing of osteocyte-enriched femora revealed accelerated citrate production from [1,2-13C]-glucose and [U-13C]-glutamine in AdKI mice. These metabolic changes were observed together with increased circulating citrate and Slc13a5 overexpression in bones from AdKI mice. Thus, to explore the role of citrate in AdKI, we utilized mice harboring a loss of function mutation in the citrate importer SLC13A5 (Slc13a5R337*/R337*). Mutant mice displayed elevated osteocytic citrate production, elevated circulating citrate, without significantly worsened AdKI-related bone loss. Coincident with this, Slc13a5R337*/R337* mutant mice were significantly protected from loss of kidney function with attenuated AdKI-induced nephrolithiasis. We also confirmed that Slc13a5 is highly expressed in cortical bone compared to the kidney, suggesting the effect of the mutation is mediated by SLC13A5’s function outside the kidney. Altogether, this study finds that accelerated osteocytic citrate production in CKD is associated with protection of kidney function, and modulation of citrate handling may be a site for therapeutic intervention in CKD.

overall_design: RNASeq of tibia cortices, obtained from 12-week-old mice, after induction on 4 weeks of CKD diet (0.2% wt/wt adenine) or control diet (without adenine)

first: Lauren

middle: E

last: Surface


title: HIF1α gates tendon response to overload and drives tendinopathy independently from vascular recruitment

city: Zurich

first: Jess

middle: Gerrit

last: Snedeker

address: Lengghalde 5

department: D-HEST

country: Switzerland

institute: ETH Zurich

summary: To investigate the role for HIF1α stabilization in tendon pathology, we generated mice with a tendon cell-targeted knockout of von Hippel-Lindau (VHL) protein by intercrossing ScxCre mice, in which Cre recombinase is under the Scleraxis promoter, with mice carrying the loxP -flanked Vhl alleles. VHL acts as a ubiquitin ligase that marks HIFs for proteolytic degradation under normoxic conditions, thereby silencing the HIF dependent transcriptional program. Hence, Vhl knockout results in stabilization of HIFs. We then performed gene expression analysis of tail tendon fascicles to confirm the activation of a HIF-dependent angiogenic and metabolic transcriptional program in the knockout mice compared to the wild types.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for wild type and ScxCre;Vhlf/f tail tendon fascicles (TTFs)

first: Greta

last: Moschini

first: Archana

middle: G

last: Mohanan

first: Izabella

middle: S

last: Niewczas

first: Diane

last: Taylor

first: Patrick

middle: K

last: Jaeger

first: Amro

middle: A

last: Hussien

first: Stefania

middle: L

last: Wunderli

first: Olivia

last: Baumberger

first: Maja

last: Wolleb

first: Barbara

last: Niederoest

last: Bollhalder

first: Raphaela

last: Ardicoglu

first: Guillermo

last: Turiel

first: Evi

last: Masschelein

first: Sarah

last: Morice

first: Santiago

last: Ardiles

first: Lieke

last: Mous

first: Matthew

middle: R

last: Aronoff

first: Monika

last: Hilbe

first: Farah

last: Selman

first: Karl

last: Wieser

first: Sandro

middle: F

last: Fucentese

first: Fabian

last: Passini

first: Ulrich

last: Blache

first: Didier

last: Surdez

first: Helma

last: Wennemers

first: Dirk

last: Elewaut

first: Jonathan

last: Clark

first: Katrien

last: De Bock


title: Prostaglandin E2-EP2/EP4 signaling induces the tumor-infiltrating Treg phenotype for tumor growth

first: Ryuma

last: Matsuura

address: 53 Kawara-cho, Shogoin, Sakyo-ku, Kyoto City,

institute: Kyoto University

summary:
Foxp3+ regulatory T cells (Tregs) heavily infiltrate malignant tumors and restrict anti-tumor immunity. These tumor-infiltrating Tregs (TI-Tregs) adopt a distinct phenotype by expressing a unique set of genes including those encoding various co-stimulatory and co-inhibitory molecules. This TI-Treg gene expression signature is conserved in TI-Tregs across species and the types and stages of tumors, suggesting the presence of a common inducing mechanism or mechanisms in tumor microenvironment (TME). However, identity of such a mechanism remains elusive. Here, we show that prostaglandin E2 (PGE2) produced in TME directly acts on its receptor EP2/EP4 on Tregs to induce the TI-Treg phenotype. Indeed, PGE2 added to TCR-activated Tregs induces a set of genes, many of which are included in the reported TI-Treg signature genes, in both induced Tregs (iTregs) and naturally occurring Tregs (nTregs), in a manner dependent on EP2 and EP4 via cAMP-PKA pathway. This is not limited to phenotypic changes, as EP4 agonist-treated Tregs exhibit potent suppressive activity to CD8+ T cells and strongly inhibit their proliferation and survival.
Consistently, selective loss of EP2 and EP4 in mouse Tregs and pharmacological inhibition of EP2 and EP4 reduce expression of those genes in Tregs infiltrating LLC1 mouse syngeneic tumor, and significantly delay the tumor progression. In human FOXP3+iTregs, the expression of Treg signature genes, FOXP3, CD25 and CTLA4 as well as a typical TI-Treg signature gene, 4-1BB are significantly upregulated by PGE2-EP4 signaling. Furthermore, analysis of scRNA-seq of nasopharyngeal cancer patients demonstrates preferential expression of the TI-Treg signature genes in Tregs infiltrating the PTGShi tumor group compared to the PTGS2lo tumor group. These findings suggest that PGE2-EP2/EP4 signaling is one of the molecular mechanisms inducing the TI-Treg phenotype in TME.

overall_design: mRNA profiles of Foxp3+ iTreg and nTreg treated in vitro with PGE2 and an EP4 agonist, respectively, and tumor-infiltrating Treg sorted ex vivo from LLC1 tumor-bearing control mice and Treg-specific EP2/EP4 KO mice.

first: Shuh

last: Narumiya


title: The Ionotropic AMPA receptor contributes to autoimmunity via altered regulatory T cell differentiation and function

city: Baltimore

first: Drew

last: Pardoll

state: Maryland

address: 1650 Orlean St.

department: Oncology

institute: Johns Hopkins Medical Institute

summary: To investigate the differential gene expression profile of G123KO iTreg vs. WT iTreg.

overall_design: We performed the gene expression profile on day 3 differentiated WT and G123KO iTreg cells.

first: Marisa

last: Mitchell-Flack

first: Hong

last: Yu


title: Disc-Derived Induced Pluripotent Stem Cells and Environmental Cues for Nucleus Pulposus Regeneration

city: Utrecht

first: Frank

last: Riemers

address: Uppsalalaan 8

country: Netherlands

institute: Utrecht University

summary: Notochordal cells (NCs) are linked to a healthy state of the nucleus pulposus (NP) and are therefore considered a promising candidate for cell-based regenerative therapies. However, NCs are scarcely available as they are lost early in life, and attempts at in vitro expansion have failed because NCs lose their specific phenotype. The generation of notochordal-like cells (NLCs) from human induced pluripotent stem cells (hiPSCs) is considered a viable alternative. Therefore, this study aimed to build on the instructive capacity of decellularized notochordal cell-derived matrix (dNCM) and the epigenetic memory of tissue-specific hiPSCs derived from TIE2+ nucleus pulposus-progenitor cells (NPPCs) to improve hiPSC differentiation towards mature, healthy matrix-producing NLCs. As a comparison, donor-matched minimally invasive peripheral blood mononuclear cell (PBMC)-derived hiPSCs were generated. The results showed that the use of tissue-specific derived hiPSCs instructed by a mix of natural cues provided by dNCM allowed for an improved differentiation capacity, indicated by the increased expression of key phenotypic and functional NC/NPC markers. Additionally, within this in vitro environment, the cell-source influenced off-target differentiation resulting in increased neural- and immune-cell fate for the PBMC-derived hiPSC lines. In the end, Understanding how in vivo microenvironmental cues will direct differentiation and maturation of the hMEPCs is imperative to refine the differentiation protocol also taking into account the hiPSC-derived NLC functionality and survival within the challenging environment of the intervertebral disc.

overall_design: Donor-matched intervertebral disc biopsies and blood samples of three patients (no 190, 191, 192) were collected at Inselspital in Bern after informed consent and ethical approval (no. b2019-00097). Both cell types were reprogrammed using Sendai virus vectors carrying the Oct4, Klf4, Sox, Myc (OSKM) reprogramming factors. The iPSC lines were differentiated into mesendoderm progenitor cells (MEPCs) according to the publish protocol by Warin et al. (2024) (https://doi.org/10.1016/j.isci.2024.109018).  At this timepoint the cells were transfected with NOTO mRNA and simulteneously plated into low-adherent culture plates to obtain 3D cell pellets of 35,000 cells in NP-genic medium (hgDMEM  (11965, Thermo Fisher) supplemented with 1% ITS+, 40 µg/ml L-proline (P5607, Sigma-Aldrich), 1% NEAA, 50 µg/mL Ascorbic acid-2-Phosphate (ASAP; A8960, Sigma-Aldrich), and 10 ng/mL TGF-β1 (240-B-010, R&D Systems, Minneapolis, USA)). On day 7, half of the samples were switched to NP-genic medium in which the TGF-β1 was replaced by decellularized notochordal cell-derived matrix, the other half was continued in TGF-β1. The sample were cultured until day 28 with daily medium refreshment whereafter they were collected for histology, biochemical analysis, and gene expression profiling.

first: Lisanne

middle: T

last: Laagland

middle: M

first: Deepani

middle: W

last: Poramba Liyanage

first: Romain

last: Desprat

first: Paul

last: Bensadoun

first: Keita

last: Ito

first: Anne

last: Camus

first: Jean-Marc

last: Lemaitre

first: Marianna

last: Tryfonidou


title: Single cell RNA-sequencing reveals RNA sequencing gene expression profiles between normal skin and wound edge in Hdac5fl/fl and K14cre;Hdac5fl/fl micecellular heterogeneity and trajectories of lineage specification

city: Shanghai

first: Yifan

last: Zhang

address: No.639, Zhizaoju Road

department: Department of Plastic and Reconstructive Surgery

country: China

institute: Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine

summary: Re-epithelialization is a crucial process in skin wound healing.  To date, the underlying mechanisms of re-epithelialization remain elusive, and effective strategies have not yet been developed.  Histone deacetylase 5 (HDAC5), classified as a class IIa HDAC protein, primarily modulates chromatin accessibility and regulates transcriptional activity through deacetylating lysine residues on core histones.   Additionally, it engages in interactions with several transcription factors, notably the extensively researched myocyte enhancer factor 2 (MEF2), influencing the expression of MEF2-dependent genes.   Beyond histone proteins, HDAC5 has exhibited non-histone deacetylase activity, targeting substrates like tubulin and p65.   Given that the successful activation of silent genes is pivotal for an effective regeneration process, the regulatory role of HDAC5 in the transcription of genes associated with regeneration underscores its potential in wound repair.   Therefore, in this study, we investigated the differences in gene expression in the skins of hdac5 conditional knockout mice and their wild-type littermates under normal conditions and after wounding.

overall_design: To explore the influence of HDAC5 on gene expression profiles in both normal skin and wound edge, we developed a model utilizing epidermal Hdac5 gene conditional knock-out K14cre;Hdac5fl/fl mice.   Employing the excisional wound splinting model, we procured the wound edge specimens for analysis.

first: Ya

last: Gao

first: Qingfeng

last: Li

first: Dongsheng

last: Wen

first: Chia-kang

last: Ho


title: ATAC-seq between normal skin and wound edge epidermis in Hdac5fl/fl and K14cre;Hdac5fl/fl mice

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: To explore the influence of HDAC5 both normal skin and wound edge, we developed a model utilizing epidermal Hdac5 gene conditional knock-out K14cre;Hdac5fl/fl mice.  Employing the excisional wound splinting model, we procured the wound edge specimens for analysis.


title: Gene expression and chromatin accessibility in human embryonic stem cells with partial deletion of PDHB during DE differentiation [RNA-seq]

city: WuHan

first: liming

last: meng

address: No. 115, Donghu Road

institute: WuHan university

summary: We established a PDHB heterozygous cell line in human embryonic stem cell HUES8. Then we performed definitive endoderm (DE) differentiation using both WT and PDHB partial deletion cell lines, and assessed gene expression and chromatin accessibility changes during this process by RNA-seq and ATAC-seq. Differentially expressed genes and regions with altered chromatin accessibility showed that in the PDHB-deleted cell line, the efficiency of endoderm differentiation was significantly inhibited. This alteration primarily occurred through changes in chromatin accessibility at BAF complex binding sites on DNA, which is a major ATP-dependent chromatin remodeling complex. And we also detected the SMAD2/3 binging by ChIP-seq.

overall_design: We performed the DE differentiation in WT and PDHB partial deletion cells. The DE differentiation medium was based on DMEM and supplemented with 100 ng/mL Activin A, 1x penicillin/streptomycin, and 0.2% bovine serum albumin. After the differentiation, we performed the RNA-seq and ATAC-seq in both cells. Besides that, we performed the SMAD2/3 ChIP-seq in WT cells. Detection was carried out after 3 days of induction using the same system.

first: Liming

last: Meng

first: Jie

last: Yang

first: Wei

last: Jiang


title: Timing of transcription controls the selective translation of newly synthesized mRNAs during acute environmental stress

city: Zürich

first: Mostafa

last: Zedan

address: Otto-Stern-Weg 3

institute: ETH-Zurich

summary: Upon acute stress, cells switch from pro-growth to stress-responsive gene expression programs to promote adaptation, by mounting rapid transcriptonal and translational responses. How these parallel responses are coordinated to selectively switch gene expression is poorly understood. Here, we show that following acute glucose withdrawal, yeast cells do not first degrade its old, pro-growth mRNA that was produced before stress, or sequester them in microscopic P bodies, but rapidly represses their translation followed by accelerated decay. Transcriptional induction of an mRNA during stress is sufficient to escape translational repression. This suggests a model where cells can switch between gene expression programs by repressing the translation of old mRNA while providing preferred access for new mRNA to translation. This timing-controlled mechanism provides a general framework for rapid and selective regulation of gene expression in a sequence-independent fashion by elegant coordination of gene expression changes in the nucleus and cytoplasm.

overall_design: We performed RNA-seq analysis of total mRNA levels, as well as ribosome footprints, to analyze changes in mRNA abundance and translation following acute glucose withdrawal of yeast cells. We further quantified polysomes enrichment for an inducible reporter as well as endogenous transcripts following acute glucose withdrawal. In addition, we  performed SLAM-seq for pulse chase analysis of mRNA decay in the presence or absence of glucose, and for analysis of polysomes enrichment of newly-made mRNA under glucose withdrawal conditions.


title: Injury-Induced CLU-Positive Cardiomyocytes Drive Metabolic Reprogramming of Macrophage Function in Heart Regeneration

first: Qi

last: Tang

address: 320 Yue Yang Road

institute: CAS Center for Excellence in Molecular Cell Science

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

overall_design: Refer to individual Series


title: A Trisomy 21-Associated Hotspot CSF2RB Mutation in Human Microglia Confers Resilience to Alzheimer’s Disease

first: Ziyuan

last: Ma

state: NJ

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Injury-Induced CLU-Positive Cardiomyocytes Drive Metabolic Reprogramming of Macrophage Function in Heart Regeneration [10X_chromium]

summary: The regenerative capacity of the adult mammalian heart is constrained by the post-mitotic nature of cardiomyocytes (CMs). Conversely, neonatal mouse hearts exhibit a regenerative window within the first week of life. Here, we demonstrate that an injury-induced Clusterin-positive (Clu+) CM population reprograms macrophages, facilitating heart regeneration during this timeframe. Clu+ CMs are selectively induced in the border zone of regenerative hearts across multiple species, contrasting with their absence in non-regenerative hearts. Genetic ablation of Clu+ CMs or Clu impedes neonatal heart regeneration, while transplantation of engineered human organoids enriched in Clu+ CMs or Clu overexpression promotes myocardial regeneration in adult mice. Mechanistically, Clu+ CMs secrete CLU, binding to TLR4 in macrophages, directing them toward an immune-suppressive neonatal-like phenotype through Cpt1a-mediated metabolic reprogramming, inducing BMP2 and promoting CM proliferation. Our findings unveil a novel cellular source for mammalian heart regeneration and highlight the fundamental roles of cardio-immune interaction in cardiac repair.

overall_design: 1) For atla of regeneration heart: we performed Apex Resection (AR) on postnatal day 1 mice (P1)  and collected cells from the regenerating apex for single-cell RNA sequencing (scRNA-seq) at P1, 1, 3, and 7 dpr covering injury, border, and remote regions. 2) For Clu-overexpressed P8-heart: we overexpress Clu and GFP in mouse at P4,and performed Apex Resection at P8. After 3days, we sorted  CD45+ cells from both the control and AAV-Clu groups for scRNA-seq.

first: Lei

last: Fan

first: Yutong

last: Wang


title: A Trisomy 21-Associated Hotspot CSF2RB Mutation in Human Microglia Confers Resilience to Alzheimer’s Disease (scRNA-Seq)

overall_design: To examine the impact of the CSF2RB A455D mutation on DS microglia, we utilized CRISPR–Cas-9-mediated gene editing to generate DS hiPSC lines carrying the CSF2RB A455D (DS-A455D) mutation. Subsequently, we differentiated DS WT and DS A455D hiPSCs into primitive macrophage progenitor (PMP) cells, denoted as DS-WT and DS-A455D PMP. To investigate potential transcriptomic changes induced by the A455D mutation in DS PMP, we conducted RNA-seq analysis on DS-WT and DS-A455D PMP.

first: Mengmeng

last: Jin

first: Peng


title: Injury-Induced CLU-Positive Cardiomyocytes Drive Metabolic Reprogramming of Macrophage Function in Heart Regeneration [Spatial Transcriptomics]

overall_design: we performed Apex Resection (AR) on postnatal day 1 mice (P1)  and collected largest cross-section from the OTC-embbeded heart for spatial transcriptomics at P1, 1, 3, and 7 dpr


title: Injury-Induced CLU-Positive Cardiomyocytes Drive Metabolic Reprogramming of Macrophage Function in Heart Regeneration [stero-seq]

overall_design: we overexpress Clu and GFP in mouse at P4,and performed Apex Resection at P8. After 3days, we collected largest cross-section from the OTC-embbeded heart for spatial transcriptomics.


title: RNA-seq for localis-REX project

city: Lausanne

first: Dalu

last: CHANG

state: Not US or Canada

address: EPFL SB ISIC LEAGO, CH A2 397,Station 6

institute: EPFL,

summary: Localis-REX has been developed by our lab.In the current project, we aim to study transcriptomics changes under Localis-REX within different subcelluar locations. Localis-REX coupled RNA-seq would give us a borad idea of mRNA changing under our reaction conditon over mutiple controls

overall_design: Localis-REX was performed in human cell lines, with one reaction condtion, and three controls. And RNA was isolated at three time points, 3hrs, 6hrs, or 12 hrs after reaction or controls.

last: Chang

first: Yimon

last: Aye


title: Molecular and phenotypic blueprint of the hematopoietic compartment reveals proliferation stress as a driver of age-associated human stem cell dysfunctions

city: Toronto

first: Alexander

middle: James

last: Murison

state: Ontario

address: 101 College Street, TMDT room 11-706

country: Canada

institute: University Health Network

summary: Hematopoietic stem/progenitor cell (HSPC) aging studies have been associated with myeloid skewing, reduced clonal output, and impaired regenerative capacity, but quantitative immunophenotypic and functional analysis across human aging is lacking. Here, we provide a comprehensive phenotypic, transcriptional, and functional dissection of human hematopoiesis across the lifespan. Although primitive HSPC numbers were stable during aging, overall cellularity was reduced, especially for erythroid and lymphoid lineages. Notably, HSPC from aged individuals had superior repopulating frequency than younger counterparts in xenografts; yet aged HSPC displayed epigenetic dysregulation of cell cycle, inflammatory signatures, and a reduced capacity to counteract activation-induced proliferative stress with concomitant accumulation of DNA damage and senescence-like features upon xenotransplantation. This phenotype was recapitulated by enforcing proliferative stress in vivo on cord blood (CB) HSPC. Overall, our work sheds light on dysregulated responses to activation-induced proliferation underlying HSPC aging and establishes CB xenotransplantation-based models as suitable for studying age-associated hematopoietic defects.

overall_design:
Hematopoietic stem and progenitor subpopulations were isolated from  frozen human bone marrow cells by flow sorting and prepared for ATAC-seq. The set of samples that passed quality control  (n=31 subfractions, n=3 young donors (21-28y), n=4 mid/old donors (52-79y)) are included in this submission

Submitter states that missing raw data are being made available for controlled access in EGA.

first: Stephanie

middle: Z

last: Xie

first: Laura

last: Garcia-Prat


title: ARID1A recruits TRIM28 for the essential remodeling of heterochromatin independent of SWI/SNF [ChIP-seq]

first: Nestor

last: Zhang

address: Dongchuan Road

institute: Shanghai Jiao Tong University

summary: ARID1A functions as a vital tumor suppressor whose activity usually depends on the SWI/SNF chromatin remodeling complex. ARID1A is highly mutated across human cancers, and its deficiency has been found to promote immunogenicity through impaired mismatch repair and elevated tumor mutation burden. However, little is known about the SWI/SNF-independent function of ARID1A and the subsequent consequences. Here, we report a novel mechanism of action that ARID1A maintains heterochromatin integrity and silences endogenous satellite/retroelements, independent of SWI/SNF and microsatellite instability. Mechanistically, ARID1A recruits TRIM28 to keep the rigidity of heterochromatin. Loss of ARID1A displaces SETDB1 from TRIM28-contraining heterochromatin complex to induce the derepression of H3K9me3 at endogenous satellite/retroelement regions. The unleashed satellites and retroelements resulting from impaired ARID1A-TRIM28 interaction trigger type-I interferon immune responses, promoting tumor progression and sensitivity to PD1 blockade through both RNA- and DNA-sensing pathways. Our results shed light on the SWI/SNF-independent function of ARID1A to necessarily maintain heterochromatin integrity and safeguard the immunogenicity, potentiating the disruption of ARID1A-TRIM28 interaction as a strategy to convert ARID1A-wildtype tumors into hot to strengthen the therapeutic efficacies.

overall_design: we performed ChIP-seq for ARID1A, H3K9me3,TRIM28 and SETDB1 in control (shCtrl) and ARID1A-loss (shARID1A) HCT116 cells to evaluate the  the potential interrelation between ARID1A and heterochromatin.

first: Qian

last: Li

first: Zhe

first: Jianfeng

last: Shen


title: A Trisomy 21-Associated Hotspot CSF2RB Mutation in Human Microglia Confers Resilience to Alzheimer’s Disease (bulk RNA-Seq)


title: Tissue-specific restriction of transposon-derived regulatory elements safeguards cell-type identity

first: Evarist

last: Planet

state: Vaud

address: Route Cantonale

institute: EPFL


title: ARID1A recruits TRIM28 for the essential remodeling of heterochromatin independent of SWI/SNF [RNA-seq]

overall_design: we performed RNA-seq of control (CTR) and ARID1A-loss (shARID1A) HCT116 cells to evaluate the potential interrelation between ARID1A and immune functions. (n=2)


title: An integrated multi-omics and network analysis of neutrophil differentiation from early- to late-stage [OCEAN-C]

city: Beijing

first: Cheng

state: Beijing

address: No.5 Yiheyuan Road, Haidian District

department: School of Life Sciences

institute: Peking University

summary: The goal of this study is to study the gene regulation mechanism during ATRA-induced HL-60 cell neutrophil differentiation especially in the early time-point. We demonstrated the striking early changes event that trigger the whole differentiation process. We also identified the pioneer TFs (Transcription factors) that ignite the differentiation process with the corresponding TF correlation networks.

overall_design: Genome-wide mapping of transcriptomic, chromatin accessibility, and chromatin interaction in differenti time-points during neutrophil differentiation.

first: Wei

first: Minglei

last: Shi

first: Qing

last: Chen


title: Fetal brain RNA-seq of DSS treated or DSS+ Gsdmd-cko

status: Public on Nov 23 2025

city: beijing

first: huiyang

last: Jia

address: China

institute: Institute of Zoology, Chinese Academy of Sciences

summary: The maternal mice had two genotypes: wild-type (WT) and conditional knockout of intestinal epithelial Gsdmd (Gsdmd cko). Pregnant mice were treated with DSS starting on gestational day 9.5 (GD9.5) for 4 days, and immediately afterward, the cortex of fetuses at embryonic day 13.5 (E13.5) was dissected for RNA sequencing.

overall_design: Establish the model using DSS, and isolate the fetal cerebral cortex for sequencing four days later.


title: An integrated multi-omics and network analysis of neutrophil differentiation from early- to late-stage


title: Sequencing of colon epithelium from pregnant mice

summary: RNA sequencing was performed on the colorectal epithelium of pregnant mice in the normal group and the colitis group. For the colitis group, pregnant mice were treated with 2.5% DSS for 4 days starting on embryonic day 9.5 (E9.5); subsequently, CD326+ CD45- cells were sorted by flow cytometry for RNA sequencing.

overall_design: DSS Treated for 4 days.

first: Huiyang


title: Gene expression profile at single cell level of spinal cord infilitrating CD4 T cells at the peak of EAE disease

first: Drew

last: Pardoll

summary: We used single cell RNA sequencing to evaluate the molecular differences between WT and G123KO CD4 T cells in the context of EAE disesase.

overall_design: Immune cells were enriched from the spinal cord by a Percoll gradient protocol. Enriched cells were then further isolated to live CD4 T cells by fluorescence-activated cell sorting (FACS) and analyzed using scRNAseq.

first: Marisa

last: Mitchell-Flack

first: Hong

last: Yu


title: An integrated multi-omics and network analysis of neutrophil differentiation from early- to late-stage[RNA-Seq]


title: An integrated multi-omics and network analysis of neutrophil differentiation from early- to late-stage [ATAC-Seq]


title: Spatially controlled enhanced anti-tumor efficacy via CAR T cells engineered with a CTLA-4-based autoregulated circuit

city: Amsterdam

first: Afroditi

last: Katsarou

address: De Boelelaan 1117

department: Department of Hematology

institute: Amsterdam UMC location Vrije Universiteit Amsterdam

summary: The widespread application of CAR T cell therapy to solid tumors is hindered by antigen expression heterogeneity, on-target off-tumor toxicity, and limited functional persistence of CAR T cells. Next generation engineering strategies aiming to overcome these hurdles rely on multiple antigen-targeting approaches that  fail to simultaneously address all the limitations and/or the use of synthetic receptor transcriptional circuits, which suffer from slow activation kinetics. Here, we leveraged the unique trafficking properties of CTLA-4, regulated by a rapid internalization process, to create CTLA-4-based activation-inducible antigen receptors (CAVI-Rs). CAVI-Rs were exclusively expressed on T cells upon activation with remarkably fast on/off kinetics and self-sustainable expression. In in vitro and in vivo models of heterogeneous tumors, CAR+CAVI-R dual-engineered T cells demonstrated enhanced cytotoxicity and tumor-selective, spatially restricted functionality. Additionally, intermittent co-expression of the CAVI-R lead to improved T cell metabolic and transcriptional fitness, resulting in superior expansion, persistence and anti-tumor efficacy. The CAVI-R provides a novel, simple, safe, potent, and fully-human approach to expand CAR T cell applicability while improving anti-tumor outcomes.

overall_design: Double transduced CAR+CCR or CAR+CAVI-R T cells were cultured in 6-well tissue culture plates (Greiner Bio-One), with irradiated (60Gy) MM.1s cells in an E:T ratio of 2:1 and were expanded by weekly stimulations. T cell samples were isolated before the first stimulation (day 0) and at day 14 of expansion (day 14). T cells were stained and sorted (BD FACSMelody™ Cell Sorter) based on double positivity for dsRed (BCMACAR-dsRed) and LNGFR (CCR/CAVI-R-LNGFR) with 100% purity. Samples were spun down at 1500 RPM and stored at -80oC with RNALater (ThermoFischer) for further processing. RNA isolation was performed with RNeasy Plus Mini kit (Qiagen). Libraries were sequenced with the Illumina SBS technology at a sequencing depth of at least 75 million per sample (Macrogen). Paired-end reads were trimmed using Trimmomatic44 0.39 before mapping to the human transcriptome (Gencode v42)45 using Salmon 1.9.046. Mapping results were imported in R 4.4.0 using the Tximeta 1.22.1 package47 and features were annotated using biomaRt 2.60.0. Differential expression analysis was performed using DESeq2 1.44.048 and the results were ranked by -log10(p-value) * sign(foldchange). Geneset Enrichment Analysis was performed on the ranked results using clusterProfiler 4.12.049 and plotted using the dotplot function from Enrichplot 1.24.0. Volcanoplot was produced using EnhancedVolcano 1.22.0. Heatmap was produced by centering the counts to 0 after a variance stabilizing transformation using vst function from DESeq2 for genes of interest and plotting them using ComplexHeatmap 2.20.050, 51.

first: George

last: Kladis

first: Thomas

last: Baardemans

first: Maria

last: Themeli


title: The contribution of formyl peptide receptor 2 to intestinal epithelium homeostasis

first: shuting

address: 320 Yueyang Road, Xuhui District

institute: Shanghai Institute of Nutrition and Health

summary: To elucidate the mechanisms involved in maintaining intestinal epithelial homeostasis through formyl peptide receptor 1 (FPR2), small intestinal organoids derived from Fpr2f/f mice were used as an ex vivo model. Transcriptomics were examined via RNA-seq following FPR2 activation with MMK-1.

overall_design: RNA-seq profiling of small intestinal organoids derived from Fpr2f/f mice treated with 1 M MMK-1 or a vehicle control (0.1% DMSO) for 5 days.

first: Shuting

first: Yingying

last: Le


title: Gene Expression Analysis in Diet-Induced Obese Mice Treated with 10-epi PDX

city: Seoul

first: Nahyun

last: Kim

address: 120 Neungdong-ro, Gwangjin-gu, Seoul

country: South Korea

institute: Konkuk university

summary: Chronic inflammation and disrupted lipid metabolism are central drivers of obesity-associated metabolic dysfunction, yet the contribution of endogenous lipid mediators in counteracting these processes remains poorly defined. 10-epimer-protectin DX (10-epi PDX), a specialized pro-resolving mediator (SPM) derived from docosahexaenoic acid (DHA), has been suggested to regulate inflammation and lipid metabolism. Here, we investigated its in vivo role in obesity-driven metabolic dysfunction.

overall_design: Gene expression profiling analysis of RNA-seq data from diet-induced obese mice liver treated with 10-epi PDX


title: Small RNA genomics of Aedes aegypti mosquitoes discovers infectious viruses that trigger an RNA interference response [RNA-seq]

city: BOSTON

first: NELSON

middle: C

last: LAU

state: MA

address: 72 E Concord St K219, Dept of Biochemistry

department: Biochemistry and Cell Biology

institute: Boston University Chobanian & Avedisian School of Medicine

summary: We report a global survey of viral small RNAs (vsmRNAs) from >200 Aedes aegypti samples to identify many mosquito viruses that actively infect this prominent arboviral vector. Ae. aegypti viruses in the Americas were abundant, with some displaying geographical boundaries. Viruses infecting Asian Ae. aegypti were similar to those in the Americas and revealed the first wild example of dengue vsmRNAs. African Ae. aegypti displayed vsmRNAs from viruses unique to these African strains. Academic lab colonies generally lacked viruses, yet two commercial strains were deeply infected by a tombus-like virus that is related to plant viruses. Comparing matched viral long RNAs to vsmRNAs revealed viral transcripts evading the mosquito RNA interference (RNAi) pathway. By infecting mosquito cells with Ae. aegypti homogenates, we generated stably infected cell lines which produced vsmRNAs that were comparable to native mosquito vsmRNA patterns. Lastly, we demonstrate that these stably infected mosquito cells producing vsmRNAs can exert gene silencing of reporters bearing viral sequence segments, providing a potential explanation for how Ae. aegypti can tolerate the persistence of viral infections. This vsmRNA genomics approach in Ae. aegypti can add to existing vector surveillance approaches by discovering new viruses that persist in mosquito populations.

sample_organism:
Aedes aegypti
Aedes albopictus

platform_organism:
Aedes aegypti
Aedes albopictus

overall_design: Aedes aegypti mosquitoes from colonies and field collections from around the world where subjected to total RNA extraction.  This total RNA was then subjected to small RNA sequencing for all the collected samples, while a major fraction of the samples were also subjected to total RNA sequencing. Mosquito viruses from some of these samples were isolated and propogated on mosquito cell cultures to establish stably-infected cells, and the small RNAs and total RNAs from infected and mock control mosquito cells were also subjected to sequencing.  All the sequencing data was then analyzed for virus expression.

first: Shruti

last: Gupta

first: Rohit

last: Sharma

first: Adeline

last: Williams

first: Irma

last: Sanchez-Vargas

first: Noah

last: Rose

first: Chao

first: Alexander

last: Crosbie-Villaseca

first: Margarita

last: Kyza-Karavioti

first: Zheng

last: Zhu

first: Gargi

last: Dayama

first: Andrea

last: Gloria-Soria

first: Doug

last: Brackney

first: Jessica

last: Manning

first: Sarah

last: Wheeler

first: Angela

last: Caranci

first: Trinidad

last: Reyes

first: Massamba

last: Sylla

first: Athanase

last: Badolo

first: Jewelna

last: Akorli

first: Ogechukwu

last: Aribodor

first: Diego

last: Ayala

first: Wei-Liang

last: Liu

first: Chung-Hong

first: Chalmers

last: Vasquez

first: Cassandra

last: Acosta

first: Alongkot

last: Ponlawat

first: Tereza

last: Magalhaes

first: Brendan

last: Carter

first: Dawn

last: Wesson

first: Darred

last: Surin

first: Meg

last: Younger

first: Andre

last: Costa-da-Silva

first: Matthew

last: DeGennaro

last: Bergman

first: Louis

last: Lambrechts

first: Carolyn

last: McBride

first: Ken

last: Olson

first: Eric

last: Calvo

first: Nelson

last: Lau


title: Small RNA genomics of Aedes aegypti mosquitoes discovers infectious viruses that trigger an RNA interference response [miRNA-seq]

first: NELSON

last: LAU

type: Non-coding RNA profiling by high throughput sequencing

first: Shruti

last: Gupta

first: Rohit

last: Sharma

first: Adeline

last: Williams

first: Irma

last: Sanchez-Vargas

first: Noah

last: Rose

first: Chao

last: Zhang

first: Alexander

last: Crosbie-Villaseca

first: Margarita

last: Kyza-Karavioti

first: Zheng

last: Zhu

first: Gargi

last: Dayama

first: Andrea

last: Gloria-Soria

first: Doug

last: Brackney

first: Jessica

last: Manning

first: Sarah

last: Wheeler

first: Angela

last: Caranci

first: Trinidad

last: Reyes

first: Massamba

last: Sylla

first: Athanase

last: Badolo

first: Jewelna

last: Akorli

first: Ogechukwu

last: Aribodor

first: Diego

last: Ayala

first: Wei-Liang

last: Liu

last: Chen


title: Single-Cell RNA-seq analysis of small intestine neuroendocrine tumors reveals the cell of origin and trajectory of gene-expression associated with the early tumor development

city: BETHESDA

first: Cihan

last: Oguz

state: MD

address: NIHBC 29B BG RM 1NN20, 9000 ROCKVILLE PIKE

institute: NIH

summary: A hereditary form of small intestinal neuroendocrine tumors (SI-NET) presents with multiple synchronous primary tumors and accompanying tumor precursors at varying stages of development. Capitalizing on this germline property, we conducted single-cell RNA sequencing analysis to identify the cell-of-origin and explore the trajectory of gene expression associated with the early tumor development. The results of the current study may enhance our understanding of the genesis and development of SI-NETs and improve diagnostic, preventive, and therapeutic strategies.

overall_design: To characterize the overall landscape of epithelial and tumor cell gene expression, we analyzed scRNA-seq data from nine control mucosa (CM) samples, nine patient mucosa (PM) samples and 16 patient tumor mucosa (PTM) samples.

first: Yoshitatsu

last: Sei

first: Joanne

last: Forbes

first: Paul

last: Schaughency

first: Gustavo

last: Gutierrez-Cruz

first: Faiza

last: Naz

first: Stephen

last: Brooks

first: Stefania

last: Dell’Orso

first: Pradeep

last: Dagur

first: Jianying

last: Feng

first: Xilin

last: Zhao

first: Marybeth

last: Hughes

first: Naris

last: Nilubol

last: Wank


title: Intracellular traction forces modulate chromatin accessibility at the FOXO1 locus

city: Chengdu

first: Li

last: Liao

state: Sichuan

address: No. 24, South Section 1, First Ring Road

institute: SiChuan University

summary: In summary, our study demonstrates that cellular traction forces modulate cellular senescence by promoting chromatin accessibility, particularly at regions associated with FOXO1 expression. This localized chromatin remodeling facilitates FOXO1 activation, which serves as a critical mediator linking cell mechanics to transcriptional and functional changes that regulate senescence. These findings highlight the role of mechanical forces in orchestrating chromatin dynamics and underscore FOXO1 as a key target in the mechanotransduction-mediated regulation of aging.

overall_design: Bone marrow aspirates were obtained from patients aged 60–80 years (old group) and 18–30 years (young group). Bone marrow-derived mesenchymal stem cells (BMSCs) were cultured by plating 1 mL of bone marrow into T-75 flasks containing growth medium supplemented with 10% fetal bovine serum (Gibco). BMSCs at passages 1–2 was used for all downstream experiments. To enhance cellular traction forces, senescent BMSCs were seeded onto a stretching device (Cell&Force, Cell Tank, Hangzhou Surface&Force Technology Co., Ltd) and subjected to cyclic mechanical stimulation at 5% strain and 0.02 Hz for 2 h. Conversely, to attenuate traction forces, young BMSCs were cultured on soft hydrogels with a shear modulus of 1.5 kPa for 24 h.

first: Qiang

last: Wei

first: Xiaojing


title: A Single-Cell Transcriptomic Atlas Identifies Hierarchical Skeletal Progenitors and Zonal Patterning in Mouse Mandibular Cartilage

city: Okayama

first: Ikue

last: Tosa

state: Okayama

address: Shikata-cho2-5-1, Kita-ku

institute: Okayama University

summary: Skeletal and synovial joint development involves distinct skeletal stem/progenitor populations. However, in neural crest-derived temporomandibular joint (TMJ), skeletal stem/progenitor lineage dynamics and ossification programs remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on mouse mandibular cartilage at embryonic day 16.5 (E16.5), postnatal day 0 (P0), and 13 weeks to construct a high-resolution atlas of skeletal stem/progenitor populations. The outer perichondrium lining the mandibular cartilage contained Lgr5⁺Pthlh⁺ cells expressing Dlx5, suggesting intramembranous ossification. In contrast, a previously uncharacterized Crabp1⁺ subpopulation within the inner perichondrium expressed Nrg1, Lsamp, Tac1, and Igfbp5, consistent with early cartilage progenitors biased toward endochondral ossification. These results reveal a spatial division of ossification modes with both intramembranous and endochondral growth and clarify the transcriptional regulation underlying TMJ development. Our findings provide a framework for understanding neural crest–derived skeletal stem/progenitor cell regulation and may inform cartilage regenerative strategies.

overall_design: To characterize the cellular composition of the TMJ during development, we performed scRNA-seq on mandibular condylar cartilage from C57BL6 mice at three developmental stages: embryonic day (E) 16.5 (E16.5, formation of superior joint cavity), post-natal day (P) 0 (P0, initial use of TMJ), and 13-week-old (13w, adults).

first: Wakana

last: Kitagawa

first: Benjamin

last: Kheyfets

first: Ziyi

last: Wang

first: Hyerin

last: Yoon

first: Evan

last: Stipano

first: Mitsuaki

last: Ono

first: Mildred

last: Embree


title: Evaluation of 5-aminolevulinic acid-mediated radiodynamic therapy after single-dose irradiation in HT-29 xenografted mice

city: Kitakyushu

first: Junko

last: Takahashi

state: Fukuoka

address: 2-7 Hibikino, Wakamatsu-ku

department: Graduate School of Information, Production and Systems

institute: Waseda University

summary: We investigated changes in gene expression in HT-29 human colon carcinoma xenografts in nude mice after single-dose X-ray irradiation combined with 5-aminolevulinic acid (ALA)-mediated radiodynamic therapy. Control (non-irradiated, no ALA) and treated tumor samples were analyzed using Aglient Whole Human Genome Microarray 4x44K G4112F.

overall_design: Mice were implanted with HT-29 human colon carcinoma cells and divided into six groups: (1) no treatment (NT); (2) single administration of 5-aminolevulinic acid (5-ALA) without irradiation (ALAT); (3) 12 Gy single-dose X-ray irradiation alone (XT); (4) 100 mg/kg 5-ALA treatment followed by 12 Gy single-dose X-ray irradiation (A100-XT); (5) 200 mg/kg 5-ALA treatment followed by 12 Gy single-dose X-ray irradiation (A200-XT); (6) 10 daily administrations of 100 mg/kg 5-ALA followed by fractionated X-ray irradiation (2 Gy/day, total 20 Gy) (A100-20XT). treatment followed by fractionated irradiation (2Gy/day) (A100-20XT).


title: VEGFA Stop-gained Variant Deteriorates Cardiac Remodeling in Myocardial Infarction [scRNA-seq]

city: shanghai

first: Zhongxiang

last: Chen

state: Shanghai

address: 浦东新区东方路1678号上海儿童医学中心

institute: shanghai children's medical center

summary: A sustained dosage of Vascular Endothelial Growth Factor A (VEGFA) is crucial for angiogenesis in both homeostasis and cardiovascular diseases. CUG-initiated alternative translation is a conserved mechanism for producing mature VEGFA. Genetic surveys have identified stop-gained variants predicted to prematurely terminate CUG-initiated translation without affecting ATG-initiated translation. However, the impacts of these variants on the vasculature in steady-state and disease conditions remain unknown. Here, we identified that homozygous mice carrying the stop-gained variant were viable. VEGFA dosage reduced to 70% in the Q150X homeostatic heart, with no significant alteration in cardiac function or vasculature. In the MI model, VEGFA dosage in Q150X was reduced to about 40% within the first-week post-infarction, leading to functional deterioration in the post-MI hearts. Significant changes in cellular composition were observed three days post-MI. In particular, endothelial cells in Q150X diverged into a state that showed higher level of hypoxia stress, an elevated inflammatory response, and increased extracellular matrix secretion. Additionally, we observed an increase of Nppb+ stressed cardiomyocytes in both 3 days post-MI and homeostasis. Finally, pro-inflammatory macrophages, neutrophils, and Cd8+T cells were enriched in the ischemic zone of Q150X hearts. CUG-initiated translation contributes significantly to the production of mature VEGFA in ischemic hearts. VEGFA dosage is critical in determining the cellular microenvironment during ischemic injury.

overall_design: Using CRISPR/Cas9 genome editing, we established VegfaQ150X/Q150 allele (Q150X), a mouse genetic model that mimics the human VEGFA stop-gained variant. The effects of this variant were tested in both adult homeostatic conditions and the acute myocardial infarction (MI) model. We then performed gene expression profiling analysis using data obtained from bulk RNAseq of whole hearts, endothelial cells(EC) and cardiomyocytes(CM) and and single-nulceus RNAseq of whole hearts from WT and Q150X(HO)  at homeostasis(homeo) and different time points following MI.

first: Min

last: Zhang


title: p38 blockade reverses the immune suppressive microenvironment in metastatic breast cancer

city: Buffalo

first: Andrei

last: Bakin

address: Elm and Carlton streets

institute: Roswell Park Comprehensive Cancer Center

summary: The study investigated the role of p38α in regulating the outcome of the immune-tumor interaction in metastatic breast cancer. Single-cell transcriptomic analysis of the immune-TME showed that pharmacological p38 inhibition (p38i) or tumor-specific inactivation of p38α by CRISPR/Cas9 (p38KO) resulted in a less exhausted and more activated CD8+ T cell phenotype. Moreover, the myeloid cells in the TME exhibited reduced expression of immune-suppressive factors and chemotactic receptors. Overall, this study highlights a previously unrecognized p38α-driven pathway that promotes an immune suppressive TME and that therapeutic blockade of p38α has important implications for improving antitumor immunity and patient outcomes.

overall_design: 4T1 mouse mammary adenocarcinoma cells were modified to express luciferase reporter. Female BALB/c mice were implanted with 4T1-luc p38a wildtype cells (p38WT) or 4T1-luc cells with p38a genetically inactivated by CRISPR-Cas9 (p38a-KO-H9). Mice with palpable tumors in the p38WT cohort (day 4) were divided in two groups and treated with vehicle control (DPBS) or p38 inhibitor (LY2228820; 30mg/kg, daily gavage) for 10 days. At day 14 post implantation, tumors from 3 mice per group of comparable sizes were pooled together and single-cell suspensions were prepared by cold protease digestion methods. The cells were stained for CD45 (pan-immune cell marker) and 7AAD (live/dead). About 100,000 Live CD45+ cells (negative for 7AAD) were sorted using BDFACSAria II. The cells were resuspended in PBS + 0.04% FBS solution at a concentration of 1000 cells per sample. Immediately following preparation, cells were provided to the Roswell Park Genomics Shared Resource (GSR) for further processing and single cell sequencing (10x Genomics).

first: Priyanka

last: Rajan

middle: V

first: Scott

middle: I

last: Abrams


title: Piezo1-dependent gene expression in mouse colon cancer cell line CMT-93

city: Tsukuba

first: Yutaro

last: Kumagai

state: Ibaraki

address: Central 5-41, Higashi 1-1-1

department: BRD

institute: AIST

summary: A wild-type or Piezo1-deficient colon cancer cell line CMT-93 was stimulated with single-strand RNA (ssRNA) or Yoda-1, and gene expression was compared by using microarray.

overall_design: A wild-type or Piezo1-deficient colon cancer cell line CMT-93 was stimulated with single-strand RNA (ssRNA) or Yoda-1 for 24 hours and total RNA was subjected to microarray analysis.

first: Kenta

last: Maruyama


title: Integrin αV as a potential target in aortic aneurysm and dissection II

city: Hangzhou

first: Sheng-an

last: Su

state: Zhejiang

address: No. 88 Jiefang Road

institute: Zhejiang University

summary: Thoracic aortic aneurysm (TAA) is a perilous disease that can lead to aortic dissection (AD), the pathophysiological mechanisms of which remain largely elusive. To improve our understanding of the molecular mechanism underlying TAA, we conducted a tandem mass tag (TMT)-based proteomics analysis and identified two down-regulated proteins, integrin αV, and integrin αL, in serum samples from patients with type A aortic dissection. We confirmed that integrin αV is extensively expressed in the aortic media, and its expression decreases after dissection, whereas the expression of integrin αL showed no significant alteration. Subsequently, by employing a mouse model of TAA induced by β-Aminopropionitrile (BAPN), we discovered that the mice treated with integrin αV inhibitors Cilengitide or SB273005 developed dramatically expansive ascending TAA, accompanied by exacerbated disorganization or loss of elastic fibers. Bulk RNA sequencing results further indicated that the treatment with integrin αV inhibitors exacerbates the pro-inflammatory response in mouse TAA development. These data suggest that integrin αV may be a novel target for TAA intervention. However, it also raises concerns about exposure to integrin αV inhibitors, which are conducted in serious cancer clinical trials, may pose a potential risk of developing aortic aneurysm (AA)/AD.

overall_design: The smooth muscle cells (SMCs) isolated from mouse aorta were transfected with ITGAV silence RNA. Then the SMCs were stimulated by TGF-β or PDGFBB. Finally, the SMCs were harvested for bulk RNA sequencing.

first: Yuan

last: Zhu

first: Zhanzeng

last: Feng

first: Zhanglong

last: Hu

first: Jixie

last: Le

first: Chao

first: Jian

last: Shen

first: Shiyu

first: Shuang

last: Wu

first: Hong

last: Ma

first: Meixiang

last: Xiang

first: Yao

last: Xie


title: Integrin αV as a potential target in aortic aneurysm and dissection

overall_design: The ascending TAA tissues of mice fed with BAPN and integrin αV inhibitors Cilengitide or SB273005 were harvested for bulk RNA sequencing.

last: Chen


title: DOT1L provides transcriptional memory through PRC1.1 antagonism [ChIP-Seq]

city: Melbourne

first: Daniel

last: Neville

state: Victoria

address: 99 Commercial Road Level 6, Alfred Centre

department: Australian Centre for Blood Diseases

country: Australia

institute: Monash University

summary: DOT1L and Menin are essential cofactors for the oncogenic activity of MLL-fusion proteins (MLL-FPs) in leukaemia. However, the mechanisms underpinning the therapeutic effects of their inhibitors remain unclear. Here, we identify a critical role for the non-canonical Polycomb repressive complex 1.1 (PRC1.1) in mediating the cellular responses to DOT1L and Menin inhibitors. Menin inhibition induces PRC1.1-dependent deposition of H2AK119ub to silence a subset of MLL-FP targets, whereas DOT1L inhibition results in a genome-wide increase in H2AK119ub. We show that enhanced PRC1.1 activity arises specifically from the progressive loss of DOT1L-mediated H3K79 methylation, independent of MLL-FP displacement or transcriptional repression. This regulatory crosstalk is conserved across cell types and is driven by direct biochemical antagonism between H3K79 methylation and PRC1.1 activity. Together, our findings establish DOT1L as a component of transcriptional memory co-opted in leukaemia and suggest it serves as the missing link balancing the opposing forces of the MLL-Polycomb system.

overall_design: ChIP sequencing of AML cell lines (murine FLAG-MLLAF9 and MOLM13) and K562 cells with and without DOT1L or Menin inhibitor treatment. ChIP-sequencing of HuDEP-2 (human erythroid progenitors) and murine embryonic stem cells with and without DOT1L inhibitor treatment.

first: Omer

last: Gilan


title: VEGFA Stop-gained Variant Deteriorates Cardiac Remodeling in Myocardial Infarction [RNA-seq]

first: Zhongxiang

address: 浦东新区东方路1678号上海儿童医学中心

first: Min

last: Zhang


title: TL1A drives ILC-mediated granulopoiesis and colitis associated cancer

city: New York

first: Silvia

last: Pires

address: 413E 69th st

institute: Weill Cornell Medicine

summary: The incidence of colorectal cancer (CRC) is increased in patients with ulcerative colitis (UC) and accounts for up to 15% annual mortality in patients with inflammatory bowel disease (IBD). Variants in TNFSF15, the gene that encodes TL1A, are associated with more aggressive IBD and advanced CRC. Here, we show that TL1A signaling is required for colitis-associated tumorigenesis and sufficient to promote CRC in mouse models. TL1A signaling in group 3 innate lymphoid cells (ILC3) promotes GM-CSF dependent activation of colonic neutrophils and colitis-associated tumors in mouse models. TL1A-mediated, ILC3-dependent tumor-associated neutrophil (TAN) signatures were evident in mouse models and reduced in subjects with UC treated with anti-TL1A therapy. Furthermore, TL1A promoted ILC-dependent emergency granulopoiesis, which is similarly evident in IBD subjects with TNFSF15 risk variants. These results reveal a new mechanism by which TL1A signaling in tissue resident ILCs shape TANs and emergency granulopoiesis with the potential to guide emerging anti-TL1A therapies for IBD.

overall_design: To determine the impact of TL1A-dependent inflammation on neutrophils, we performed RNA-sequencing of bone marrow-derived neutrophils cultured with supernatants from TL1A- unstimulated or stimulated ILC3s. For RNA-sequencing of bone marrow derived neutrophils 1x105 cells were stimulated for 18h with ILC3s supernatants, and 2×103 of sort-purified intestinal ILC3s were unstimulated or stimulated for 18h with either IL-23 or TL1A


title: Urotensin II Activates Sensory-cutaneous Pathway to Promote Itch and Cutaneous Inflammation

city: Kaifeng City, Henan Province

first: Hua

last: Yang

state: Henan Province

address: Jinming Campus of Henan University

institute: Henan University

summary: In order to study the effect of UII on the transcription level regulation of itch-related genes in sensory neurons and keratinocytes, and to apply UII in mouse dorsal root ganglion neuronal cells and keratinocytes, the study showed that UII significantly upregulated the expression of various characteristics of atopic dermatitis and itch-related genes, such as Fasl, Mrgprx1, Amy2a3, INHBA, IL36G, STEAP2, etc.

overall_design: To investigate the effect of UII activation on gene expression regulation in mouse dorsal root ganglion neuronal cells and human primary keratinocytes. RNA sequencing of 6 mouse dorsal root ganglion neuronal cell samples and 6 human keratinocytes samples. They were 3 UII-treated mouse dorsal root ganglion neuronal cell samples, 3 from untreated control group cells, in addition to 3 UII-treated human primary keratinocytes for 24 h and 3 cells from untreated control cells.

first: RenKai

first: Wenhao

first: Weiwei

first: Xinrong

last: Yan

first: Chunxu

last: Shan

first: Shanghai

last: Xue

first: Ruizhen

last: Wang

first: Xiaolong

last: Dai

first: Ciara

last: Larkin

first: Jiafu

first: Jianghui

last: Meng


title: NBL1 Correlates with Renal Phenotypes in Mouse Models of Kidney Disease, but is not Causal: Male Mice with XLAS either HET or WT for Nbl1

status: Public on Nov 22 2025

city: Bar Harbor

first: Courtney

last: Willey

state: Maine

address: 600 Main Street

institute: The Jackson Laboratory

summary: Background: Increased concentrations of neuroblastoma suppressor of tumorgenicity 1 (NBL1) in the blood have been associated with disease progression in diabetic kidney disease and IgA nephropathy. However, it is unclear whether NBL1 is a causal factor for kidney disease and what is driving these increased concentrations in the blood. Methods: We tested causality of NBL1 by knocking out Nbl1 in two different mouse models of kidney disease (X-linked Alport Syndrome (XLAS) and low-dose cisplatin treatment) and performed a genetic analysis for the drivers of NBL1 concentrations in two independent cohorts of genetically diverse (DO) mice with X-linked Alport Syndrome (DO-XLAS). Results: Significant correlations were found between NBL1 concentrations in the blood and both GFR and ACR in DO-XLAS mice. However, XLAS mice with only one functional Nbl1 allele and reduced NBL1 concentrations had similar GFR and ACR compared to Nbl1 wildtype animals. Similarly, there was no difference between animals with one or two functional Nbl1 alleles after chronic low-dose cisplatin treatment. Genetic analysis of NBL1 concentrations in our DO-XLAS cohorts identified associations with loci on Chromosomes 4 and 17, with Clcnka, and MHC2 as potential candidates. Conclusion: Increased NBL1 in blood is a marker for different forms of kidney disease but is not a causal factor.

overall_design: Male mice with XLAS either HET or WT for Nbl1 (all mice are on the B6 background). Bulk RNA-seq of kidneys collected at 15-weeks of age.

first: Rei

last: Bufi

first: Harsphpreet

last: Chandok

first: Ron

last: Korstanje


title: UHRF1 Deficiency Exacerbates Intestinal Inflammation by Epigenetic Modulation of NPY1R Gene Methylation

city: Xi'an

first: Xiaodi

last: Zhao

address: No.127 Changle West Road

department: Xijing Hospital of Digestive Diseases

institute: Xijing Hospital of Fourth Military Medical University

summary: Epigenetic modifications play a crucial role in the pathogenesis of inflammatory bowel disease (IBD) by mediating gene–environment interactions. We previously showed that UHRF1, a central regulator of DNA methylation, contributes to cancer progression; however, its function in IBD remains poorly understood. Here, we revealed that UHRF1 is frequently reduced in inflamed tissues of IBD patients and that its deficiency exacerbates intestinal epithelial cell (IEC) damage. Through a multi-level approach incorporating human cell models and an intestinal epithelial-specific Uhrf1 knockout mouse model, we established UHRF1 as a key mitigator of IBD progression. Mechanistically, UHRF1 bound to the NPY1R promoter, promoting its methylation and leading to transcriptional suppression. The NPY1R upregulation resulting from UHRF1 deficiency attenuated cAMP–PKA–CREB signaling in IECs, thereby enhancing NF-κB activation and subsequent pro-inflammatory responses, which compromised intestinal epithelial barrier integrity. Furthermore, we identified miR-141 as a negative regulator of NPY1R, highlighting its potential as a therapeutic agent. Collectively, our results identified the UHRF1–NPY1R regulatory axis as a critical epigenetic mechanism in intestinal inflammation and underscored its dual promise for IBD diagnostics and therapy.

overall_design: Genomic DNA was isolated from NCM460-shCtrl and NCM460-shUHRF1 cells using the QIAamp DNA Mini Kit (Qiagen). DNA purity and concentration were measured with a Nanodrop 2000 spectrophotometer (Thermo Scientific). Approximately 500 ng of DNA from each sample was subjected to sodium bisulfite conversion using the EZ DNA Methylation-Gold Kit (Zymo Research) according to the manufacturer’s protocol. Genome-wide DNA methylation was assessed using the Illumina Infinium HumanMethylation850K BeadChip (Illumina) following the manufacturer’s instructions. Array data (IDAT files) were analyzed with the ChAMP package in R to determine methylation levels. The methylation status of each probe was represented as a β value, defined as the ratio of methylated probe intensity to total probe intensity (sum of methylated and unmethylated intensities plus a constant α, α = 100). CpG sites with |Δβ| ≥ 0.20 (test vs. control) and an adjusted P value ≤ 0.05 were considered differentially methylated. A CpG site was classified as hypermethylated if Δβ ≥ 0.20 or hypomethylated if Δβ ≤ −0.20.

first: Han

last: Yanan


title: UHRF1 Deficiency Exacerbates Intestinal Inflammation by Epigenetic Modulation of NPY1R Gene Methylation [gene expression]

overall_design: gene expression in NCM460-shCtrl and NCM460-shUHRF1 cells was measured

first: Bai


title: The proportional scaling of mRNA and ribosome concentrations controls eukaryotic cell growth [Ribo-seq]

city: Stanford

first: Xin

last: Gao

state: California

address: 327 Campus Drive

department: Department of Biology

institute: Stanford univerisity

summary: Cell growth underlies nearly all eukaryotic physiology, yet its quantitative principles remain unclear. Using single-molecule ribosome tracking, spike-in RNA sequencing, and quantitative proteomics across 15 nutrient-limited conditions in budding yeast, we define how growth is controlled in the budding yeast Saccharomyces cerevisiae. Ribosome concentration scales linearly with growth rate, while peptide elongation speed remains constant at ~9 amino acids s⁻¹, implying elongation is not a regulatory lever as in bacteria. Instead, total mRNA concentration increases proportionally with ribosomes to accelerate growth. A simple kinetic model of mRNA–ribosome binding accurately predicts the fraction of active ribosomes, growth rate, and responses to transcriptional or size perturbations. Consistent with this model, transient inhibition of mRNA degradation boosts growth by elevating mRNA concentration. These results reveal that eukaryotic cells accelerate proliferation primarily by proportionally scaling mRNA and ribosome abundance, establishing a quantitative framework for understanding eukaryotic biosynthesis.

overall_design: This project profiles transcription and translation in Saccharomyces cerevisiae across four defined growth conditions. We generated spike-in RNA-seq datasets to quantify absolute (per-cell) total mRNA concentration and to assess global transcriptome changes with internal standards. In parallel, ribosome profiling (Ribo-seq) was performed to map ribosome-protected footprints and estimate gene-specific translation efficiency by relating footprint density to mRNA abundance. Together, these paired datasets provide a resource to dissect how gene expression is allocated between transcription and translation under distinct conditions.

first: Jan

last: Skotheim


title: The proportional scaling of mRNA and ribosome concentrations controls eukaryotic cell growth [Spike-in_RNAseq]


title: The highly localized interaction between Neurofascin-186 and Gliomedin promotes subcellular innervation by the chandelier cell

city: Columbus

first: Hiroki

last: Taniguchi

state: OH

address: 333 W 10th Ave

department: Department of Neuroscience

institute: Ohio State University

summary: A variety of cortical inhibitory interneuron (IN) subtypes differentially but coordinately operate in local circuits to process neuronal signals. The subcellular arrangement of IN synaptic outputs contributes to subtype-specific functional specialization. However, it remains poorly understood what intercellular molecular interactions enable the matched synapse formation between IN subtypes and specific subcellular domains. Using mice of both sexes, we demonstrate that Neurofascin-186 (NF186), a cell adhesion molecule specifically expressed in the axon initial segments (AISs) of pyramidal neurons, is necessary for chandelier cells (ChCs) to develop a string of synaptic boutons along the AIS (an axon cartridge). Furthermore, we discovered that Gliomedin, a known receptor for NF186 in the nodes of Ranvier, is preferentially expressed in ChCs and mediates ChC axon cartridge development by acting as a major receptor for NF186. Thus, the intercellular interaction through subcellularly-restricted ligands and cell type-specific receptors ensures a high degree of IN subcellular synapse specificity.

overall_design: RNAseq profiling of cortical interneuron subtypes extracted from postnatal day 5 VIP-Cre;Ai47, SOM-Cre;Ai47, Nkx2.1-CreER;Ai47 mice

first: Yugo

last: Ishino

first: Yasufumi

last: Hayano

first: Gogce

last: Crynen


title: A screen-identified immunomodulator protects against Staphylococcus aureus infection via the VCP-PERK-Nrf2 signaling axis

city: Houston

first: Liyang

last: Zhang

state: TX

address: 6670 Bertner Ave

department: Department of Medicine

institute: Houston Methodist Research Institute

summary: Antibiotic resistance threatens the effectiveness of conventional antimicrobials, underscoring the need for host-directed therapies that enhance immune defense. Here, we present a cross-species discovery pipeline that couples a Caenorhabditis elegans–Staphylococcus aureus infection screen with mammalian mechanistic validation to identify small-molecule immunomodulators. Using six C. elegans innate immunity reporter strains, we identified SKI-II as a previously unrecognized host-protective compound that activates the SKN-1/Nrf2 oxidative-stress pathway to protect worms from S. aureus infection without directly killing the pathogen. In mammalian RAW264.7 macrophages, we found that SKI-II binds to the ATPase pocket of VCP (Valosin-Containing Protein), establishing a VCP–PERK (PRKR-like Endoplasmic Reticulum Kinase)–Nrf2 signaling axis that reduces the levels of pathogenic ROS (reactive oxygen species). PERK activation also promotes macrophage M1 polarization and a metabolic shift from oxidative phosphorylation to glycolysis, reducing mitochondrial ROS production. This work identifies VCP as a druggable node for host-directed immunomodulation and identifies SKI-II as a prototype small molecule that boosts host tolerance to infection, validating a C. elegans-based screening approach as a platform for discovering immunomodulators active in mammalian systems.

overall_design: RNA-seq profiling was performed on murine macrophage RAW264.7 cells treated with 4 μg/mL SKI-II or an equivalent volume of DMSO (control) for 24 hours. Differential gene expression analysis was conducted between the two groups.


title: The proportional scaling of mRNA and ribosome concentrations controls eukaryotic cell growth [Spike-in_gDNAseq]

overall_design: This project profiles transcription and translation in Saccharomyces cerevisiae across four defined growth conditions. We generated spike-in RNA-seq datasets to quantify absolute (per-cell) total mRNA concentration and to assess global transcriptome changes with internal standards.


title: Multi-drug tolerance in Leishmania persister-like cells

city: Antwerp

first: Pieter

last: Monsieurs

address: Nationalestraat 155

country: Belgium

institute: Institute of Tropical Medicine

summary: Leishmaniasis is caused by parasitic protozoa of the genus Leishmania and is found widely across the tropics and sub-tropics, afflicting hundreds of thousands of people. The disease is notoriously difficult to treat. Here, we present evidence of the existence of persister-like cells in cultured Leishmania populations, induced upon exposure to normally lethal doses of antimony, a widely used anti-leishmanial.  Persisters are a small fraction of non-proliferative cells with reduced metabolism that are adapted to withstand a variety of environmental assaults, including lethal doses of antimicrobials. We show that Leishmania persister-like cells survive lethal doses of antimonials by adopting a quiescence phenotype characterised by reduced proliferation, constrained metabolism, and diminished mitochondrial membrane potential. What is more, these cells demonstrate cross-tolerance to other anti-leishmanial drugs. Wild-type persister-like cells reverted to similar levels of drug susceptibility once the antimony-induced pressure was removed. Surprisingly, cells which had previously been selected for genetic changes causing resistance to antimony acquired a level of hyper-resistance after transient passage through the quiescent state, without further genetic change. Our results demonstrate the extreme versatility of this eukaryotic pathogen in adaptation to drug pressure and highlight the need for the development of new anti-leishmanials targeting non-proliferative forms.

overall_design: bulk RNA-seq analysis of PAT exposed Leishmania donovani cells. RNA is extracted at Day 0, Day2, Day 4 and after PAT pressure, for both strains BPK026 and BPK275.

first: Allison

last: Aroni-Soto

first: Odin

last: Goovaerts

first: Kaoutar

last: Choukri

first: Basudha

last: Khanal

first: Wim

last: Adriaensen

first: Jean-Claude

last: Dujardin

first: Michael P

last: Barrett

first: Malgorzata A

last: Domagalska


title: Multiomic Profiling of the Liver Across Diets and Age in a Diverse Mouse Population

city: Memphis

first: Robert

last: Williams

state: TN

address: 71 South Manassas

department: Genetics Genomics and Informatics

summary: We profiled the liver transcriptome, proteome, and metabolome from 347 individuals from 58 isogenic strains of the BXD mouse population across age (7 to 24 months) and diet (low or high fat) to link molecular variations to metabolic traits. Several hundred genes are affected by diet and/or age at the transcript and protein levels. Orthologs of two aging-associated genes, St7 and Ctsd, were knocked down in C. elegans, reducing longevity in wildtype and mutant long-lived strains. The multiomics data were analyzed as segregating gene networks according to each independent variable, providing causal insight into segregating edges. Candidate hits were cross-examined in an independent Diversity Outbred mouse liver dataset segregating for similar diets, with ~80-90% of diet-related candidate genes found in common across datasets. Together, we have developed a large multiomics resource for multivariate analysis of complex traits and demonstrate a methodology for moving from observational associations to causal connections.

overall_design: RNA sequencing. About the cases used to generate this set of data: All animal care was handled according to the NIH's Guidelines for the Care and Use of Laboratory Animals and was also approved by the Animal Care and Use Committee of the University of Tennessee Health Science Center (UTHSC). 2157 mice from 89 strains of the BXD family (including parents and both F1s) were followed in the colony. 159 animals were males and 1998 animals were females. Animals were maintained in the UTHSC vivarium in Specific Pathogen-Free (SPF) housing throughout the longevity experiment. The housing environment was a 12-hour day/night cycle in 20–24°C temperature with housing cages of 145 in2 with up to 10 animals per cage. Diets were either Harlan Teklad 2018 (CD; 24% calories from protein, 18% from fat, 58% from carbohydrates) or Harlan Teklad 06414 (HFD; 18.3% calories from protein, 60.3% from fat, 21.4% from carbohydrates). Water was Memphis city municipal tap water. Food and water were ad libitum. All animals were followed from their point of entry into the colony (typically around 5 months of age) until death. Animals were checked daily for morbidity and were weighed approximately every 2-3 months throughout their lives. 662 animals were sacrificed at specific ages for tissue collection across cohort (i.e. diet, strain, sex, and age). These 662 animals were selected for tissue harvest with the following aims: 2 animals per strain, diet, and age, for a target of 4 age points, i.e. up to a target maximum of 16 sacrificed animals per strain (2 replicates * 2 diets * 4 ages). Transcriptomics were acquired for 291 individuals, which had targeted data generation for 1 animal of each of the 309 cohorts (i.e of the 662 individuals, just over half had a biological replicate which was age, diet, strain, and sex-matched). The target ages were 7, 12, 18, and 24 months of age. Roughly every 3 months for the duration of the experiment, ~40 animals were selected for sacrifice, with approximately 15 animals sacrificed per day over the course of 3 or 4 continuous days. Animals were removed from the aging colony the night prior to sacrifice, but retained access to food and water.

first: Evan G

first: Niklas

last: Pfister

first: Suheeta

last: Roy

first: Cyril

last: Statzer

first: Jack

last: Haverty

first: Jesse

last: Ingels

first: Casey

last: Bohl

first: Moaraj

last: Hasan

first: Jelena

last: Cuklina

first: Peter

last: Buhlmann

first: Nicola

last: Zamboni

first: Lu

last: Lu

first: Collin Y

last: Ewald

first: Robert W

first: Ruedi

last: Aebersold


title: DOT1L provides transcriptional memory through PRC1.1 antagonism [RNA-seq]

first: Daniel

last: Neville

overall_design:
3'RNA sequencing of MOLM13, MV4;11, murine MLLAF9, K562, mESC, HuDEP-2 cells with and without DOT1L and/or Menin inhibitor treatment in control or PCGF1, BCOR KO. RNA-seq experiments were conducted in triplicate.

RNA sequencing of AML cell lines with and without DOT1L or Menin inhibitor treatment. RNA-seq experiments were conducted in triplicate.

first: Omer

last: Gilan


title: Intestinal interoceptive dysfunction drives age-associated cognitive decline [cohousing]

city: Palo Alto

first: Christoph

last: Thaiss

state: CA

address: 3181 Porter Dr.

department: Immunology and Pathology

institute: Arc Institute

summary: Aging is accompanied by declining memory function, necessitating the development of effective countermeasures1. Brain- extrinsic factors influencing cognitive decline, including the intestinal microbiome, have emerged as attractive targets for peripheral interventions2-6, but the underlying mechanisms remain largely unclear. Here, by charting a high-resolution map of microbiome aging and its functional consequences throughout the lifespan of mice, we identify a mechanism whereby age- associated inhibition of gut-brain signalling results in impaired novelty-induced neuronal activation in the hippocampus and loss of memory encoding. Specifically, gut bacteria producing medium-chain fatty acids, such as Parabacteroides goldsteinii, accumulate over the lifespan and drive intestinal myeloid cell inflammation through GPR84 signalling. As a result, the function of afferent gut-innervating vagal neurons is impaired, the interoceptive signal received by the brain is weakened, and hippocampal function declines. We leverage this pathway to define interventions that restore memory in aged mice, such as phage targeting of Parabacteroides, GPR84 inhibition, and restoration of vagal activity. These findings indicate a key role for interoceptive signalling from the gastrointestinal tract in regulating brain aging and suggest that interoceptomimetics that stimulate gut-brain communication may counteract age-associated cognitive decline.

overall_design: 16s microbiome sequencing of mice with fecal microbiome transplant from either young mice or old mice with associated inputs as a control

first: Timothy

last: Cox

first: Ashwarya

last: Devason

first: Sydney

last: Mason

first: Madhav

last: Subramanian

first: Andrea

last: Salvador

first: Helene

last: Descamps

first: Alan

last: Araujo

first: Junwon

last: Kim

first: Yixuan

last: Zhu

first: Lev

last: Litichevskiy

first: Sunhee

last: Jung

first: Wondsuk

last: Song

first: Adrian

last: Martin

first: Nathan

last: Henderson

first: Kuei-Pin

last: Huang

first: Thao

last: Nguyen

first: Wisath

last: Sae-Lee

first: Iboro

last: Umana

first: Maria

last: Sacta

first: Ryan

last: Rahman

first: Stephen

last: Wisser

first: Andrew

last: Nelson

first: Ilona

last: Golynker

first: Lenka

last: Dohnalova

first: Alana

last: McSween

first: Eric

last: Hohmann

first: Shaan

last: Patel

first: Anna

last: Bub

first: Clara

last: Sanchez

first: Kevt'her

last: Hoxha

first: Lavinia

last: Boccia

last: Wong

first: Klaas

last: Bahnsen

first: Jihee

last: Blank

first: Dina

last: Abbasian

first: Clarissa

last: Shoffler

first: Christopher

last: Petucci

first: Fiona

last: McAllister

first: Amber

last: Alhadeff

first: Marc

last: Fuccillo

first: Colin

last: Hill

first: Cholsoon

last: Jang

first: Nicholas

last: Betley

first: Guillaume

last: de Lartigue

first: Virginia


title: Intestinal interoceptive dysfunction drives age-associated cognitive decline [RNA-Seq]

first: Christoph

last: Thaiss

first: Timothy

last: Cox

first: Ashwarya

last: Devason

first: Sydney

last: Mason

first: Madhav

last: Subramanian

first: Andrea

last: Salvador

first: Helene

last: Descamps

first: Alan

last: Araujo

first: Junwon

last: Kim

first: Yixuan

last: Zhu

first: Lev

last: Litichevskiy

first: Sunhee

last: Jung

first: Wondsuk

last: Song

first: Adrian

last: Martin

first: Nathan

last: Henderson

first: Kuei-Pin

last: Huang

first: Thao

last: Nguyen

first: Wisath

last: Sae-Lee

first: Iboro

last: Umana

first: Maria

last: Sacta

first: Ryan

last: Rahman

first: Stephen

last: Wisser

first: Andrew

last: Nelson

first: Ilona

last: Golynker

first: Lenka

last: Dohnalova

first: Alana

last: McSween

first: Eric

last: Hohmann

first: Shaan

last: Patel

first: Anna

last: Bub

first: Niklas


title: A novel interferon stimulated gene GALNT2 is required to restrict respiratory virus infections

city: Guangzhou

first: fenghua

last: chen

address: 195 Dongfengxi Road, Yuexiu District

institute: Guangzhou Medical University

summary: Respiratory viruses, particularly coronaviruses (CoVs) and influenza A viruses (IAVs), have driven global pandemics, with zoonotic spillover posing ongoing threats to public health. SARS-CoV-2, the cause of COVID-19, emerged in 2019, devastating global health and claiming over 7 million lives, while the 2009 influenza pandemic caused at least 200,000 deaths. The innate immune system serves as the first line of defense, where type I interferons (IFNs) and interferon-stimulated genes (ISGs) play pivotal antiviral roles. Impaired IFN-I responses are linked to severe COVID-19 and influenza, underscoring their importance: life-threatening COVID-19 cases often involve genetic defects in IFN pathways or neutralizing autoantibodies that dampen IFN activity, whereas children’s resilience to severe infection correlates with robust IFN responses. Recombinant IFNs show therapeutic potential, though timing is critical. Key ISGs like OAS1 and OASL further illustrate IFN-mediated protection, highlighting the need to dissect how individual ISGs aid viral clearance and mitigate disease. In this context, we identified GALNT2, an O-GalNAc transferase, as a novel ISG that enhances viral clearance and reduces susceptibility and severity in both SARS-CoV-2 and IAV infections.

overall_design: RNA sequencing was performed on A549 cell lines with or without GALNT2 overexpression, with three biological replicates for each experimental condition


title: Interferon signaling underlies radiotherapy responses in malignant peripheral nerve sheath tumors (MPNSTs)

city: San Francisco

first: Iowis

last: Zhu

address: 1450 3rd Street, HD449

institute: University of California, San Francisco

summary: The clinical significance of specific genetic alterations, methylation signatures or microenvironmental composition in malignant peripheral nerve sheath tumors (MPNSTs) is unclear. We assembled an updated cohort of 30 patients with MPNSTs treated with surgical resection and postoperative radiation who underwent methylation profiling and detailed clinical follow-up. The data included in this submission include 7 of 30 samples, the remainder of which were submitted separately under GSE212963.

overall_design: We correlated tumor methylation data with detailed clinical followup for 30 patients with MPNSTs who had been treated with post-operative radiation therapy.

first: Kanish

last: Mirchia

first: Harish

last: Vasudevan


title: Intestinal interoceptive dysfunction drives age-associated cognitive decline [16S fmt]

first: Christoph

last: Thaiss

first: Timothy

last: Cox

first: Ashwarya

last: Devason

first: Sydney

last: Mason

first: Madhav

last: Subramanian

first: Andrea

last: Salvador

first: Helene

last: Descamps

first: Alan

last: Araujo

first: Junwon

last: Kim

first: Yixuan

first: Lev

last: Litichevskiy

first: Sunhee

last: Jung

first: Wondsuk

last: Song

first: Adrian

last: Martin

first: Nathan

last: Henderson

first: Kuei-Pin

last: Huang

first: Thao

last: Nguyen

first: Wisath

first: Clara

last: Sanchez

first: Kevt'her

last: Hoxha

first: Lavinia

last: Boccia

last: Wong

first: Klaas

last: Bahnsen

first: Jihee

last: Blank

first: Dina

last: Abbasian

first: Clarissa

last: Shoffler

first: Christopher

last: Petucci

first: Fiona

last: McAllister

first: Amber

last: Alhadeff

first: Marc

last: Fuccillo

first: Colin

last: Hill

first: Cholsoon

last: Jang

first: Nicholas

last: Betley

first: Guillaume

last: de Lartigue

first: Virginia


title: Distinct immunomodulatory pathways mediate radiotherapy response in malignant peripheral nerve sheath tumors [sgRNA library]

first: Iowis

last: Zhu

summary: We performed a genome-wide CRISPRi screen to identify potential contributors to radioresistance in the JH02.2 malignant peripheral nerve sheath tumor (MPNST) cell line.

overall_design: We transduced a barcoded lentiviral sgRNA library into a JH-2-002 human MPNST cell line expressing dCas9-Zim3, with virus titrated to approximate 1 sgRNA per cell. Cells were sorted for library expression using FACS, and a T0 control was collected at Day 0. Two experimental groups were designed, with one receiving 2 daily fractions of 2 Gy and the other being untreated, receiving no radiation. Genomic DNA (gDNA) from all cells was harvested at Day 10 and sgRNA barcodes were amplified and sequenced.

first: Julien

last: Chien

first: Sixuan

last: Pan

first: Harish

last: Vasudevan


title: A single-nucleus dataset sampling subcutaneous white adipose from living donors to study familial partial lipodystrophy 2

city: Ann Arbor

first: Bioinformatics

last: Core

state: MI

address: BRCF Bioinformatics Core, 2800 Plymouth Rd

institute: University of Michigan

summary: Familial partial lipodystrophy 2 (FPLD2) is a rare disease characterized by adipose tissue loss and redistribution, and metabolic dysfunction. FPLD2 is caused by pathogenic variants in the LMNA gene, encoding nuclear lamins A/C, structural proteins that control nuclear function and gene expression. However, the mechanisms driving adipocyte loss in FPLD2 remain poorly defined. In this study, we recruited eight families with developing or established FPLD2 and performed clinical, histological, and transcriptomic analyses of subcutaneous adipose tissue biopsies. Bulk and single-nuclei RNA-sequencing revealed suppression of lipid metabolism and mitochondrial pathways, alongside increased inflammation. These signatures were mirrored in tamoxifen-inducible adipocyte-specific Lmna knockout mice, in which lamin A/C-deficient adipocytes shrank and disappeared. Lmna-deficient fibroblasts shared similar gene expression changes, linked to altered chromatin accessibility, underscoring lamin A/C’s potential regulatory role in lipid metabolism and inflammatory programs. By directly comparing atrophic and hypertrophic adipose depots in FPLD2, and integrating human, mouse, and in vitro models, this study provides new insights into disease progression and potential therapeutic targets.

overall_design: Single nuclei RNA-seq of human subcutaneous white adipose tissue surgical biopsies from patients with developing FPLD2, developed FPLD2, or control unaffected patients, either from the abdomen or dorsocervical region (upper neck)

first: Jessica

middle: N

last: Maung

first: Akira

last: Nishii

first: Rebecca

last: Schill

first: Ormond

last: MacDougald


title: Distinct immunomodulatory pathways mediate radiotherapy response in malignant peripheral nerve sheath tumors [scRNA-Seq]

summary: We used single-cell RNA-sequencing (scRNA-seq) to study the effect of ionizing radiation on the transcriptomes of malignant peripheral nerve sheath tumors (MPNSTs) in vivo and in the context of the innate and adaptive immune response.

overall_design: We subcutaneously implanted immunocompetent C57/B6 mice with the JW23.3 MPNST cell line at Day 0. On Day 7, mice were randomized into two experimental groups based upon tumor size and one group was focally irradiated at the site of tumor implantation with 5 daily fractions of 2 Gy. At Day 21, tumors were harvested and processed for scRNA sequencing using manufacturer's instructions (Chromium Next GEM Single Cell 3’ GEM, Library & Gel Bead Kit v3.1) for the Illumina 10X platform. We used these data to compare the transcriptomes of tumor and host cells in tumors that had and had not received irradiation.


title: CRISPR Screen Reveals SOX2 as a Critical Regulator of CD133 and Cellular Stress Response in Glioblastoma

city: Hamilton

first: Sheila

last: Singh

state: ON

address: 1280 Main Street West

department: Biochemistry and Biomedical Sciences

institute: McMaster University

summary: Looking for transcriptional differences between CD133 positive brain tumour initiating cells and CD133 negative brain tumour initiating cells and normal neural stem cells.

overall_design: Brain tumour initiating cells and normal neural stem cells were grown in vitro. Cells were flow sorted into CD133- and CD133+ populations using a CD133 antibody. Total RNA was isolated from the sorted cells using the QIAGEN RNEasy Kit.


title: B cell stimulation changes the structure and higher-order organization of the inactive X chromosome

city: Philadelphia

first: Montserrat

last: Anguera

state: PA

address: 3800 Spruce Street, Rosenthal Room 390EB

department: Biomedical Sciences

institute: University of Pennsylvania School of Veterinary Medicine

summary: X Chromosome Inactivation (XCI) equalizes X-linked gene expression between sexes. B cells exhibit dynamic XCI, with Xist RNA/heterochromatic marks absent on the inactive X (Xi) in naive B cells but returning following mitogenic stimulation. The impact of dynamic XCI on Xi structure and maintenance was previously unknown. Here, we find dosage compensation of the Xi with state-specific XCI escape genes in naive and in vitro activated B cells. Allele-specific OligoPaints indicate similar Xi and Xa territories in B cells that are less compact than in fibroblasts. Allele-specific Hi-C reveals a lack of TAD-like structures on the Xi of naive B cells, and stimulation-induced alterations in TAD-like boundary strength independent of gene expression. Notably, Xist deletion in B cells changes TAD boundaries and large-scale Xi compaction. Altogether, our results uncover B cell-specific Xi plasticity which could underlie sex-biased biological mechanisms.

overall_design: To determine how Xist deletion impacts transcriptional changes in splenic follicluar B cells, we sorted CD23+ splenic B cell subsets from female C57/BL6 WT and Xist cKO mice. We stimulated some follicular B cells with the TLR9 agonist CpG in vitro for 24 hours. We performed RNA sequencing naive and CpG-stimulated splenic follicular B cells with at least n=3 biological replicates per experimental group.

first: Isabel

last: Sierra

first: Natalie

middle: E

last: Toothacre

first: Robin

middle: H

last: van de Weide

first: Claudia

middle: D

last: Lovell

first: Son

last: Nguyen

first: R

middle: J

last: Varnett

first: Ashley

last: Cook

first: Han-Seul

last: Ryu

first: Sarah

last: Pyfrom

first: Harrison

last: Wang

first: Daniel

last: Beiting

first: Jennifer

last: Philips-Cremins

first: Eric

last: Joyce


title: Clonal T cell responses in human xenograft rejection

first: Ramin

last: Herati

state: New York

address: 430 E. 29th Street, 1st floor, room 135A-C

institute: NYU School of Medicine

summary: Despite the life-saving successes of solid organ transplantation, the number of individuals needing organ transplant far exceeds the number of organs available for use each year. Porcine xenotransplantation, or the use of pig organs for transplantation in people, holds substantial promise but xenograft rejection in humans is poorly understood. T cell rejection by the host immune system is a major challenge for human allografts and may limit the longevity of porcine xenografts. To study the xenograft rejection, we evaluated T cell responses and repertoire dynamics across tissues following porcine xenograft transplantation in a decedent model over 61 days after bilateral native kidney nephrectomy. Despite induction with anti-thymocyte globulin and ongoing  immune suppression consisting of rituximab, corticosteroids, calcineurin inhibition, and proliferation inhibition, human T cell infiltration of the xenograft was observed and was associated with xenograft dysfunction. Longitudinal analysis of T cell clonotypes in biopsies of the xenokidney revealed accumulation of clonal human CD4 and CD8 T cell responses. Moreover, circulating activated T cells, including circulating T follicular helper (cTfh), were xeno-reactive and increased in frequency around rejection events. A single CD8 clonotype dominated in the circulation leading up to the acute cellular rejection event. Following re-treatment with anti-thymocyte globulin and intensification of corticosteroids, the xeno-reactive T cell clonotypes were dramatically diminished in frequency in lymph nodes, though not eliminated. Together, these data demonstrate T cell repertoire dynamics across tissues in the setting of xenograft rejection and highlight opportunities for early surveillance and potential intervention.

overall_design: Multimodal single-cell RNA sequencing was used to compare T cells over time following porcine xenotransplantion in a decendent model.

first: Ekaterina

last: Novikova

first: Elizabeth

last: Severa

first: Fiorella

last: Chacon

first: Han

last: Chen

first: Farshid

last: Fathi

first: Nathan

last: Suek

first: Benjamin

last: Vermette

last: Bombardi

first: Eloi

last: Schmauch

first: Simon

last: Williams

first: Imad

last: Aljabban

first: Ian

middle: S

last: Jaffe

first: Karen

last: Khalil

first: Jacqueline

last: Kim

first: Elaina

middle: P

last: Weldon

first: Anoma

last: Nellore

first: Megan

last: Sykes

first: Adam

last: Griesemer

first: Brendan

last: Keating

first: Jeffrey

last: Stern

first: Robert

middle: A

last: Montgomery


title: Ectopic expression of MUC5B in the respiratory bronchiole initiates ER stress in the IPF lung

city: Denver

first: Rachel

last: Blumhagen

state: CO

address: 1400 Jackson St.

department: Center for Genes, Environment and Health

institute: National Jewish Health

summary: Subcellular spatial transcriptomics on lung tissue from idiopathic pulmonary fibrosis (IPF) and unaffected control subjects to further understand the pathogenesis of MUC5B-driven lung fibrosis.

overall_design: CosMxTM technology [CosMxTM Human Universal Cell Characterization RNA Panel (1000-plex) + 24 custom genes; Nanostring, USA] was applied to lung tissues from 15 IPF patients and 10 unaffected controls. 2 tissue microarrays were constructed from 25 FFPE tissue blocks, resulting 43 fields of view (FoVs). The following cell surface markers were used for morphology visualization: B2M/CD298, PanCK, CD45, CD3 antibodies and DAPI.

first: Ivana

last: Yang


title: Expression data from  OP- and OC- treated primary normal human epidermal keratinocytes (HEK).

city: Tsukuba,

first: Meriem

last: Bejaoui

address: 1 Chome-1-1 Tennodai

institute: University of Tsukuba

summary:
Oleuropein (OP) and Oleacein (OC) are enriched components in Olive (oil and leaves). However, their effects on skin have not been widely studied. Here, we perfomed global gene expression profiling to screen the potential effects of OP and OC on the skin. Results showed that OP and OC effectively regulated the key markers of differentiation. It suggested that olive-derived secoiriodids have the potential to support the skin barrier formation.
HEK cells were treated with 10ng/ml KGF, 200nM of OP and OC, respectively, for 96 hours under high calcium conditions to induce the differentiation. Microarray gene expression profiling was conducted biological triplicates.

overall_design: RNA was extracted using ISOGEN II (Nippon Gene Co. Ltd., Toyama, Japan). The integrity of RNA was quantified using NanoDrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). RNA samples were prepared for gene expression profiling analysis with GeneChip® 3' Expression Arrays using 3' IVT PLUS Reagent Kit (Affymetrix Inc., Santa Clara, CA, USA). Two hundred and fifty ng of total RNA from each sample was used to generate amplified and biotinylated complementary RNA (cRNA) from poly (A) RNA in a total RNA sample according to the user manual. IVT Incubation time was 16 hour. GeneAtlas® Hybridization, Wash and Stain Kit was used for hybridizing 3' IVT Array Strips according to the user manual (P/N 08-0306). The mouse genome array strips were hybridized for 16 hours in a 45oC incubator, washed and stained and finally imaging was done with the GeneAtlas Fluidics and Imaging Station.