title: DAB2IP modulates intestinal inflammation by enhancing ILC3 function in the gut

first: Zhiheng

last: He

address: 1450 Biggy Street NRT 5514 NRT 5514

department: Immunology and Immune Therapeutics

institute: University of Southern California

summary: Group 3 innate lymphoid cells (ILC3s) protect the intestinal barrier by producing IL-22 and IL-17A, yet the molecular mechanisms that sustain their cytokine output during inflammation remain poorly defined. Here, we identify the cytosolic scaffold DAB2IP as a critical ILC3-intrinsic regulator of effector function. In human IBD, DAB2IP expression is reduced in inflamed tissues, correlating with impaired epithelial repair and decreased IL-22. In mice, DAB2IP expression in ILC3s declines during intestinal inflammation, and silencing DAB2IP markedly diminishes IL-22 and IL-17A production. Adoptive transfer of Dap2ip-deficient ILC3s exacerbates DSS-induced colitis and increases susceptibility to Citrobacter rodentium. Mechanistically, DAB2IP promotes NF-κB activation, sustaining transcription of Il22 and Il17a. These results reveal a context-dependent role for DAB2IP as a positive regulator of NF-κB in ILC3s, highlighting its previously unknown function in mucosal immunity and epithelial repair, and suggesting that restoring DAB2IP signaling could enhance barrier protection during intestinal inflammation.

overall_design: Gene expression profiling analysis of RNA-seq data from MNK3_Scramble  and MNK3_sgDab2ip treated with IL-1β

first: Liang

last: Liu


title: Oncogenic LncRNA SLC16A1-AS1 Cooperates with NSUN2 to Stabilize GRP78 mRNA via m5C Modification in Gastric Cancer

status: Public on Feb 25 2026

city: Wenzhou

first: wenjing

last: zhao

address: Central North Road

country: China

institute: wenzhou medical university

type: Expression profiling by high throughput sequencing

summary: Long noncoding RNAs (LncRNAs) play crucial roles in regulating chromatin dynamics and gene expression, and their dysregulation is closely linked to tumorigenesis. However, their specific functions in gastric cancer (GC) remain poorly understood. Here, we found that LncRNA SLC16A1-AS1 was markedly overexpressed in GC through integrated RNA-seq analysis and validation in clinical tissues. High SLC16A1-AS1 expression correlated with advanced cancer stage, greater invasion depth, and poorer patient prognosis. Functional assays showed that SLC16A1-AS1 overexpression promoted GC cell proliferation, whereas knockdown inhibited proliferation in vitro and in vivo. Mechanistically, SLC16A1-AS1 interacted with the m5C methyltransferase NSUN2, enhancing m5C modification of GRP78 mRNA, which stabilized the transcript and increased GRP78 protein levels. Rescue experiments demonstrated that GRP78 overexpression reversed the proliferation-inhibitory effect of SLC16A1-AS1 depletion. These findings reveal that SLC16A1-AS1 drives GC cell proliferation via NSUN2-mediated m5C modification of GRP78 mRNA, suggesting a potential target for GC diagnosis and therapy.

overall_design: Gastric cancer tissues and adjacent non-cancerous tissues were collected from 80 patients undergoing GC resection at Nanjing First Hospital between 2013-2015. Tissues were immediately preserved in liquid nitrogen. m5C MeRIP-Seq were performed to profile m5C modifications.

first: Beiyao

last: Zheng

first: Wenjing

last: Zhao

first: Yan

last: Jin

first: Wentao

last: Sun

first: Yong

last: Li

first: Qi

last: Zhang

first: Yue

first: Jin

last: Wang

first: Dong

last: Chen

first: Ke

last: Ren

first: Wei

first: Yuanyuan

first: Li

last: Yuan

first: XueJun

first: Fen

last: Yang

first: Jinfei


title: SF3B1-K700E Drives Oncogenic Alternative Splicing of Cell Cycle Checkpoint Genes in Cancer

city: Jerusalem

first: Maayan

last: Salton

address: Ein-Kerem Canpus

country: Israel

institute: Hebrew University

summary: Pre-mRNA splicing plays a crucial role in maintaining cellular homeostasis, with strict regulation required for processes such as cell cycle progression. SF3B1, a core component of the spliceosome, has emerged as a key player in alternative splicing regulation and is frequently mutated in cancer. Among these mutations, SF3B1K700E disrupts normal splicing patterns and deregulates cell cycle control. In this study, we investigate the impact of SF3B1 phosphorylation on cell cycle-dependent splicing, with a particular focus on the checkpoint regulators ARPP19 and ENSA, two functionally related proteins that modulate PP2A-B55 activity during mitotic progression. Using RNA-seq analysis, we identify a subset of SF3B1-regulated splicing events that are enriched in cell cycle genes. We demonstrate that SF3B1 phosphorylation during G2/M promotes ARPP19-long isoform inclusion, a variant associated with poor survival in AML patients and accelerated mitotic exit. Notably, we show that inhibition of SF3B1 reverses the splicing changes induced by SF3B1K700E, reducing the levels of ARPP19-long and suggesting a potential therapeutic strategy for cancers with spliceosome mutations. Our findings highlight a direct link between SF3B1-dependent splicing, cell cycle progression, and tumorigenesis, providing new insights into the molecular mechanisms underlying cancer-associated splicing dysregulation.

overall_design: RNA-seq of three SF3B1-wt and three SF3B1-K700E mutant K562 cell samples

first: Mai

last: Baker

first: Eden

last: Engal

first: Aveksha

last: Sharma

first: Mayra

last: Petasni

first: Min-Hua

last: Su


title: Immunotolerant Oligomer Scaffolds Promote Regenerative Remodeling and Improved Muscle Structure and Function After Volumetric Muscle Loss

city: West Lafayette

first: Rachel

middle: A

last: Morrison

state: IN

address: 206 S Martin Jischke Dr

department: Weldon School of Biomedical Engineering

country: USA

institute: Purdue University

summary: Volumetric muscle loss (VML) overwhelms endogenous repair mechanisms, leading to defect contraction, fibrosis, and persistent aesthetic and functional deficits. Restorative biomaterials capable of re-establishing muscle structure and function represent promising strategies for treating severe injuries where conventional surgical repair is inadequate. Using a rat full-thickness VML model, we evaluated Oligomer, an engineered collagen polymeric biomaterial through spatial transcriptomic profiling. Spatial transcriptomic analyses defined a regenerative remodeling mechanism distinct from reparative or constructive remodeling, characterized by an immunotolerant environment that enabled infiltration of diverse progenitor populations, including pro-regenerative mesenchymal cells, pericytes, satellite cells, and endothelial and neural stem cells. This cellular niche supported coordinated activation of myogenic, vascular, and neural pathways, recapitulating key aspects of developmental myogenesis.

overall_design: Spatial transcriptomcs was performed on tibialis anterior (TA) muscles treated with Oligomer Scaffolds. Samples were harvested at 2 and 8 weeks post-treatment (n=2-4 per time point), bisected at the defect midline, and embedded in OCT for cryosectioning.  Samples were flash frozen in liquid nitrogen and stored at -80°C.

first: Joshua

last: Sexton

first: Lujuan

first: Eric

last: Dong

first: Hongyu

last: Gao

first: Yunlong

last: Liu

first: Stacey

last: Halum

first: Sherry

middle: L

last: Voytik-Harbin


title: Mislocalization of FTD3-Associated Mutant CHMP2B to the Nucleus of Human Neurons Due to Loss of a Nuclear Export Signal

city: Worcester

first: Evan

middle: Phillip

last: Hass

state: MA

address: 264 Plantation Street, LRB 560D

department: MCCB

institute: UMass Chan Medical School

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Frontotemporal dementia linked to chromosome 3 (FTD3) is caused by a splice site point mutation in CHMP2B, resulting in the production of mutant proteins CHMP2BIntron5 and CHMP2BΔ10. Here, we found that wildtype CHMP2B (CHMP2BWT) is mostly present in the cytoplasm, but CHMP2BIntron5 is mislocalized to the nucleus of human induced pluripotent stem cell (iPSC)-derived cortical neurons. To understand the underlying mechanism, we identified a previously unreported nuclear export signal (NES) in the C-terminus of CHMP2B. Functional assays, including CRM1 inhibition and site-directed mutagenesis of key hydrophobic residues, demonstrated that this NES motif is both necessary and sufficient for nuclear export of CHMP2BWT and ALS-associated CHMP2BQ206H, and its loss in CHMP2BIntron5 is responsible for the observed nuclear mislocalization. CHMP2BΔ10 remains in the cytoplasm due to the presence of an artificial NES in the C-terminus. These results reveal the presence of an NES in CHMP2B and highlight the need to dissect the gain-of-toxic nuclear functions of CHMP2BIntron5 in FTD3 pathogenesis.

overall_design: ATAC-seq was performed on 3-month-old iPSC-derived cortical neurons that were either wild type at the CHMP2B locus, heterozygous for the CHMP2B G26403C mutation, or homozygous for this mutation. Two different parental wild-type iPSC lines were used to generate the mutant lines. For one parental wild-type line, only a heterozygous mutant line was generated. For the second parental wild-type line, both heterozygous and homozygous mutant lines were generated.

first: Yong-Woo

last: Jun

middle: P

first: Thomas

middle: G

last: Fazzio

first: Fen-Biao


title: Identification of TBX5 Binding Sites in Mouse Embryonic Forelimbs

city: Athens

first: Douglas

last: Menke

address: 500 DW Brooks Drive

department: Genetics

institute: University of Georgia

summary: In order to identify putative regulatory targets of the TBX5 transcription factor, ChIP-Seq was performed on chromatin isolated from E10.5 mouse embryonic forelimb buds.

overall_design: ChIP-seq of mouse embryonic day 10.5 forelimbs against TBX5. Roughly 50 μg of sheared chromatin was isolated from E10.5 forelimb buds from outbred ICR mice (Envigo) and incubated with a TBX5 polyclonal antibody (R&D Systems AF5918). After isolation of antibody bound chromatin fragments with a Protein G Agarose Columns (Active Motif), libraries were prepared using the NEBNext Ultra II Library Prep Kit and amplified for 15 PCR cycles. Sera-Mag SpeedBeads were used to perform size selection  to remove primer and adapter fragments.

first: Aaron

last: Alcala


title: Early fibrotic niches establish tumour-permissive microenvironments

city: New York

first: Joo-Hyeon

last: Lee

address: 430 East 67th Street, New York, NY 10065, US

department: Developmental Biology

institute: Memorial Sloan Kettering Cancer Center

summary: Pathologic transformation represents a critical yet poorly defined window during which mutant epithelial stem cells actively construct the microenvironment that enables tumour initiation. Here, using integrated single-cell, spatial, and functional analyses, we define the earliest multicellular events that license this transition following oncogenic activation in the lung. KrasG12D-mutant alveolar type II cells rapidly adopt regenerative-like states that act as signalling hubs, orchestrating coordinated stromal and immune reprogramming while enhancing epithelial plasticity. Through secretion of Amphiregulin (Areg), mutant epithelial cells activate EGFR signalling in adjacent fibroblasts, inducing a fibrotic, injury-like programme. Reprogrammed fibroblasts, in turn, expand and reprogramme alveolar macrophages, amplifying inflammatory signalling and reinforcing epithelial plasticity. These reciprocal interactions establish a self-sustaining epithelial–stromal–immune circuit that generates a tumour-permissive niche prior to malignant outgrowth. Disruption of the Areg–EGFR axis prevents early niche formation and abrogates tumour initiation. Conservation of this programme in KRASG12D-inducible human alveolar organoids and early-stage lung adenocarcinoma tissues identifies epithelial–microenvironment communication as a therapeutically actionable vulnerability and suggests that intercepting niche formation may prevent progression to treatment-resistant disease.

overall_design: Human AT2 cell–derived lung organoids from healthy transplant donors were analysed under two conditions: SITTE11 (Control organoids) and SITTF11 (KRASG12D-transduced organoids). Single-cell RNA sequencing using the 10x Genomics Chromium platform was performed to compare gene expression profiles and identify early fibrotic niche formation and cross-compartmental remodelling induced by KRASG12D activation.

first: Jinwook

last: Choi


title: Vascular Basement Membrane Laminins Modulate  Functional Zonation of Cerebral Microvessels [RNA-seq]

city: Muenster

first: Lydia

last: Sorokin

address: Waldeyerstr. 15

country: Germany

institute: University of Muenster

summary: We investigated whether vascular basement membrane (BM) laminins influence vascular zonation by performing single-cell RNA sequencing (scRNAseq) on cerebral blood vessels from Lama4-/- mice - lacking the major vascular laminin 4 in endothelial and smooth muscle BMs - and wild-type littermates. Our dataset expands existing cerebral vascular transcriptomic profiles and reveals that Lama4-/- endothelial cells exhibit increased arterial marker expression and reduced postcapillary venule identity. In vitro and in vivo studies indicate that compensatory upregulation of laminin 5  in Lama4-/- vessels enhances expression of junctional proteins (Ocln, Cldn5) and promotes vessel contractility via increased expression of contractile genes in pericytes, which reside within the endothelial BM. Additionally, loss of Lama4 upregulates expression of large artery markers (Gja4, Dll4, Edn1,Tgfb2) and resulted in elevated autotaxin (Enpp2) levels, a key enzyme in lysophosphatidic acid production implicated in stroke. Accordingly, Lama4-/- mice exhibit worsened stroke outcomes, driven not by immune infiltration or junctional defects, but by increased vascular permeability likely mediated by autotaxin and/or activation of resident myeloid cells. Our data suggest that laminin 4/5 ratios in vascular BMs regulate functional zonation between arterioles, capillaries and postcapillary venules by modulating metabolic pathways in endothelial and mural cells, and indirectly influencing resident myeloid cells.

overall_design: Transient focal ischemia using the intraluminal filament model was performed on 12 week-old male mice. The left middle cerebral artery was occluded for 60 min and reperfusion was for 24h; ipsilateral (IL) brain hemispheres represent stroke samples and contralateral (CL) hemispheres were used as non-stroke controls.

first: Tushar

last: Deshpande


title: Breast Cancer Reveals Latent BMPR2-Related Susceptibility to Pulmonary Hypertension

city: Quebec city

first: Francois

last: Potus

address: 2725 Ch Ste-Foy

country: Canada

institute: IUCPQ-Laval university

summary: Background: Pulmonary arterial hypertension (PAH) and breast cancer disproportionately affect women. Bone morphogenetic protein receptor type 2 (BMPR2) mutations, the most common genetic cause of heritable PAH, also exert tumor-suppressive functions, yet their role in linking these diseases remains unclear. Methods: We combined bioinformatic, epidemiologic, and experimental approaches. Public cancer datasets were mined for BMPR2 alterations. In vivo, mammary tumor development and pulmonary hemodynamics were assessed in female Bmpr2⁺/Δ71 rats with or without carcinogen (DMBA) exposure. Pulmonary arterial smooth-muscle cells (PASMCs) were exposed to tumor-conditioned media to test inflammatory proliferation. Finally, associations between breast cancer and PAH were examined in the French National Healthcare Database (>9,000 PAH patients). Results: BMPR2 expression was markedly reduced in human breast tumors, with recurrent somatic variants and deep deletions identified. Bmpr2⁺/Δ71 rats exhibited spontaneous mammary tumors and, following DMBA exposure, developed exacerbated pulmonary hypertension with increased vascular remodeling and inflammation. Tumor-bearing Bmpr2⁺/Δ71 rats showed elevated lung IL-1β and NF-κB activation. In vitro, conditioned media from Bmpr2⁺/Δ71 tumors induced proliferation of Bmpr2⁺/Δ71 PASMCs via IL-1β-dependent signaling, while neutralization of IL-1β attenuated this effect. Human PASMCs carrying BMPR2 mutations similarly displayed heightened IL-1β-induced proliferation. Epidemiologically, breast cancer incidence was more than doubled in patients with PAH compared with the general population, and PAH incidence was increased nearly nine-fold among patients with breast cancer, indicating a bidirectional relationship. Conclusions: These findings identify a reciprocal association between breast cancer and PAH mediated by defective BMPR2 signaling and tumor-associated inflammation. Breast cancer may act as a “second hit” unmasking BMPR2-related susceptibility to PAH, underscoring BMPR2 as a shared molecular vulnerability with implications for surveillance of at-risk populations.

first: Victoria

last: Toro

first: Manon

last: Mougin


title: FUNCTIONAL ANALYSES OF HISTONE METHYLTRANSFERASES IN SEA LAMPREY EMBRYOS UNDERGOING PROGRAMMED DNA ELIMINATION

city: Lexington

first: Kaan Ihsan

last: Eskut

state: Kentucky

address: 195 Huguelet Dr.

department: Biology

institute: University of Kentucky

summary: During early embryogenesis, the sea lamprey Petromyzon marinus undergoes a dynamic form of genome rearrangement whereby several specific chromosomes are selectively eliminated from somatic progenitor cells. These elimination events effectively silence all genes on these chromosomes in all somatic cells., and Pprevious studies in lamprey and other eliminating species have provided strong evidence that other epigenetic silencing marks (DNA and histone posttranslational modifications) are enriched in the germline-restricted chromosomes and contribute to micronucleus packaging during elimination. These silencing marks include the histone marks H3K9me3 and H4K20me3, which are respectively deposited by KMT1A/SUV39 and KMT5/SUV420 methyltransferases in . To test whether lamprey homologs of methyltransferases contribute to deposition of these marks on elimination micronuclei and whether these marks contribute to the highly coordinated process of DNA elimination in sea lamprey, we leveraged CRISPR/Cas9 gene editing and lightsheet imaging to investigate their potential roles during early development and during the progression of DNA elimination. Analysis of knockout embryos for four methyltransferases show that these KMT genes contribute to the deposition of repressive histone marks on micronuclei, but are not essential for programmed DNA elimination per se. Analyses of later embryogenic stages suggests that these marks may contribute to interim silencing of germline-specific chromosomes, and reveals major impacts on post-blastula survival and developmental patterning.

overall_design: RNA-seq profiling of D2 and D3 wildtype embryos and their KMT1 and KMT5A knockout derivatives.

first: Kaan

middle: I

first: Claire

last: Scott

first: Cody

last: Saraceno

first: Vladimir

last: Timoshevskiy

first: Zachary

middle: D

last: Root

first: Jeramiah

middle: J

last: Smith


title: Developmental and transcriptional programs that define the initiation of the forelimb II

city: Austin

first: Vighnesh

last: Ghatpande

state: Texas

address: 2500 Speedway

department: Molecular Biosciences

institute: University of Texas at Austin

summary: The vertebrate forelimb initiates as a localized swelling in the somatic lateral plate mesoderm (somatic LPM) in response to Tbx5-dependent transcription. The molecular pathways driving limb morphogenesis have been extensively studied but the steps directly preceding limb bud formation remain poorly characterized. To address this, we defined the temporal onset of forelimb initiation in mouse embryos using sequencing based high-throughput approaches (RNA-seq, scRNA-seq, ChIP-seq, and Ribo-ITP) benchmarked to known features in forelimb development, identifying four distinct stages. Using scRNA-seq at the onset of forelimb-specific transcription, we determined the transcriptional profile of the somatic LPM and identified signature genes that distinguish the nascent forelimb from other cell types. This group includes multiple genes involved in neural projection as well as cell adhesion. Interestingly, these genes are highly enriched for TBX5 binding sites, suggesting they are candidate early transcriptional targets of  TBX5. As TBX5 is essential for forelimb outgrowth, the identification of these genes suggests new mechanistic models for TBX5-driven limb initiation.

overall_design: Two 15 somite-stage Fgf10+/+ and two 16 somite-stage Fgf10-/- embryos (E8.75) were dissected in cold 1X DPBS . The heart and tissues anterior to somite 7 and posterior to somite 13 were dissected away. The resulting core of embryonic tissue included the forelimb field as well as other embryonic tissues present at this axial level. Single embryos were trypsinized and then filtered through a cell strainer, transferred into a 1% BSA coated tube and centrifuged for 10 minutes at 500g at 4°C. Cells were fixed as described using (Tran et al., 2022) and ~58-73k cells per embryo were stored in -80℃. scRNASeq libraries were prepared using the Parse Evercode WT Mini v2 kit according to the manufacturers protocol. The libraries were sequenced on an Illumina NovaSeq X Plus.

first: Can

last: Cenik

first: Steven

last: Vokes

first: Alecxander

last: Lewis


title: Antibacterial activity of Questiomycin A against Mycobacterium tuberculosis by directly targeting FabD

city: Beijing

first: ling

middle: ling

last: xu

address: Beimachang No 97

department: Department of Pharmacology

institute: Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute

summary: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat, particularly due to the rise of multidrug-resistant TB (MDR-TB). Current treatment limitations highlight the urgent need for new therapeutics to improve efficacy and shorten therapy duration. Through high-throughput screening, we identified Questiomycin A (QM), a phenoxazinone compound with promising anti-tuberculosis activity against drug-sensitive and drug-resistant Mtb strains. Transcriptomic profiling indicated disruption of cell wall-associated pathways, while thermal proteome profiling (TPP) identified fabD (malonyl CoA-acyl carrier protein transacylase, MCAT), a key enzyme in mycolic acid biosynthesis, as a potential target. Surface plasmon resonance (SPR), enzymatic assays, and genetic manipulation confirmed QM directly binds to and inhibits fabD. QM disrupts cell wall integrity, increases permeability, and causes pH imbalance, proton motive force collapse, ultimately resulting in bactericidal effects. These findings reveal that QM targets fabD to compromise cell wall homeostasis in Mtb, providing a foundation for developing novel anti-tubercular agents targeting fabD.

overall_design: Mtb H37Rv treated with DMSO or QM (4 × MIC) for 6 h. Cells were harvested after treatment with RNA protect bacterial reagent (Qiagen, Germany), lysed in RLT buffer + β-mercaptoethanol, and disrupted with zirconia beads. Total RNA was extracted using RNeasy Mini Kit (Qiagen, Germany) and eluted with DEPC water.

first: Lingling

last: Xu

first: Manyi

first: Bin

last: Wang

first: Xinda

last: Li

first: Qiyue

last: Jia

first: Chennan

last: Liu


title: Oncogenic LncRNA SLC16A1-AS1 Cooperates with NSUN2 to Stabilize GRP78 mRNA via m5C Modification in Gastric Cancer [AGS]

first: wenjing

last: zhao

overall_design: RNA-seq analysis of AGS gastric cancer cells with SLC16A1-AS1 knockdown (siSLC16A1-AS1) compared to control cells (siNC). Two biological replicates per condition were sequenced. Sample s_NC_2 and s_1_2 were excluded from analysis due to being outliers.

first: Beiyao

last: Zheng

first: Wenjing

last: Zhao

first: Yan

last: Jin

first: Wentao

last: Sun

first: Yong

first: Qi

last: Zhang

first: Yue

first: Jin

first: Dong

last: Chen

first: Ke

last: Ren

first: Wei

first: Yuanyuan

first: Li

last: Yuan

first: XueJun

first: Fen

last: Yang

first: Jinfei


title: Vascular Basement Membrane Laminins Modulate  Functional Zonation of Cerebral Microvessels [scRNA-seq]

first: Lydia

last: Sorokin

summary: We investigated whether vascular basement membrane (BM) laminins influence vascular zonation by performing single-cell RNA sequencing (scRNAseq) on cerebral blood vessels from Lama4-/- mice - lacking the major vascular laminin 4 in endothelial and smooth muscle BMs - and wild-type littermates. Our dataset expands existing cerebral vascular transcriptomic profiles and reveals that Lama4-/- endothelial cells exhibit increased arterial marker expression and reduced postcapillary venule identity. In vitro and in vivo studies indicate that compensatory upregulation of laminin 5  in Lama4-/- vessels enhances expression of junctional proteins (Ocln, Cldn5) and promotes vessel contractility via increased expression of contractile genes in pericytes, which reside within the endothelial BM. Additionally, loss of Lama4 upregulates expression of large artery markers (Gja4, Dll4, Edn1,Tgfb2) and resulted in elevated autotaxin (Enpp2) levels, a key enzyme in lysophosphatidic acid production implicated in stroke. Accordingly, Lama4-/- mice exhibit worsened stroke outcomes, driven not by immune infiltration or junctional defects, but by increased vascular permeability likely mediated by autotaxin and/or activation of resident myeloid cells. Our data suggest that laminin 4/5 ratios in vascular BMs regulate functional zonation between arterioles, capillaries and postcapillary venules by modulating metabolic pathways in endothelial and mural cells, and indirectly influencing resident myeloid cells.

overall_design: 8 weeks old mice were transcardially perfused with ice-cold PBS. Brains from 3 Lama4-/- and  3 corresponding WT  mice were pooled/group.  Brains from 3 Tek-cre:Lama5-/- mice  and  3 corresponding WT  mice were pooled/group.

first: Deshpande

last: Tushar

first: Sorokin

last: Lydia


title: Dynamic and cell-type specific transcriptional reprogramming underlies the floral transition in the maize shoot apical meristem

city: Shenzhen

first: liang

last: dong

address: No. 66, Gongchang Road, Guangming District, Shenzhen

institute: Sun Yat-Sen University

summary: The floral transition in maize represents a pivotal developmental switch that determines flowering time, environmental adaptation, and yield-related traits. However, the molecular mechanisms governing shoot apical meristem reprogramming and cell identity changes during this process remain poorly understood. By integrating time-course bulk RNA-seq, single-cell transcriptomics, chromatin accessibility, and transcription factor binding profiles, we construct a spatiotemporal molecular framework of the maize shoot apical meristem floral transition. Our analyses reveal global transcriptional reprogramming accompanied by pronounced cell type-specific regulation dynamics. At a global level, our transcriptional-level inference suggests that pathways associated with chromatin remodeling, environmental response, and reproductive development are sequentially activated, based mainly on transcriptional-level inference. We further identify a ZmMADS69-ZmRap2.7-ZMM4 regulatory module that fine-tunes the floral transition within the shoot apical meristem. At single-cell resolution, we find that the floral transition is not driven by a uniform transcriptional switch, but instead emerges from the coordinated action of spatially distinct shoot apical meristem domains. Through differential expression, trajectory, and co-expression module analyses, we further identify previously unrecognized roles for the inflorescence regulators UNBRANCHED2 and UNBRANCHED3 in promoting the floral transition, suggesting that they coordinate floral induction with subsequent inflorescence development. Our study establishes a comprehensive spatiotemporal regulatory framework for maize floral transition, providing mechanistic insights into shoot apical meristem reprogramming and offering a foundation for identifying new regulators to improve maize adaptation and yield.

overall_design: We generated comprehensive time-course transcriptomic, single-cell transcriptomic, and chromatin accessibility atlases of maize SAMs during the floral transition, revealing a hierarchical and cell type–specific spatiotemporal division of labor in molecular signaling.

first: Liang

last: Dong

first: Yonghao

first: Fang


title: DhQS charged the shikimate pathway pathway in Thermus thermophilus HB27

city: Wuhan

first: Bu

last: xuying

address: Shizishan Street

institute: Huazhong agricultural university

summary: Temperature stress is a survival challenge that biological cells may encounter at any time. To sustain normal metabolic activities, organisms have gradually evolved strategies to respond promptly to temperature changes. The two-component system, typically involved in regulating the transcription of relevant genes in response to environmental stimuli, consists of a histidine kinase and a response regulator. This system mediates environmental signal transduction in microbial cells. This study identified DhqSR as a novel temperature-sensing two-component system in Thermus thermophilus HB27. It regulates the expression of type II 3-dehydroquinate dehydratase (DHQase) in the aromatic amino acid biosynthesis pathway, indirectly controlling aromatic amino acid synthesis and thereby altering cellular thermal adaptation capabilities.

overall_design: ChlP-seq for DhqSR system regulatored genes which work for temperature stress response. The samples were collected for 65°C cultured HB27 cells.

first: Xuying

last: Bu

first: Yingjun

last: Li


title: PHLDA1 is a shared diagnostic mediator for inflammatory fibrosis in heart and kidney

city: Suqian

first: Liangru

last: Shen

address: Qingyang road

institute: Kangshen Hospital

summary: Background: Inflammation-driven fibrosis represents a common pathological endpoint in both heart failure (HF) and chronic kidney disease (CKD), which together affect over 1 billion people worldwide. Understanding the shared molecular mechanisms by which inflammation contributes to the pathogenesis of HF and CKD is crucial for enabling early diagnosis and guiding the development of broad-spectrum therapeutic strategies. Methods: Utilizing multi-omics technologies and machine learning algorithms, we performed an integrative analysis of HF and chronic kidney disease CKD samples to uncover shared mechanisms underlying inflammation-induced fibrosis. Furthermore, key regulators identified through bioinformatic analysis were experimentally validated using primary cell co-culture assays, gene knockout approaches, and bulk RNA sequencing. Results: Single-nucleus RNA sequencing (snRNA-seq) revealed concurrent upregulation of IL-1β and Pleckstrin Homology-Like Domain Family A Member 1 (PHLDA1) in both cardiac M1 macrophages and injured proximal tubular epithelial (PTE) cells. PHLDA1 promotes IL-1β expression and knockout of PHLDA1 suppressed NF-κB signaling and renal fibrosis. Administration of IL-1β induced PHLDA1 expression in cardiac fibroblasts and renal PDGFRβ⁺ cells, suggesting a positive feedback loop that contributes to fibrosis. Conclusions: In this study, we identified PHLDA1 as a key driver of fibrosis in both the heart and kidney, acting through IL-1β mediated intercellular crosstalk. These findings highlight PHLDA1 as a promising therapeutic target for mitigating fibrosis in cardio-renal syndrome.

overall_design: We performed the PHLDA1 knock-out on CD10+ cells to investigate the inflammation level changes.

first: Xiaohang

last: Shao

first: Yongshou

last: Tao

first: Chentong

last: Wang


title: Maternal PM2.5 Exposure Impairs Inguinal White Adipose Tissue Plasticity in Middle-aged Male Mouse Offspring

city: Hangzhou

first: Renjie

last: Hu

address: 548 Binwen Rd

institute: Zhejiang chinese medical university

summary: In this study, we investigated the long-term adverse metabolic effects of maternal fine particulate matter (PM2.5) exposure on offspring, systematically characterized the pathogenic remodeling of inguinal white adipose tissue (iWAT) in middle-aged male offspring through scRNA-seq, and explored the underlying mechanisms of iWAT fibrosis under in vivo and in vitro conditions.

overall_design: Pregnant mice were randomly assigned to the filtered air (FA) group and the concentrated PM2.5 exposure group (PM2.5). The exposure protocol was 12 hours per day (from 08:00 to 20:00) for 19 successive days (gestational day (GD) 0-18) using a whole-body inhalation exposure system located on the campus of Zhejiang Chinese Medical University (ZCMU). At birth (postnatal day 0, PND 0), the pups were indiscriminately culled to 6-8 per litter. The remaining pups were reared with their dams in a clean air environment. At PND 21, all pups were weaned and caged according to sex. Then, all weaned offspring were fed a standard chow diet and weighed weekly. At PND 56 (adult) and PND 365 (12 months old, middle-aged), the offspring from each litter were euthanized and necropsied to collect serum and organs (i.e., iWAT, eWAT, and BAT) for further analysis. The fresh iWAT isolated from middle-aged male offspring was used to perform scRNA-seq.

first: Ran

first: Limin

first: Sanduo

first: Hanshu

last: Chu

first: Lu

last: Zhang

first: Li

last: Qin

first: Qinghua

last: Sun

first: Ying

last: Liu

first: Kezhong

first: Cuiqing


title: Palmitoylethanolamide (PEA) Regulates Cell Cycle Progression and Promotes an Anti-Inflammatory Transcriptomic Signature in C2C12 Skeletal Muscle Cells

city: Liverpool

first: Daniel

middle: John

last: Owens

address: Byrom Street

department: Research Institute for Sport and Exercise Science

country: United Kingdom

institute: Liverpool John Moores University

summary: Palmitoylethanolamide (PEA) is an endogenous lipid mediator with recognized immunomodulatory actions, yet its effects in skeletal muscle remain poorly defined. We investigated whether PEA influences myogenesis and profiled the acute transcriptomic response of differentiated C2C12 myotubes. Dose-tolerability assays identified reduced metabolic activity and viability at 100 µM PEA, so 10 µM was used for subsequent experiments. Across differentiation, PEA decreased myotube number (90.3 ± 10.6 vs 112.6 ± 10.1 in control) while increasing nuclear fusion index (37.8 ± 5.7% vs 30.7 ± 3.2%); myotube area was unchanged. In myoblasts, 24 h PEA exposure increased the proportion of cells in G0/G1 (48.2 ± 1.2% vs 42.3 ± 1.9%) with a concomitant reduction in S-phase (21.7 ± 1.2% vs 25.5 ± 1.2%), consistent with G1 arrest and reduced proliferative drive. RNA sequencing revealed a distinct transcriptional signature after 24 h PEA treatment, with 1,952 differentially expressed genes (1,028 upregulated; 924 downregulated, q < 0.05). Pathway-level changes encompassed cytokine–receptor interactions, chemokine, JAK–STAT, NF-κB, NOD-like and Toll-like receptor signalling. PEA downregulated NF-κB target/pro-inflammatory cytokine genes (Il1a, Il1b, Il12a, Il33, Tnfrsf19) while upregulating interferon-related and chemokine genes (e.g., Stat2, Oas1b, Gbp7, Cxcl14, Ccl5), indicating an anti-inflammatory/immune-priming profile. Notably, N-acylethanolamine acid amidase (Naaa), a lysosomal PEA hydrolase, was highly expressed and significantly induced, whereas fatty acid amide hydrolase (Faah) was low and unchanged, suggesting a muscle-specific bias toward NAAA-dependent PEA metabolism. Peroxisome proliferator-activated receptor-α (PPARα) was expressed at low levels and unaffected by PEA, indicating that the observed responses occur largely independent of canonical PPARα signalling. Together, these data show that PEA biases skeletal muscle toward a less proliferative but more fused and inflammation-resolving phenotype, accompanied by transcriptional reprogramming of immune pathways and preferential engagement of NAAA. While in vitro concentrations exceed reported plasma levels and mRNA changes may not fully predict protein/function, these findings provide the first comprehensive transcriptomic characterisation of PEA in myotubes and motivate in vivo studies to test whether PEA’s dual actions translate into benefits for muscle regeneration, adaptation, or anti-atrophy interventions.

overall_design: RNAseq profiling of C2C12 myotubes treated with palmitoylethanolamide or vehicle control

first: Mark

middle: R

last: Viggars

first: Paige

last: Cole

first: Scott

middle: H

last: Gillham

first: Graeme

last: Close


title: Multi-omics data analysis for the JGOG3025-TR1 ovarian clear cell carcinoma cohort.

city: Kyoto

first: Kohei

last: Hamada

address: 54 Shogoin Kawahara, Sakyo, Kyoto

department: Gynecology and Obstetrics

country: Japan

institute: Kyoto University Graduate School of Medicine

summary: The JGOG3025 study was conducted by the Japanese Gynecologic Oncology Group (JGOG) on 710 patients with epithelial ovarian cancer (NCT03159572). In the JGOG3025-TR1 study, fresh frozen tumor tissues from 189 cases diagnosed as clear cell carcinoma (CCC) in the central pathological review were submitted to total RNA-sequencing.

overall_design: Expression profiling of ovarian clear cell carcinoma


title: Extracellular Vesicle Cargo from Lipofibroblasts Mitigates COPD by Alveolar Type II Cell Restoration

city: Minato-ku

first: Yuta

last: Hirano

state: Tokyo

address: 3-25-8 Nishi-shimbashi

department: Internal Medicine

institute: The Jikei University School of Medicine

summary: Rationale: Emerging research highlights cellular abnormalities in Chronic Obstructive Pulmonary Disease (COPD), focusing on alveolar type 2 (AT2) cells, which are key to lung tissue repair and normal cellular differentiation. Lipofibroblasts (LipoFBs), stromal fibroblasts containing lipid droplets, are closely associated with AT2 cells and support their function. Objectives: We present a comprehensive investigation into the therapeutic potential of extracellular vesicles (EVs) derived from LipoFBs (LipoFB-EVs) in COPD treatment. Methods: LipoFBs were induced from lung fibroblasts using Metformin or Rosiglitazone in vitro, and their EVs were isolated via ultracentrifugation for analysis. Main Results: They effectively mitigate key COPD pathologies such as cellular senescence and inflammatory responses in lung epithelial cells. This is achieved by reducing reactive oxygen species (ROS) levels and modulating DNA damage response pathways. Moreover, LipoFB-EVs demonstrate anti-fibrotic properties by inhibiting TGF-β-induced myofibroblast differentiation, surpassing conventional anti-fibrotic drugs. They also aid in restoring impaired AT2 stem cells, which are crucial for lung homeostasis, by enhancing their viability, colony-forming ability, and proliferation. Furthermore, we identify the presence of L-type amino acid transporter 1 (LAT1) within LipoFB-EVs, which mediates amino acid uptake, particularly leucine transport, and contributes to the restoration of AT2 cell dysfunction. Importantly, the administration of LipoFB-EVs in murine models of COPD resulted in significant improvements in airway inflammation, remodeling, obstruction, cellular senescence, and alveolar emphysema induced by both short- and long-term CS exposure. Conclusions: Our findings highlight the therapeutic potential of LipoFB-EVs as a novel regenerative therapy for COPD, offering promising avenues for future clinical interventions

overall_design: RNA sequencing was performed to compare gene expression profiles in primary human lung fibroblasts with or without rosiglitazone treatment, and in AT2 organoids with or without LipoFB-EV treatment.

first: Shota

last: Fujimoto

first: Yu

last: Fujita


title: RNA-seq for the Kyoto clear cell carcinoma cohort.

summary: Fresh frozen tumor tissues from 38 cases diagnosed as clear cell carcinoma (CCC) were submitted to total RNA-sequencing.


title: Vascular Basement Membrane Laminins Modulate  Functional Zonation of Cerebral Microvessels

first: Lydia

last: Sorokin

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

overall_design: Refer to individual Series


title: Effect of IL-7 therapy on virus-specific CD8 T cell response during chronic viral infection [multiomic]

city: Atlanta

first: Donald

last: McGuire

state: GA

address: 1462 Clifton Road room 412

institute: Emory University School of Medicine

summary: PD-1+TCF-1+ stem-like CD8 T cells, also referred to as progenitors of exhausted T cells (TPEX), are a crucial resource pool for maintaining CD8 T cell during chronic viral infections and cancer. These stem-like CD8 T cells are a key therapeutic target in antiviral and anticancer immunotherapy as they provide a proliferative burst of effector CD8 T cells upon PD-1 blockade therapy. In our study we show that IL-7 therapy preferentially expands these stem-like CD8 T cells, using NT-I7, a long-acting hybrid Fc-fused recombinant human IL-7 (rhIL-7-hyFc, efineptakin alfa). Single-cell gene profile analysis revealed a proliferating cluster induced by NT-I7, distinct from previously described stem-like, transitory effector, or terminally exhausted subset cluster. This cluster exhibited an enriched stem-like signature, including transcription factors and costimulatory molecules associated with stem-like CD8 T cells. Notably, the cluster was enriched with genes related to lymphocyte migration. Consistent with this gene profile, there was a significant increase in stem-like CD8 T cells in circulation and peripheral tissues after NT-I7 treatment, contrasting with their resident property in lymphoid organs. Our data suggest the potential of NT-I7 therapy to enhance antiviral and anticancer immunotherapies by amplifying the stem-like CD8 T cell pool and mobilizing them to the peripheral target sites.

overall_design: C57Bl/6J mice were intravenously infected with 2x10^6 LCMV clone-13 with transient CD4 depletion. >45 days post infection, mice were treated with a single dose of injection buffer or NT-I7, a hybrid Fc-fused recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa). 8 or 14 days after the injection, LCMV-GP33 Tet+ CD8 T cells from the spleen were sorted for single cell RNA sequencing.

first: Judong

last: Lee

first: Chrstinia

last: Niavi

first: Eunseon

last: Ahn

first: Haydn

middle: T

last: Kissick

first: Rajesh

middle: M

last: Valanparambil

first: Tahseen

last: Nast

last: Hua

first: Rebecca

middle: C

last: Obeng

first: Alexandra

last: Wolfarth

first: Danielle

last: Borgonia

first: Sara

last: Ferrando-Martinez

first: Donghoon

last: Choi

first: Byung Ha

first: Rafi

last: Ahmed


title: Single-Cell RNA Sequencing Uncovers Neutrophil Clusters Associated with Autoimmune Neuroinflammation

city: Birmingham

first: Yong

last: Wang

state: AL

address: 1918 University Blvd

department: Cell, Developmental and Integrative Biology

institute: University of Alabama at Birmingham

summary: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) associated with multifocal inflammation and axonal degeneration, which is mediated by innate and adaptive immune cells. The Janus Kinase (JAK)/Signal Transducers and Activators of Transcription (STAT)/Suppressors of Cytokine Signaling (SOCS) pathway regulates the functionality of both innate and adaptive immune cells. We and others have documented dysregulation of the JAK/STAT/SOCS axis in T-cells and astrocytes in neuroinflammation, however, less is known about this axis in innate immune cells. Our previous studies using the Experimental Autoimmune Encephalomyelitis (EAE) model of MS demonstrated that mice lacking Socs3 in myeloid cells, both macrophages and neutrophils (Socs3ΔLysM), developed a severe, brain-targeted form of EAE (btEAE), with increased cerebellar infiltration of activated neutrophils. To examine the role of neutrophils specifically, we generated mice with Socs3 deletion exclusively in neutrophils (Socs3ΔLy6G). EAE was induced in Socs3ΔLy6G mice and Ly6G+/- control mice, and we observed that Socs3ΔLy6G mice exhibit clinical signs of btEAE identical to Socs3ΔLysM mice, with more severe cerebellar demyelination and higher cerebellar infiltration of activated neutrophils and CD4+ T-cells compared to Ly6G+/- controls. The Socs3ΔLy6G mice also exhibit clinical symptoms of classical EAE (cEAE), which is associated with spinal cord (SC) involvement. Cerebellar neutrophils from Socs3ΔLy6G mice exhibited a primed phenotype with increased CD11b expression, reduced CD62L expression, increased reactive oxygen species, and formation of neutrophil extracellular traps (NETs). Depletion of neutrophils ameliorated btEAE clinical disease, demonstrating the pathogenic properties of these cells. Single-cell RNA Sequencing (scRNA-Seq) was performed to determine the transcriptional profiles of neutrophils from cerebellum (CB) and SC associated with EAE. Five neutrophil clusters were identified in naïve mice and those with EAE, with an expansion of two clusters (Neu2 and Neu4) in Socs3ΔLy6G mice with EAE. Notably, high levels of Saa3, Il1b and Cxcl2 were detected in the Neu2, Neu3, Neu4 and Neu 5 clusters at the peak of EAE disease. Strikingly, Serum Amyloid A3 (Saa3) mRNA and protein expression was markedly enhanced in the CB and SC from Socs3ΔLy6G EAE mice compared to Ly6G+/- mice. Human SAA1 is the homologue of mouse Saa3. SAA1 expression was also substantially elevated in plasma from MS patients compared to healthy controls. Collectively, our study demonstrates neutrophil heterogeneity in both the CB and SC of Socs3ΔLy6G mice with EAE, transcriptional profiles associated with EAE disease, and potential mediators such as Saa3 that may serve as a therapeutic target to dampen autoimmune neuroinflammation.

overall_design: We carried out single cell RNAseq on live immune cells (CD45+CD11b+) from the cerebellum (CB) and  spinal cord (SC) of Socs3ΔLy6G mice with EAE (n=3), SC of Ly6G+/- mice with EAE (n=3),  combined SC of naive Ly6G+/- mice (n = 3), combinded SC (n = 4) and combined CB (n = 4) of naive Socs3ΔLy6G mice.

first: William

last: Turbitt

first: Hongwei

last: Qin

first: Etty

middle: N

last: Benveniste


title: Microglial Phagocytosis of Bipolar Cells Triggers Inner Retinal Degeneration in Rs1-KO Mice

city: Bucheon

first: Hun Soo

last: Chang

address: 170, Jomaru-ro

country: South Korea

institute: Soonchunhyang University

summary: X-linked retinoschisis (XLRS), caused by Retinoschisin 1 (RS1) gene mutations, leads to progressive retinal degeneration. While photoreceptor loss is a hallmark of the disease, its early pathogenic mechanisms are not well understood. Using CRISPR/Cas9-edited Rs1-exon2-knockout mice, we investigated the temporal progression of the retinal degeneration. Single-cell RNA sequencing revealed that the degeneration of bipolar cells, particularly the OFF-cone subtype, precedes photoreceptor loss. This early degeneration was driven by microglial activation and their subsequent phagocytosis of bipolar cells via phosphatidylserine exposure and C3b activation that was independent of apoptosis. These findings reveal a temporal sequence of neurodegeneration in XLRS, highlighting bipolar cells as a critical therapeutic target for early intervention.

overall_design: Rs1-exon2-knockout (Rs1-/y) mice were generated on a C57BL/6J background using CRISPR/Cas9 genome editing. Hemizygous Rs1-/y males were obtained by mating heterozygous (Rs1-/+)females with wild-type C57BL/6J males, and used for experiments at 8 and 24 weeks. Retina of the experimental animals were obtained and analysed using scRNA-seq.

first: Tae Kwann

last: Park


title: Ze-qi decoction inhibits neutrophil extracellular trap formation to suppress the progression and metastasis of non-small-cell lung cancer

city: Jinan, Shandong Province

first: Yiyang

last: Jiang

address: Shandong University of Traditional Chinese Medicine, Qianfoshan Campus

institute: Shandong university of traditional Chinese medic

summary: Non-small cell lung cancer (NSCLC) research has been exploring complementary and well-established methods with clear mechanisms and less toxicity. Immune dysregulation is vital in the growth and metastasis of NSCLC. Although Ze-qi decoction (ZQD) exhibits therapeutic efficacy in patients with NSCLC, the specific mechanisms remain unclear. UPLC-HRMS was used to identify the primary chemical components. The potent molecular mechanisms were analyzed using network pharmacology and transcriptomic technology. The underlying molecular mechanisms were further investigated in vivo experiments. UPLC-HRMS revealed that 297 bioactive compounds were absorbed into the blood. Combined with the pharmacological analysis, liquiritigenin, vibsanin B, and 11-keto-beta-boswellic acid were revealed as potential active ingredients. Pharmacological analysis and transcriptomic profile indicated neutrophil extracellular trap (NET) formation as the anti-NSCLC target of ZQD. In vivo, ZQD hindered neutrophil recruitment and activation by decreasing hypoxia-inducible factor-1α, CD18, and Intercellular adhesion molecule-1 levels and suppressed NET formation, as evidenced by the downregulated biomarkers. These results were confirmed in the lung metastasis model.

overall_design: RNA-seq of mouse substaneous tumor between control and high dose of ZQD treatment was applied at day 21 after ZQD treament.

first: Binbin

last: Li

first: Qian

last: Meng

first: Xiangyang

last: Liu

first: Minmin

last: Yu

first: Xue

first: Fei

last: Xu


title: Identification of CADM1 as an Immunotherapeutic Target and Evaluation of a Novel CADM1-Targeting Antibody-Drug Conjugate in Preclinical Osteosarcoma Models

city: Houston

first: Qi

state: TX

address: 7007 Bertner Ave

institute: UT MD Anderson Cancer Center

summary: Due to the paucity of validated cell surface osteosarcoma-specific targets, patients with this condition have long been excluded from the benefits of antibody-drug conjugate (ADC) therapy observed in several solid and hematologic malignancies. Our comprehensive surfaceome and RNA-seq profiling approach identified osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas but minimally expressed in normal tissues. As a result, one such antigen, CADM1, was selected for the generation of an ADC.

overall_design: To identify osteosarcoma-specific cell-surface antigens that are highly expressed in osteosarcomas, 17 osteosarcoma cell lines were used to perform RNA-seq, and gene expression profiling was analyzed using 150-bp paired-end RNA-seq, achieving an average coverage of 26.5 million reads per sample (range, 23.3–29.4 million reads).

first: Zhongting

last: Zhang

first: Yifei

first: Xiangjun

last: Tian

first: Jing

first: Gorlick

last: Richard


title: Vitamin B12 alleviates Verheij syndrome-like defects via phospholipid remodeling in a C. elegans PUF60 spliceosomopathy model

city: Cologne

first: Jonathan

last: Kölschbach

address: Joseph-Stelzmann-Straße 9B

department: Antebi

institute: Max Planck Institute for Biology of Ageing

summary: Verheij syndrome (VRJS) is a rare genetic disorder caused by mutations in the poly(U)-binding splicing factor 60 (PUF60), a core component of the spliceosomal complex. VRJS triggers multiple congenital anomalies, but the underlying pathomechanisms remain poorly understood. Mutation of the Caenorhabditis elegans PUF60 ortholog, rnp-6, recapitulates several hallmarks of VRJS, including growth delay and smaller body size. Here, we demonstrate that developmental defects in rnp-6 mutants are rescued by dietary K12-type E. coli strains. Through complementary genetic screens and multiomic analysis, we identify vitamin B12 as a potent suppressor of these defects, acting via the methionine/S-adenosylmethionine/phosphatidylcholine metabolic axis. Mechanistically, rnp-6 mutation causes aberrant splicing of metabolism-related genes and nhr-114, an HNF4 homolog and transcriptional master regulator of lipid and one-carbon metabolism, leading to impaired cellular methylation potential, dysregulated phospholipid metabolism, and activation of the integrated stress response (ISR). Vitamin B12 supplementation restores metabolic balance, suppresses ISR, and activates mTORC1 signaling to rescue growth and developmental phenotypes. Remarkably, restoration of nhr-114 splicing alone suffices to correct rnp-6 developmental defects. Our findings establish C. elegans as a tractable model of PUF60-deficiency, and suggest VB12 as a promising therapeutic strategy to mitigate VRJS-related anomalies.

overall_design: RNA-seq profiling of D1 adulthood C. elegans N2 (wildtype) and rnp-6(G281D) mutant strains, fed with E. coli OP50 or BW25113 diet, respectively. Four repeats per group.

first: Huang

last: Wenming

first: Kölschbach

last: Jonathan

first: Löhrke

last: Anna

first: Antebi

last: Adam


title: SypC, a Symbiont Outer-Membrane-Vesicle Protein, Impacts the Development and Persistence of the Squid-Vibrio Partnership

city: Pasadena

first: Vera

last: Beilinson

state: CA

address: 1200 E. California Blvd

department: Biology and Bioengineering

institute: Caltech

summary: Bacterial outer-membrane vesicles (OMVs) and the cargo they carry are increasingly recognized as a means of communication between microbial symbionts and the cells of their host. However, few studies have focused on the biochemical and molecular mechanisms underlying OMV-signaling during symbiosis onset and development. We show here that SypC, an OMV protein of the bioluminescent symbiont Vibrio fischeri, is taken up by cells of the squid host Euprymna scolopes where it assumes a new function, i.e., the facilitation of symbiont-induced light-organ morphogenesis. SypC is a Wza-like outer-membrane protein found in host-associated Vibrionaceae, and is essential for V. fischeri biofilm formation. Colonization or direct treatment with V. fischeri OMVs triggers host development, which is reduced or delayed if the host is instead exposed to a sypC mutant or its OMVs. RNA-seq analyses comparing light-organs colonized by the mutant versus its parent strain revealed  differential expression of host genes involved in immune responses and tissue morphogenesis. Immunocytochemical imaging revealed that, within the light-organ crypts, SypC-bearing OMVs are taken up by the host’s macrophage-like cells, revealing the mechanism by which SypC travels throughout the tissue to trigger morphogenesis. Taken together, the data show that, in addition to its role in biofilm formation, SypC has a second function promoting colonization and the induction of symbiotic-tissue development. These findings provide a critical piece of a puzzle whereby a rich array of host and symbiont molecules work in concert to orchestrate normal symbiont colonization and host development within the first hours to days of symbiosis.

overall_design: Hatchling squid where exposed for 24hr to either no bacteria (APO), wild-type (WT/SYM) bacteria, or muant bacteria (sypC). 4 replicates where used. Extract RNA was used with Nanostring to see gene expression across samples.

first: Jill

last: Kuwabara

first: Alexis

last: Hargadon

first: Grischa

last: Chen

first: Xiao-Meng

last: Hu

first: Mark

last: Ladinsky

first: Kathleen

last: Hackett

first: Joseph

last: Dillard

first: Karen

last: Visick

first: Edward

last: Ruby

first: Margaret

last: McFall-Ngai


title: Chemical Reprogramming of Human T Cells to Pluripotent Stem Cells

first: Ruoqi

last: Cheng

state: Beijing

address: NO.5, Yiheyuan Road, Haidian District

department: School of Life Sciences

institute: Peking University

summary: Chemical reprogramming provides an innovative approach to convert somatic cells into pluripotent state using small molecules, holding great promise for regenerative medicine. Since the successful generation of human chemically induced pluripotent stem (hCiPS) cells in 2022, this strategy has emerged as a powerful tool for inducing pluripotency in diverse cell types. However, whether terminally differentiated somatic cells with stable identities, such as T cells, could be chemically reprogrammed toward pluripotency, remains unknown. Here, we adapted a chemical reprogramming method to successfully reprogram CD3+ and CD8+ T lymphocytes into hCiPS (hT-CiPS) cells. These cells fulfilled characteristics of human pluripotent stem cells, and TCR rearrangements analysis confirmed their T cell origin. Moreover, hT-CiPS cells can efficiently generate TCR-expressing cells and re-differentiate to CD4/CD8 positive T cells. Our findings reveal that chemical reprogramming can effectively convert terminally differentiated cells into pluripotent cells, holding promise for clinical applications in immunotherapy and regenerative medicine.

overall_design: A total of 22 bulk RNA-seq data were analyzed, including those from CD3T, CD8T, hCiPSC, and S1 cells. Each condition has 2 biological replicates.

first: Yanglu

last: Wang

first: Fangqi

last: Peng

first: Lin

first: Jingyang

last: Guan

first: Hongkui

last: Deng


title: RNA-seq of OPM2 multiple myeloma cells treated with HDAC inhibitors panobinostat, romidepsin, and ricolinostat.

city: Yokohama

first: Yuki

last: Yamaguchi

state: Kanagawa

address: 4259, Nagatsutacho, Midori-ku

department: School of Life Science and Technology

institute: Institute of Science Tokyo

summary: Histone deacetylase (HDAC) inhibitors have been reported to exert synergistic antitumor effects with immunomodulatory drugs (IMiDs) in multiple myeloma,  although the underlying molecular mechanisms are not fully elucidated. To delineate pathways potentially involved in this synergy, we profiled gene expression changes induced by HDAC inhibition in the OPM2 multiple myeloma cell line. Cells were treated with panobinostat (10 nM), romidepsin (10 nM), or ricolinostat (100 nM) for 2, 5, or 20 hours, followed by RNA-seq analysis. Two independent biological replicates were generated for each condition. These data provide a resource for identifying HDAC inhibitor–responsive genes and pathways that may contribute to the cooperative activity of HDAC inhibitors and IMiDs in multiple myeloma.

overall_design: We analyzed the transcriptomes of OPM2 multiple myeloma cells treated with three histone deacetylase (HDAC) inhibitors: panobinostat (10 nM), romidepsin (10 nM), and ricolinostat (100 nM). Cells were harvested after 2, 5, and 20 hours of treatment. A vehicle control (DMSO) was included. For each condition, two independent biological replicates (n = 2) were generated.

first: Junichi

last: Yamamoto

first: Tomoko

last: Asatsuma-Okumura


title: To identify genes for radioresistance in lung cancer [CRISPR Screen]

city: Nanchang

first: Yi

last: Sang

state: Jiangxi

address: No.128,Xiangshan North Road

institute: Nanchang University

summary: To identify genes for radioresistance in lung cancer, unbiased CRISPR/Cas9 library knockout screening was performed in lung cancer containing a pooled 903 post-translational modification (PTM) related regulatory proteins library. Two populations of cells were either nonirradiated or irradiated at 9 Gy, and they were cultured in vitro. Then genomic DNA was acquired to readout the sgRNA representation by deep sequencing.

overall_design: CRISPR/Cas9 library knockout screening was performed in lung cancer containing a pooled 903 post-translational modification related regulatory proteins library.

first: Chun


title: Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment [ChIP-seq]

city: Mexico City

first: Víctor

middle: Julián

last: Valdés

state: Mexico City

address: Circuito Exterior s/n, Ciudad Universitaria

department: Departamento de Biología Celular y Desarrollo

country: Mexico

institute: Instituto de Fisiología Celular (IFC), Universidad Nacional Autónoma de México (UNAM)

summary: Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications preserving the epigenetic memory of each cell lineage. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Poly-comb recruitment remain unclear. To address this, we engineered an auxin-inducible degradation system to reversibly deplete and reintroduce the endogenous PRC2 core subunit Suz12 in mouse embryonic stem cells (mESCs). Genome-wide profiling at early recovery time point revealed PRC2 nucleation sites, characterized by rapid Suz12 and H3K27me3 re-accumulation and signal strength.

overall_design: ChIP-seq of Suz12 (GFP antibody) and H3K27me3 in mouse embryonic stem cells (mESCs) with an Auxin Inducible Degradation (AID) system of the Suz12 core subunit of PRC2. Experimental conditions include Control, Auxin and Reintroduction samples. For each condition, two biological replicates were conducted.

first: Itzel

last: Hernández-Romero

first: Carlos

last: Peralta-Alvarez

first: Victor

last: Valdes


title: The intestinal crypt is a potential reservoir for hepatitis E virus infections

city: Heidelberg

first: Carl

last: Herrmann

address: Im Neuenheimer Feld 364

department: Institute of Pharmacy and Molecular Biotechnology

institute: Heidelberg University

summary: The hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Although most HEV infections are self-limiting, zoonotic genotypes can establish persistent infections in immunocompromised individuals. Transmitted via the fecal-oral route, HEV has been suggested to directly infect the intestinal epithelium, an organ composed of diverse cell types with high regenerative capacity. In this study, we demonstrate that HEV predominantly infects proliferative transit-amplifying and intestinal stem cells located within the crypts of human pluripotent stem cell-derived intestinal organoids (hIOs). Supporting this, we detected HEV RNA in the crypts of intestinal tissue from an HEV-infected patient. We further found that HEV can spread through cell division and establish persistent infection in hIOs for over 40 days, contrasting with acute hepatitis A virus, whose infections are rapidly cleared from hIOs. Given the self-renewal ability and metabolic constraints of proliferative intestinal progenitor cells, our findings suggest that intestinal crypts could serve as reservoirs for chronic HEV infection and highlight the crypt as a new primary target for viral infection in the gastrointestinal tract.

overall_design: iPSC-derived small intestinal organoids infected with cell culture derived HEV and harvested at D14 post infection. Organoids were singularized and the single cell supsensions were directly used for 10X genomics scRNA sequencing.

first: Sarah

last: Prallet

first: Niclas

last: Maier

first: Albert

last: Li

first: Cassian

last: Afting

first: Hao-En

last: Huang

first: Jungen

last: Hu

first: Elif

last: Toprak

first: Deb

last: Keya

first: Ombretta

last: Colasanti

first: Nancy

last: Janampa

first: Julien

last: Marlet

first: Claudia

last: Beisel

first: Carolin

last: Mogler

first: Philip

last: Puchas

first: Patrick

last: Behrendt

first: Tobias

last: Boettler

first: Eike

last: Steinmann

first: Senjuti

last: Saha

first: Vibor

last: Laketa

first: Volker

last: Lohmann

first: Joachim

last: Wittbrodt

last: Hermann

first: Michael

last: Dill

first: Viet Loan

last: Dao Thi


title: Liver RNA-seq from obese mice following Roux-en-Y gastric bypass or sham surgery under chow or high-fat diet conditions

city: Mineola

first: Louis

last: Ragolia

state: New York

address: 101 Mineola Blvd, Suite 4-004

department: Foundations of Medicine

institute: NYU Grossman Long Island School of Medicine

summary: This study investigates how Roux-en-Y gastric bypass (RYGB) and high-fat diet (HFD) influence liver gene expression in mice. RNA sequencing was performed on liver samples from diet-induced obese male C57BL/6 mice that underwent either RYGB or sham surgery, followed by an 8-week post-operative period on either chow or HFD. Raw sequencing reads (FASTQ) and gene-level count data are provided to support investigation of RYGB- and diet-associated transcriptional changes in hepatic tissue.

overall_design: Male C57BL/6 mice were fed a high-fat diet for 12 weeks to induce obesity, then underwent either Roux-en-Y gastric bypass (RYGB) or Sham surgery. Post-operatively, mice were maintained on either chow or high-fat diet for 8 weeks. The study included four groups: Sham Chow, RYGB Chow, Sham HFD, and RYGB HFD, with biological replicates in each group.

first: Matthew

last: Stevenson

first: Munichandra

last: Tirumalasetty

first: Ankita

last: Srivastava

first: Qing

last: Miao

first: Collin

last: Brathwaite


title: Control of telomerase recruitment and end protection by independent shelterin components

city: Bethesda

first: Eros

last: Lazzerini Denchi

address: 9000 Rockville Pike

institute: NCI

summary: Telomeres are proposed to alternate between “closed” states, in which chromosome ends are protected from DNA damage signaling and inaccessible to telomerase, and “open” states, where they become accessible for telomerase mediated elongation but less protected. Whether these states reflect distinct molecular mechanisms or mutually exclusive structural conformations remains unclear. Here, we develop a single-cell assay to monitor telomerase activity in mouse embryonic stem cells. Using this approach, we demonstrate that the shelterin component TPP1 is essential for telomerase recruitment via its interaction with TIN2, independently of POT1. In contrast, POT1 is dispensable for telomerase function but required for telomere end protection, acting independently of TPP1. These findings challenge the classical open-closed telomere model and reveal that telomerase recruitment and end protection are mediated by genetically and molecularly separable mechanisms.

overall_design: We sequenced genomic DNA enriched for sequences that are not cut by frequence cutters to detect incorpration of mutant repeats at telomeres

first: Ranjodh

last: Sandhu

first: Gianna

last: Tricola

first: Si Young

last: Lee


title: Human Kidney Tubuloids Model of Repeated Cisplatin-induced Cellular Senescence and Fibrosis for Drug Screening

city: Bunkyo

first: Yuki

last: Nakao

address: Yushima 1-5-45

summary: In the pursuit of pathophysiological models for assessing renal drug response, the development of kidney organoids derived from human pluripotent stem cells represents a significant step forward. However, recapitulating aging/senescence-associated pathophysiology remains challenging. Here, we present an innovative approach to generate epithelial-like structures known as “tubuloid” using primary human renal proximal tubular epithelial cells (hRPTECs) cultured from human resected kidneys, as a refined alternative. We evaluated the efficacy of tubuloids using cisplatin treatment. Tubuloids showed highly differentiated structures. Exposure to cisplatin increased γH2AX, Kidney Injury Molecule-1 (KIM-1) and Cleaved Caspase-3, markers for DNA damage response, epithelial damage and apoptosis respectively. Repeated cisplatin administration resulted in upregulation of the senescence markers. Additionally, increased secretion of inflammatory cytokines, indicating the induction of a senescence-associated secretory phenotype (SASP) were induced Supernatant collected from cisplatin-treated tubuloids induced myofibroblast activation, indicating the onset of renal fibrosis. We successfully established a tubuloid-based model of cisplatin-induced kidney injury using hRPTECs. Tubuloids can replicate cellular senescence, SASP, and fibrosis, which can recapitulate the phenotypes of chronic kidney disease (CKD). Furthermore, tubuloids provide a novel platform for studying the response of renal epithelial cells to toxins and therapeutics and offer innovative strategy for drug screening in a human-based fashion. In this study, we also performed bulk RNA sequencing on the tubuloids generated using established protocol to verify their cellular composition.

overall_design: Human renal proximal tubular epithelial cells derived from resected kidneys were seeded onto ultra-low-attachment plates, and Matrigel was added two days later. The cells were then expanded for two weeks in culture medium containing various growth factors to generate tubuloids. RNA was extracted from these tubuloids and subjected to bulk RNA sequencing.

first: Makiko

last: Mori

first: Yuta

last: Sekiguchi

first: Iori

last: Morita

first: Ryota

last: Shindoh

first: Shintaro

last: Mandai

first: Tamami

last: Fujiki

first: Hiroaki

last: Kikuchi

first: Fumiaki

last: Ando

first: Koichiro

last: Susa

first: Takayasu

first: Yuma

last: Waseda

first: Soichiro

last: Yoshida

first: Yasuhisa

last: Fujii

first: Kensuke

last: Miyake

first: Ayumi

last: Suzuki

first: Yuji

last: Nashimoto

first: Hirokazu

last: Kaji

first: Eisei

last: Sohara

first: Shinichi

last: Uchida

first: Yutaro


title: IFNγ-independent control of Mycobacterium tuberculosis infection in rhesus macaques

first: Sivaranjani

last: Namasivayam

address: 33 North Drive

department: NIAID

institute: NIH

summary: Control of Mycobacterium tuberculosis (Mtb) infection requires IFNγ in mice. In humans, IFNγ is critical for resistance to non-tuberculous mycobacteria (NTM), but its role in classic pulmonary tuberculosis is less clear. Here we block IFNγR1 signaling in rhesus macaques at different times post-infection. Short-term IFNγ blockade after tuberculoma formation rapidly reduced 18FDG-PET/CT scores of lung inflammation and changed macrophage gene expression. It also increased IFNβ, pDCs, plasma cells, killers and IFN-driven gene expression in neutrophils. Blockade started on the day of infection altered T and B cell responses and reduced cytokine levels in granulomas. Surprisingly, IFNγ blockade did not affect bacterial loads. We also find that patients with anti-IFNγ neutralizing autoantibodies develop extrapulmonary NTM disease, not pulmonary tuberculosis, despite immunological evidence of Mtb exposure. Thus, IFNγ has broad immunomodulatory effects during tuberculosis, especially on antiviral-like responses, but control of pulmonary Mtb infection does not require generating high levels of IFNγ.

overall_design: Male rhesus macaques, 3 years old, infecetd with ~40 CFU of Mycobacterium tuberculosis H37Rv. 45 days following ijfection, animals were treated with IFNgR blockade antibody or isotopye for 4 days. Granulomas were then isolated from each monkey and processed for scRNAseq using the 10X Genomics protocol

first: Shunsuke

last: Sakai

first: Keith

last: Kauffman

first: Eduardo

last: Fukutani

first: Artur

last: Queiroz

first: Christine

middle: E

last: Nelson

first: Erin

middle: F

last: McCaffrey

first: Ploenchan

last: Chetchotisakd

first: Jay

last: Buchanan

first: Alan

last: Sher

first: Carl

last: Feng

first: Joel

last: Ernst

first: Steven

last: Holland

first: Katrin

last: Mayer-Barber

first: Bruno

middle: B

last: Andrade

first: Christa

middle: S

last: Zerbe

first: Laura

last: Via

first: Daniel

last: Barber


title: HDACs repress runaway stress and cell identity to promote  reprogramming in root regeneration

city: Gif-sur-Yvette

last: Guillotin

address: Bâtiment 630, Avenue des Sciences

country: France

institute: Institute of Plant Sciences of Paris-Saclay - IPS2

summary: The widespread regenerative capacity of plants is due, in large part, to the ability of specialized cells to reverse their developmental course and reprogram to new cell identities. The path to reprogramming in plants has been termed dedifferentiation or transdifferentiation, but the sequential cellular states of regenerating plant cells remain an open question. To dissect the cellular progression of regenerating plant cells, we use a root regeneration system in the Arabidopsis root that does not require exogenous treatment, allowing us to follow endogenous reprogramming via single cell RNA/ATAC-seq, imaging, and mutant analysis. The earliest events were dependent on repressive chromatin modification, where Multiome analysis showed that Class I histone deacetylases (HDACs) HDA9 and HDA19 were needed to shut down old identities and to prevent a runaway stress response. Cell division mediates a second step needed for the acquisition of many new identity markers, where division rates were tuned by DOF transcription factor OBP1 accelerating and SMR5, 7, and 10 decelerating division rates in later hours. The results show how plants actively mediate the collapse of old identities within hours of injury and then tune cell division rates to rapidly reprogram cells to new identities.

overall_design: Arabidopsis root tips were cut at 130um from the tip to induce regeneration. The roots were then collected, uncut (CTR), or at 4h, 9h, 14h, 24h and 36h post cut. Certain replicates involve treatment with TSA, roscovitin and curcumin. Roots were protoplasted and scRNAseq was performed using 10xgenomics 3'UTR kit as per protocol. Data was then processed using CellRanger and Seurat. Additionaly, one dataset was obtained from Arabidopsis root nuclei treated or not with TSA 0 or 2h post cut. Multiome analysis was performed using 10x genomics Chromium Next GEM Single Cell Multiome ATAC + Gene Expression kit. Data was then processed using CellRanger and Signac.

first: Ramin

last: Rahni

last: Lee

first: Indie

last: Suresh

first: Brandon

last: Gorodokin

first: Graeme

last: Vissers

first: Kenneth

last: Birnbaum


title: RNA-seq data from GBM patients and paired organoids

city: Pozuelo de Alarcon

first: Angel

middle: Ayuso

last: Sacido

state: Madrid

address: Ctra. Pozuelo-Majadahonda KM 1.800.

department: Faculty of Experimental Sciences

country: Spain

institute: Universidad Francisco de Vitoria

summary: In this study, we have investigated the possibility of using patient derived organoids from GBM patients in order to select personalised treatments. As part of this study, we have performed RNA-seq on 11 paired tumors and their derived organoids without any treatment.

overall_design: This study contain 11 paired samples from GBM patients and their respctive derived organoids after 2 weeks in culture, all untreted. We wanted to investigate the similarities between the original tissue and the paired organoids

last: Ayuso Sacido

first: Noemi

last: Garcia Romero

first: Alvaro

last: Monago Sanchez


title: Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment [RNA-seq]

first: Víctor

last: Valdés

overall_design: RNA-seq of Suz12 in mouse embryonic stem cells (mESCs) with an Auxin Inducible Degradation (AID) system of the Suz12 core subunit of PRC2. Experimental conditions include Control, Auxin and Reintroduction samples. For each condition, three biological replicates were conducted.

first: Itzel

middle: A

last: Hernández-Romero

first: Carlos

last: Peralta-Alvarez

first: Victor

last: Valdes


city: Salvador

first: Artur

middle: Trancoso Lopo

last: Queiroz

address: Rua Waldemar Falcão, 121

country: Brazil

institute: Instituto Gonçalo Moniz

overall_design: male rhesus macaques, 3 years old, infecetd with ~40 CFU of Mycobacterium tuberculosis H37Rv

first: Shunsuke

last: Sakai

first: Sivaranjani

last: Namasivayam

first: Keith

middle: D

last: Kauffman

first: Eduardo

last: Fukutani

first: Christine

last: Nelson

first: Erin

last: McCaffrey

first: Ploenchan

last: Chetchotisakd

first: Jay

last: Buchanan

first: Alan

last: Sher

first: Carl

middle: G

last: Feng

first: Joel

last: Ernst

first: Steven

last: Holland

first: Katrin

last: Mayer-Barber

last: Andrade

last: Zerbe

last: Via

middle: L


title: Characterization of tumor cell lines derived from genetically engineered mouse models of bladder cancer

city: Madrid

first: Cristian

last: Suarez Cabrera

address: Av. Complutense 40

institute: CIEMAT

summary: We have generated various genetically engineered mouse models (GEMMs) of advanced bladder cancer that recapitulate various morphological variants of human tumors, with distinct histological characteristics, differing onset times or growth rates, and varying incidences of dissemination. To investigate the molecular pathways underlying these features, we performed a transcriptomic analysis of these models in comparison with control urothelium. Given that concurrent TP53 and RB1 alterations are frequently observed in human tumors and are associated with specific molecular subtypes and increased aggressiveness, this study aimed to develop and characterize new models comparing the combined loss of Pten, Trp53, and Rb1 (in an Rbl1-null background, due to functional compensation of Rb1 loss in mouse tissues) with the loss of Pten and Trp53 alone, where the retinoblastoma (Rb) family remains intact. In both models, basal urothelial cells were targeted using adenoviruses expressing Cre unther de control of the Krt5 promoter (Ad5-Krt5-Cre), while luminal urothelial cells were targeted using the murine Krt20 promoter (Ad5-Krt20-Cre). Despite the advantages offered by these GEMMs, their limitations—including unpredictable tumor onset, long latency periods, and difficulties in early tumor detection—led us to develop immunocompetent heterotopic models using tumor cell lines derived from primary tumors arising in GEMMs. These models enable more accurate tumor monitoring and synchronized growth, thereby improving the robustness of preclinical studies. Here, we provide a transcriptomic analysis of some of these bladder tumor-derived cells.

overall_design: Gene expression was compared among bladder tumor-derived cells generated from injection of Cre-expressing adevoviruses into the bladder of conditional Quadruple Knock-Out (QKO; Ptenflox/flox, Trp53flox/flox, Rb1flox/flox, Rbl1-/-) and Double Knock-Out (DKO; Ptenflox/flox, Trp53flox/flox) mice. This transcriptomic study included 1 DKO-Krt5 tumor-derived cell line (4K5), 1 DKO-Krt20 tumor-derived cell line (3K20), 2 QKO-Krt5 tumor-derived cell lines (CK5.A and K5.6), and 1 QKO-Krt20 tumor-derived cell line (CK20.D). Each cell line was analyzed in duplicate.

first: Ester

last: Munera-Maravilla

first: Mercedes

last: Pérez-Escavy

first: Carolina

last: Rubio

first: Cristina

last: Segovia

first: Iris

last: Lodewijk

first: Sandra

middle: P

last: Nunes

first: Álvaro

last: Martín de Bernardo

first: Ignacio

last: Reina

first: Esther

last: Montesinos

first: Lucía

last: Morales

last: Martínez

first: Mónica

last: Martínez-Fernández

first: Marta

last: Dueñas

first: Jesús

last: Paramio

last: Suárez-Cabrera


title: NTN1 cell-autonomously promotes fibrotic response in HSCs.

city: Shanghai

first: Jiahui

last: Zhao

address: Dongan road 130

institute: Fudan university

summary: Liver fibrosis is a hallmark of progressive liver diseases including metabolic dysfunction-associated steatohepatitis (MASH). Activated hepatic stellate cells (HSCs) are responsible for the excessive synthesis of extracellular matrix(ECM) proteins and collagen deposition in the liver, leading to progressive loss of hepatic functions. However, the nature of paracrine and autocrine signals driving HSC activation and fibrotic response within the liver microenvironment remains incompletely delineated. Here we uncover Netrin-1 (NTN1) as a crucial HSC-derived autocrine factor that promotes HSC activation and liver fibrosis. Hepatic NTN1 mRNA and protein levels were elevated during fibrosis associated with MASH and CCl4-induced liver injury. Hepatic NTN1 overexpression exacerbated diet-induced MASH pathologies and CCl4-induced liver fibrosis. Conversely, HSC-specific conditional ablation of NTN1 alleviated the progression of liver fibrosis. Mechanistic studies using cultured HSCs demonstrated that NTN1 promoted HSC activation in a cell-autonomous manner via a UNC5B and Ca2+-dependent signaling pathway. These findings illustrate the causative role of NTN1-mediated autocrine signaling in driving HSC activation and fibrotic response during liver disease, suggesting potential therapeutic targets for anti-fibrosis therapy.

overall_design: To critically assess the role of Netrin-1 in mediating HSC activation and liver fibrosis, we generated mice with HSC-specific ablation of Ntn1 using Lrat-Cre, an established genetic tool for conditional gene inactivation in HSCs, and subjected them to Gan diet feeding for 5 months. We also generated a recombinant adenovirus-associated virus (AAV) vector under the control of thyroxine binding globulin (TBG) promoter that directs liver-specific overexpression of Netrin-1. We transduced mice with control AAV-TBG-Vector or AAV-TBG-Ntn1 and subjected them to Gan diet feeding for 5 months.

first: Yajie

last: Peng

first: Hongyan

last: Lei

first: Tianyi

last: Wang

first: Huajuan

first: Xuelian

last: Xiong


title: Transcriptome analysis of the effect of RAD52 knockout on olaparib response in BRCA2-deficient, olaparib-resistant murine ovarian cancer cells (ID8-OR)

city: St. Louis

first: Dineo

last: Khabele

state: Missouri

address: 425 S. Euclid Avenue, CB 8064

department: Obstetrics and Gynecology

institute: Washington University in St. Louis

summary: This study investigates the role of RAD52 in PARP inhibitor-resistant BRCA2-deficient ovarian cancer, with a particular focus on identifying compensatory DNA repair pathways. To explore RAD52-regulated transcriptional programs, we used CRISPR/Cas9 to generate RAD52 knockout clones in the PARP inhibitor-resistant, BRCA2-deficient mouse ovarian cancer cell line ID8-OR. Scrambled guide RNA-transduced cells served as controls. Both RAD52 knockout and control cells were treated with either olaparib or vehicle. RNA was extracted from all samples (n=3 per group; four groups total) for transcriptome analysis. This dataset provides a valuable resource for investigating RAD52-dependent gene expression and alternative DNA repair mechanisms in the setting of PARP inhibitor resistance.

overall_design: Gene expression profiling of RAD52 knockout and control ID8-OR cells. Cells were treated with 1 μM olaparib or vehicle for 24 hours and collected in biological triplicate.

first: Yukihide

last: Ota


title: Highly efficient generation of functional TCRγδ+ T cells from human embryonic stem cells

city: 深圳市

first: 张

last: 雪燕

state: 广东省深圳市南山区

address: 南山区

institute: 华南理工大学

summary: This dataset presents comprehensive RNA sequencing (RNA-seq) data documenting the dynamic transcriptional landscape during the in vitro differentiation of human embryonic stem cells (hESCs) into functional TCRγδ+ T cells. The study captures stage-specific gene expression patterns across key developmental transitions, including: (1) pluripotent stem cell stage, (2) hematopoietic progenitor specification, (3) T-lineage commitment, and (4) mature TCRγδ+ T cell maturation. The data reveal critical transcription factors governing γδ T cell development (e.g., EGR3, SOX13) and genes  related to the proliferation and activation of T cells (e.g.,CD80, CD86, IL7R and IL15RA).            Pathway analysis highlights dynamic regulation of WNT signaling,TGF-beta, PI3K-AKT, and cytokine-mediated pathways (IL-17) throughout the differentiation cascade.

overall_design: RNA-seq profiling  was performed to reveal the expression profiles of cells at day10,15, 20 and 25 during hESCs to γδT cells differentiation.

first: Xueyan

last: Zhang

first: Chuxin

last: Chen

first: Yuyou

last: Duan


title: Differential Transcriptomic Modulation by Histone Deacetylase Inhibitor SAHA in LUAD and LUSC

city: guangzhou

first: Fei

address: jinsuilu 9

institute: Guangzhou Medical University

summary: Background: Histone deacetylases (HDACs) drive non-small-cell lung cancer (NSCLC) progression, yet HDAC inhibitor (HDACi) responses vary by tumor subtype. We compared the pan-HDAC inhibitor SAHA (vorinostat) in two NSCLC models-HER2-mutant lung adenocarcinoma (NCI-H1299; TP53del, NRASQ61K) and EGFR/PI3K-driven squamous carcinoma (NCI-H1703; PDGFRAamp, PIK3CAE542K)-to uncover lineage-specific mechanisms. Methods: Cells were treated with SAHA (10 µM, 24 h), a clinically relevant dose yielding ~1 µM free drug in plasma. Strand-specific RNA-seq was aligned to GRCh38.p13 and analyzed with edgeR and DESeq2 (FDR < 0.05, |Log₂FC|≥ 1). Pathway, protein-interaction, apoptosis (Annexin V/PI), and migration (scratch, trans-well + mitomycin C) assays complemented transcriptomics. Clinical relevance was assessed by correlating SAHA-regulated genes with disease-free survival in TCGA-LUAD and TCGA-LUSC via GEPIA2. Results: SAHA altered 1098 genes in H1299 and 1532 in H1703, with only 437 shared. In H1299, SAHA induced EMT and MAPK-feedback genes while repressing interferon/apoptosis pathways. In H1703, SAHA activated complement/ECM remodeling and suppressed cell-cycle regulators. Class II HDACs (HDAC4/6) were downregulated only in H1703. Functionally, H1703 exhibited greater apoptosis; H1299 showed stronger migration inhibition. SAHA-reversed gene signatures (e.g., HMMR, PLK1 in LUAD; PAPPA, SAMD11 in LUSC) were significantly associated with poor disease-free survival, defining HDAC9-HMMR/PLK1 and HDAC4/6-PAPPA/SAMD11 axes. Conclusions: SAHA elicits distinct subtype-specific transcriptional and phenotypic effects in NSCLC. These findings highlight the importance of genetic context in HDACi therapy and support tailored combinations-such as SAHA with MAPK inhibitors in LUAD or HDAC4/6-targeted approaches in LUSC-and the use of SAHA-modulated biomarkers for patient stratification.

overall_design: Total RNA was extracted from cells grown in 6-well plates (2 × 105 cells per well, ~70 % confluence at harvest) using TRIzol reagent (Invitrogen) and purified with the RNeasy Mini Kit (Qiagen), including an on-column DNase I digestion. RNA purity (A260/280 ratio = 2.05 ± 0.04, A260/230 ratio = 1.98 ± 0.03) was measured using NanoDrop 2000, and RNA integrity (RIN ≥ 9.6) was confirmed by an Agilent 2100 Bioanalyzer. High-quality RNA (500 ng per sample) was used to generate strand-specific poly(A) libraries with the NEBNext Ultra II Directional RNA Library Prep Kit. Libraries were pooled and sequenced on an Illumina NovaSeq 6000 platform (paired-end, 2×151 bp, median depth of 55 million reads per sample, Q30 >93% , ~130× transcriptome breadth).

first: Xiaohua

last: Deng

first: Lei

last: Shu

first: Huiyu

last: Cen

first: Yating

last: Huang

first: Xiaojun

last: Ma

first: Yinshan

last: Lin

first: Xiaoling

last: Guan

first: Chen

first: Xihua

last: Fu

first: Guoxing

last: You

first: Xi-Yong

last: Yu

first: Lingmin

first: Jianfen

last: Su


title: Genetic susceptibility to PM2.5 exposure drives transcriptional responses in pediatric asthma: insights from single-cell transcriptomics

city: Philadelphia

first: Jelte

last: Kelchtermans

state: PA

address: 3401 Civic Center Blvd

institute: Children's Hospital of Philadelphia

summary: Background. Exposure to fine particulate matter (PM2.5) increases asthma severity and reduces glucocorticoid responsiveness in children, yet the molecular mechanisms underlying PM2.5 sensitivity remain unclear. We previously identified a PM2.5-sensitive asthma phenotype and developed a PM2.5 sensitivity polygenic risk score (sPRS) correlated with asthma exacerbations and lung function decline. This study expands on these results using genetic mapping and single-cell transcriptomics to elucidate the biological pathways mediating PM2.5 sensitivity and generate hypotheses regarding potential therapeutic targets. Research Question. We aimed to determine whether genetic variants associated with PM2.5 sensitivity converge on specific pathways or transcriptional regulators and assess their role in glucocorticoid responsiveness. Methods. We mapped sPRS variants to genes using regulatory annotation tools and performed pathway enrichment analysis. Single-cell RNA sequencing (scRNA-seq) was conducted on peripheral blood mononuclear cells (PBMCs) from patients stratified by sPRS and matched by PM2.5 exposure to identify transcriptional perturbations in response to PM2.5 exposure. In silico analyses predicted regulatory networks and small molecules that could modulate these pathways. Results. sPRS-associated genes were enriched for SMAD2/3 and MAPK signaling, implicating TGF-β1 as a key mediator of PM2.5 sensitivity. scRNA-seq revealed immune cell-specific transcriptional changes linked to inflammation. Notably, HDM2 inhibition downregulated the PM2.5-sensitive transcriptomic signature, suggesting a role in restoring glucocorticoid responsiveness. Interpretation. Our findings suggest a TGF-β1–HDM2–p53 axis may contribute to PM2.5-induced glucocorticoid resistance and identify HDM2 as a potential therapeutic target for future investigation in PM2.5-sensitive children with asthma.

overall_design: This study investigates the molecular mechanisms underlying genetic susceptibility to PM2.5 exposure in pediatric asthma. We stratified children with asthma by a previously validated PM2.5 sensitivity polygenic risk score (sPRS) into high and low sPRS groups. Peripheral blood mononuclear cells (PBMCs) were collected from subjects matched for age, sex, and ambient PM2.5 exposure levels. Single-cell RNA sequencing (scRNA-seq) was performed to characterize transcriptional changes associated with sPRS status in the context of PM2.5 exposure. The experimental design aims to identify immune cell-type–specific responses, regulatory networks, and potential therapeutic targets mediating PM2.5 sensitivity.

first: Huiqi

last: Qu

first: Cuiping

last: Hou

first: Frank

last: Mentch

first: Sharon

last: McGrath-Morrow

first: Hakon

last: Hakonarson


title: Genetically engineered ErbB2 overexpression sensitizes organoid-derived tumors to checkpoint inhibition in a syngeneic model of gastric cancer

city: Zurich

first: Genome

last: Informatics

address: Winterthurerstrasse 190

department: Functional Genomics Center Zurich (FGCZ)

country: Switzerland

institute: ETH ZURICH / University of Zurich

summary: ERBB2/HER2 is overexpressed in ~15% of gastric cancers due to amplification or mutation of the ERBB2 locus. While the tumor cell-intrinsic consequences of ERBB2 overexpression are well understood, much less is known about its effects on the tumor microenvironment. Here, we have developed genetically engineered ectopic and orthotopic syngeneic models of organoid-based gastric cancer that have allowed us to study the tumor microenvironment of ErbB2-overexpressing tumors. We find that ErbB2 drives the infiltration of CD4+ and CD8+ T-cells, which express granzymes, FasL and surface markers indicating chronic activation, and in the case of CD8+ T-cells, have undergone clonal expansion. The adoptive transfer of T-cells sorted from ErbB2-overexpressing tumors reduces the growth of ErbB2-expressing, but not control tumors in T-cell-deficient recipients. PD1-specific checkpoint blockade synergizes with an ErbB2-targeting antibody to reduce the growth of ErbB2-expressing, but not control tumors. Mechanistically, ErbB2 overexpression results in micronuclei formation and the transcriptional activation of numerous interferon-responsive genes in vitro and in vivo; mice lacking the type I interferon receptor show higher engraftment rates and lower T-cell infiltration than wildtype controls. The combined data indicate that ErbB2, perhaps by driving micronuclei formation, has immunogenic properties that manifest in the form of increased T-cell infiltration and expansion, and can be exploited therapeutically by combining PD1-directed checkpoint blockade with ErbB2-targeted therapy.

overall_design: Samples were extracted from 3D cultured ErbB2 overexpresssion murine gastric corpus organoids and its ctrl orangoids which transduced with a empty vector.Bulk RNA sequencing was conducted at the Functional Genomics Center Zürich. Total RNA was extracted using the Qiagen RNeasy Mini Kit according to the manufacturer’s protocol. Library preparation was performed with the Illumina TruSeq mRNA Library assay, following standard procedures. Sequencing was carried out on the Illumina NovaSeq 6000 using the S1 Reagent Kit v1.5 (100 cycles), and demultiplexing was performed with the Illumina bcl2fastq Conversion Software. The number of reads per library ranged from 17 million to 42.7 million

first: Jiazhuo

last: He

first: Lydia

last: Kirsche

first: Zuzana

last: Nascakova

first: Franceso

last: Manfredi

first: Chiara

last: Magnani

first: Giovanni

last: Papi

first: Flora

last: Azizi

first: Peter

last: Leary

first: Anne

last: Müller


title: Sequencing of total RNA from human naevi and adjacent normal skin

city: WOOLLOONGABBA

first: Mitchell

last: Stark

state: QLD

address: 37 Kent St

department: Frazer Institute

country: Australia

institute: The University of Queensland

summary: Using whole-transcriptome sequencing, we evaluated 32 naevi (and adjacent perilesional skin) characterised by histopathology and dermoscopic patterns, to reveal a novel gene-set enriched in actively growing naevi.

overall_design: Human naevi were surgically excised, and both the lesions and adjacent normal skin (perilesional tissue) were microdissected. Total RNA was extracted from naevi and perilesional samples, and RNA-seq libraries were prepared and subjected to high-throughput deep sequencing.

first: Joachim

last: Torrano

first: Darren

last: Smit

first: Harald

last: Oey


title: A Period1 inducer specifically advances circadian clock in mice

city: Kanazawa

first: Hajime

last: Tei

state: Ishikawa

address: Kakuma-cho

department: Science and Technology

institute: Kanazawa University

summary: West-to-east transmeridian flights are more disruptive than east-to-west ones due to challenges in advancing the human circadian clock. Transient mammalian Period1 (Per1) induction was predicted to predominantly advance clock phase in our previous work. Here, we unravel a specific Per1 inducer, Mic-628, enabling abrupt phase advance in mouse behavioral rhythms, regardless of the timing of oral administration. Mic-628-treated mice re-entrain to phase-advanced light-dark cycles significantly faster. The direct interaction between Mic-628 and CRYPTOCHROME1 (CRY1) does not simply inhibit CRY1 repressor activity. Instead, the interaction facilitates the CLOCK-BMAL1 assembly, ensuring highly specific induction via a tandem E-box motif upstream of the Per1 promoter. Importantly, Mic-628-driven Per1 induction is repressed by PER1 itself. Mathematical modeling indicates that both the CRY1- and PER1-mediated transcriptional regulation fixes the phase of Per1 induction irrespective of intake time, thereby predominantly advancing the clock phase. These findings underscore the potential of selective Per expression as a therapeutic approach for human circadian rhythm disorders.

overall_design: Examination of poly(A)+ enriched RNAs in NIH3T3 cells 1 day after treatment with Mic-628 or vehicle.

first: Yoshifumi

last: Takahata

first: Nobuya

last: Koike

first: Rika

last: Numano

first: Koichiro

last: Uriu


title: Palmitic Acid Activates c-Myc via Dual Palmitoylation-dependent Pathways to Promote Colon Cancer

city: Hangzhou

first: Xuejing

last: Shao

address: 866, Yuhangtang Road

department: Zhejiang University

institute: College of Pharmaceutical Sciences

summary: Transcriptional factor c-Myc plays a crucial role in various types of cancer including colon cancer. c-Myc is hyperactivated during the tumorigenesis and malignant progression of colon cancer, but the mechanisms underlying this transcriptional activation remain largely unknown. Considering that colon cancer is constantly exposed to intestinal metabolites, we wonder whether they play a key role in c-Myc transcriptional activation. Here, we reveal that palmitic acid is essential for the transcriptional activation of c-Myc during both inflammation-driven tumorigenesis and tumor progression. Notably, c-Myc is activated by palmitic acid in dual palmitoylation-dependent pathways  “passive activation under palmitic acid exposure” and “proactive activation through palmitic acid uptake”. Finally, exploiting metabolic addiction to palmitic acid as a vulnerability, we propose a promising therapeutic strategy inhibiting palmitoyltransferase ZDHHC9 and fatty acid transporter FATP2 which exerts favorable therapeutic effects against colon cancer. Together, these findings not only uncover a crucial biological role of palmitic acid on c-Myc activation depending on palmitoylation at distinct stages of colon cancer, but also highlights targeting ZDHHC9 and FATP2 as a promising option for colon cancer treatment.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: gene expression profiling analysis of RNA-seq data for colonic tissue derived from C57BL/6 mice fed with normal diet (ND), a diet containing 7.5% or 15% palmitic acid (PAD) or classical high-fat diet (HFD), along with cyclic treatment of DSS as well as HCT116 subcutaneous xenografts in nude mice supplied by ND or 7.5% PAD

first: Meidan

last: Ying

first: Wenxin

last: Du


title: In vitro growth of Toxoplasma gondii tachyzoites on different host cell lines selects for changes in efficiency of invasion and parasite surface antigen gene expression

city: Stanford

first: Adit

last: Naor

address: 300 Pasteur Drive Stanford, D305 Fairchild Building

institute: Stanford

summary: Toxoplasma gondii is remarkable for its intermediate host range which includes most warm-blooded animals so far tested. Being such a generalist poses challenges for how the parasite can be optimized for growth in cell types that might be radically different in their metabolism and other aspects, including host defenses and/or microenvironments. To explore how the parasite might adapt to finding itself in a different host, we started with a Type II line of Toxoplasma gondii (ME49) that had been grown for at least the past 20 years exclusively in vivo. This line was then used to repeatedly infect two cell lines in vitro, human foreskin fibroblasts and Madin-Darby bovine kidney cells. After at least 70 such passages in one or other host cell type, the resulting lines were compared with respect to growth differences, secretion of an important adhesin (MIC2), and transcriptome. The results showed that passage on these two host cell lines results in profound and reproducible differences in parasite phenotype, including attachment/invasion, MIC2 secretion, and gene expression. The transcriptomic differences were especially pronounced for parasite surface antigen genes. The implications of these results for how Toxoplasma gondii deals with its breadth of possible intermediate hosts are discussed

overall_design: Toxoplasma gondii  ME49 grown in different host cell lines for different durations

first: John

last: Boothroyd