title: Pan-cancer analysis combining RNA-seq reveals that ZNF25 contributes to glioma progression mainly through modulating PI3K-AKT signaling pathway

status: Public on May 01 2026

first: Xiaohong

middle: Huang

last: Yi

state: Sichuan

address: 1166 Liutai Avenue, Wenjiang District, Chengdu City

department: School of Basic Medical Science

institute: CDUTCM

summary: Background: ZNF25, a member of zinc finger proteins with KRAB domains family genes, is a transcription factor. Previous reports showed it is a biomarker of ovarian cancer. However, there are rarely reports about ZNF25 in other types of cancer, and its underlying mechanisms are not yet clear. Methods: Based on The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), IntOGen, TIMER, TIMER2, TISIDB, MethSurv, TISIDB, and Cistrome Data Browser (CDB) databases, we adopted bioinformatics methods to excavate the potential tumor genomic features of ZNF25, including dissecting the correlation with prognosis, gene mutation, immune cell infiltration, and DNA methylation in different tumors, and evaluated the association with tumor heterogeneity and stemness, and co-expression with Tex cells, chemokines chemokine receptors, and immunomodulators in pan-cancer. Additionally, we knocked down ZNF25 in U87-MG cells and performed RNA-seq analysis, then differential expression genes (DEGs) were further analyzed and visualized, like GO, and KEGG to interpret the biological significance. Results: The results show that ZNF25 has early diagnostic potential and was associated with the immune infiltration of different tumors. ZNF25 is associated with most tumor immune-infiltrating cells in pan-cancer, especially in glioma. Additionally, ZNF25 correlates with DNA methylation, tumor heterogeneity, Tex, and stemness in many types of cancers, like glioma. Besides, our findings demonstrate a close relationship between ZNF25 and mutated IDH1 in gliomas. Furthermore, our experiments showed that ZNF25 is involved in cancer pathways, mainly in PI3K-AKT and MAPK pathways.Conclusion: Through pan-cancer analysis combined with RNA-seq data, we discovered that ZNF25 might influence the progression of glioma mainly via the PI3K-AKT signaling pathway, and suggested that ZNF25 could serve as an indicator for tumor diagnosis, treatment, and prognosis across various types of tumors, including glioma.

first: Xianwen

last: Zhang

first: Lijun

last: Huang

first: Yumei

last: Wang


title: Evidence for coordinate epigenomic roles for CTCF and histone H3.3 in K27M diffuse midline gliomas [ChIP-seq]

status: Public on Mar 24 2026

city: Sacramento

first: Paul

last: Knoepfler

state: CA

address: 2425 Stockton Blvd, Room 633

department: Cell Biology and Human Anatomy

country: USA

institute: University of California Davis

type: Genome binding/occupancy profiling by high throughput sequencing

summary: In this study we identified and characterized key chromatin domains in diffuse midline glioma cells, looking at well known types of domains including super enhancers, bivalent domains, and H3K4me3 broad domains as well as the chromatin states identified by chromHMM. In this context, we identified a key role for CTCF in maintaining H3K27me3 levels at bivalent domains, and demonstrated that the H3.3K27M mutation affects both CTCF localization and H3K27me3 at these regions. We further characterized a functional interaction between H3.3 and CTCF in diffuse midline glioma cells, finding that the H3.3K27M mutation affects CTCF localization, leading to an expansion of CTCF-bound domains including a large number of ectopic CTCF binding sites found in H3.3K27M but not WT cells. We also found that CTCF knockdown increases cell viability in H3.3K27M cells, and affected the expression of a set of genes highly enriched in active chromatin states and likely important for some of the oncogenic properties of these cells. Together, our results identified complex chromatin domains defined by combinations of epigenetic modifications, which may have implications for designing therapy regimens that include multiple epigenetic drugs to more effectively target the numerous changes in chromatin observed in glioma cells with H3.3K27M. We also defined an important role for the structural protein and transcription factor CTCF in influencing the epigenetic landscape and transcriptome in the context of the H3.3K27M mutation in diffuse midline glioma cells.

overall_design: H3K4me3 ChIP-seq was performed in duplicate in DIPG Line XIII cells.

first: Rachel

last: Klein


title: Wogonin precondition of MSCs improved their therapeutic efficiency on the colitis through promoting glycolysis

city: guangzhou

first: Wu

middle: Meng

last: ye

state: Guangdong

address: Guangzhou Yuexiu

department: The Biotherapy Center,

country: China

institute: the Third Affiliated Hospital, Sun Yat-Sen University

type: Expression profiling by high throughput sequencing

summary: In order to clarify the underlying mechanism of wogonin improving the therapeutic effect of MSCs in DSS-induced colitis

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of MSC treatment with the presence and obsence of wogonin for 24h, and Comparative gene expression profiling analysis of RNA-seq data between them.

first: Yanwen

last: Peng

first: Mengye

last: Wu

first: Cuiping

last: Li

first: Xue

last: Zhou


title: Aging promotes a RAGE-dependent increase in breast cancer metastasis

status: Public on Mar 23 2026

city: Washington

first: Jiaxiang

last: Tao

state: DC

address: 3970 Reservoir Road NW

department: Oncology

institute: Georgetown University

summary: Breast cancer incidence and mortality increase with age, but the mechanisms linking aging to metastasis remain unclear. Most preclinical studies use young animal models, limiting insight into how the aged microenvironment influences cancer. Here, we show that aging markedly increases breast cancer metastasis in multiple mouse models, and this effect is dependent on host expression of the Receptor for Advanced Glycation End-products (RAGE). Aging increased tumor RAGE ligand levels, including S100A8/9 and AGEs, and induced RAGE-dependent changes in inflammatory, EMT, angiogenic, and extracellular matrix gene programs in tumors. Circulating cytokines and S100A8/9 from aged hosts promoted tumor cell invasion, which was suppressed by RAGE or S100A8/9 inhibition. In human breast cancers, elevated AGER expression and enrichment of aging- and RAGE-associated transcriptional signatures correlated with poorer survival, especially in older patients. These findings identify RAGE as a mechanistic link between aging and metastasis and a potential therapeutic target in older patients.

overall_design: RNA-seq profiling of primary mouse breast tumors from wild-type and RAGE knockout young (3 months old) and aged (21 months old) mice.

first: P.

last: Miller

first: J.


title: Selective targeting of endothelial and perivascular ROCK2 reverses liver fibrosis in  pigs and human patients

city: Chengdu

first: Bi-Sen

last: Ding

address: Wuhou District, Renmin three paragraphs

department: The West China Second UniversityHospital of Sichuan University

institute: Sichuan University

summary: Investigation of ROCK2 distribution and expression in NPC subpopulations of fibrotic and healthy human and minipig livers.

sample_organism:
Homo sapiens
Sus scrofa

platform_organism:
Homo sapiens
Sus scrofa

overall_design:
This study was designed to analyze the distribution of different cell types and gene expression in fibrotic and healthy liver tissues obtained through surgical biopsy
We performed single-cell RNA sequencing on liver non-parenchymal cells (NPCs) derived from humans and minipigs to evaluate ROCK2 expression and therapeutic effects.
Human samples: NPCs were isolated from fibrotic liver tissues and healthy controls obtained during surgical resection.
Minipig samples: A MASH model was established using a high-fat, high-sugar diet combined with intraperitoneal injection of carbon tetrachloride for 3 months. Paired liver biopsies were collected at two timepoints: pre-treatment (after 3 months of induction) and post-treatment (after 9 months of ROCK2 inhibitor administration).

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

first: Chengju

last: Xiao

first: Yan

last: Hu


title: B cell derived type I interferon promotes T cell effector function during chronic infection

city: Parkville

first: Jan

last: Schroeder

state: Victoria

address: Peter Doherty Institute Melbourne

department: DMI

country: Australia

institute: University of Melbourne

summary: B cells are the most abundant lymphocytes and play a central role in humoral immunity. However, their impact on T cell responses, in particular of CD8+ T cells, remains incompletely understood. Here, we identify a critical role for B cells in promoting CD8+ T cell responses to chronic, but not to acute, viral infections. We identify B cells as key type I interferon (IFN-I) producers and demonstrate that the T cell requirement for B cell-derived IFN-I is cell-intrinsically regulated by T cell receptor (TCR) stimulation, with T cells encountering high antigen loads showing an increased dependency on IFN-I to acquire effector function. In the absence of B cells, exhausted T cells displayed more severe functional impairments in effector differentiation and cytokine production, resembling tolerized T cells. Overall, we uncover a previously unrecognized role for B cells in supporting effective CD8+ T cell in chronic infection responses through the provision of IFN-I.

overall_design: Single cell rna sequencing of P14 T cells primed in spleen or lymph nodes of WT or uMT mice

first: Catarina

last: Gago da Graça

first: Leonie

last: Heyden

first: Anna

middle: F

last: Lindermann

first: Sining

first: Annika

last: Poch

first: Minh-Hanh

middle: T

last: Nguyen

first: Nhat-Truong

middle: A

last: Huynh

first: Yuxi

last: Cao

first: Danielle

last: Chen

first: Carlson

last: Tsui

first: Zeinab

last: Abdullah

last: Schröder

first: Jayendra

last: Singh

first: Axel

last: Kallies

first: Daniel

last: Utzschneider


title: The RNA-seq data of root tissue from transgenic poplar

city: Beijing

first: Han tian

last: Wei

address: Chinese Academy of Forestry

institute: Chinese Academy of Forestry

summary: The root tissues of WT, bHLH58-OE#20, bhlh58-KO#6, bHLH151-OE#17, bhlh151-KO#40, and bhlh58/151-KO#32 plants were collected for RNA-seq analysis with three biological replicates.

overall_design: To find the upstream and downstream regulatory genes associated with root phenotype, we performed transcriptome sequencing.

first: Han-tian

first: Jian-jun


title: Membrane insertion of mitochondrial-encoded proteins regulates ribosome decoding speed

status: Public on Mar 27 2026

city: Göttingen

first: Peter

last: Rehling

address: Humboldtallee

department: Cellular Biochmeistry

country: Germany

institute: University medical center Göttingen

summary: The human mitochondrial genome encodes thirteen subunits of the oxidative phosphorylation system essential for energy metabolism to drive cellular activities. Translation of eleven mRNAs by membrane-bound ribosomes is coupled to insertion of the nascent polypeptides into the inner membrane aided by the OXA1L insertase. To this end, the mechanism of membrane insertion of nascent polypeptides and the functional link to the translation process are not understood. Here we applied ribosome profiling to assess translation dynamics in combination with cryo-EM analyses of a COX1 ribosome nascent chain complex to visualize co-translational folding of the nascent chain. We find that the membrane topology of the translation product impacts translation speed and that positioning of amphipathic helices in the ribosome vestibule induces structural changes, correlating with translation stalling events. Thus, our findings reveal a tight link between translation process and folding and membrane insertion of nascent polypeptides at the inner mitochondrial membrane.

overall_design: Ribosome profiling and Cryo-EM analysis of human mitochondrial co-translational insertion machinery

first: Thomas

last: Schöndorf

first: Valentyn

last: Petrychenko

first: Ilgin

last: Kotan

first: Luis Daniel

last: Cruz-Zaragoza

first: Drishan

last: Dahal

first: Cong

last: Wang

first: Tanja

last: Gal

first: Sven

last: Dennerlein

first: Günter

last: Kramer

first: Niels

last: Fischer


title: Retrospective analysis reveals the early origin and development of pulmonary perivascular cells

city: Rotterdam

first: Beatrice

last: Tan

address: Dr. Molewaterplein 40

department: Developmental Biology

country: Netherlands

institute: Erasmus MC

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Retrospective analysis reveals the early origin and development of pulmonary perivascular cells [scRNA-seq]

summary: The pulmonary vasculature develops in close association with the airways and this network expands through the interactions between endothelial cells and the surrounding mesenchymal cells, the pericytes. Emerging evidence suggests that pericytes play a significant role in various lung diseases, such as congenital diaphragmatic hernia and chronic obstructive pulmonary disease. However, characterizing pericytes remains challenging, impeding our understanding of their exact role in lung development and disease. Therefore, we used a novel cell tracing technology based on a bacterial DNA cytosine methyltransferase (Dcm) fused to RNA polymerase II (DCM-TM) to methylate active genes. The doxycycline inducible Dcm-PolII fusion protein was activated at specific time points during gestation, while the epigenetically labeled genes were analyzed at later time points. This retrospective cell tracing was coupled to single-cell RNA sequencing to track the development of mouse pulmonary pericytes at the single cell level. This revealed the paths to differentiation of perivascular progenitors into pericytes and vascular smooth muscle cells. Temporal analysis uncovered dynamic gene expression profiles during pericyte differentiation, highlighting pathways crucial for pulmonary vascular development. Further analysis showed intricate signaling interactions between pericyte progenitors and mature pericytes, and we validated MCAM as a bona fide pulmonary pericyte marker. Our findings challenge conventional views on pericyte origin and underscore the importance of accurate pericyte identification in developmental and disease contexts. Overall, this study enhances our understanding of pulmonary pericyte ontogeny and differentiation, offering insights into their potential as therapeutic targets in pericyte-associated lung diseases.

overall_design: We performed scRNA-seq and MeD-seq on DCM-time machine mice to track the development of mouse pulmonary pericytes.

first: Isabel

last: Sreeram

first: Ruben

middle: G

last: Boers

first: Joachim

middle: B

first: Robbert

last: Rottier


title: Retrospective analysis reveals the early origin and development of pulmonary perivascular cells [MeD-seq]


title: VLA-4 Agonist Promote Engraftment and Cell Immune Reconstitution of Allogeneic Hematopoietic Stem Cells

city: Shanghai

first: Qiaomei

last: He

address: No. 100 Haining Road, Hongkou District, Shanghai

department: Hematology

institute: Shanghai General Hospital Affiliated to  Shanghai Jiao Tong University

summary: Successful engraftment and early immune reconstitution of donor hematopoietic stem cells (HSCs) are crucial for allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about how to promote implantation and early immune reconstitution of HSCs through regulating its own functions. Here, we identified very-late antigen (VLA-4) as a pivotal target in regulating HSC implantation. Critically, we screened out a VLA-4 agonist, which could promote the implantation and long-term hematopoietic reconstitution of donor HSCs in a mixed donor chimerism (MDC) mouse model and serial xenotransplantation model of human CD34+ cells from umbilical cord blood (UCB). Competitive transplantation mouse model and limited dilution assay for UCB CD34+ cells revealed that VLA-4 agonist could enhance the self-renewal capacity of HSCs and increase the number of severe combined immunodeficient (SCID)-repopulating cells (SRCs) to five-fold in vivo. Furthermore, the VLA-4 agonist could facilitate early post-transplant cell immune reconstitution by enhancing T cell output of HSCs. VLA-4 agonist regulates HSC functions and lymphoid progenitor differentiation through affecting the ERK1/2 phosphorylation pathway, whereas may not increase the risk of leukemia transformation. These findings indicate that the VLA-4 agonist holds a great clinical translational potential in enhancing engraftment of HSCs and early cellular immune reconstitution following allo-HSCT.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Single-cell transcriptome sequencing analysis on bone marrow cells from clinical samples and mouse models in two states, from mixed donor chimerism (MDC) to full-donor chimerism (FDC), was performed to explore the key regulatory target affecting HSC implantation after allo-HSCT. The effects of the agonists that modulate this target on HSC implantation and function after transplantation were investigated in a novel MDC mouse model, competitive transplantation mouse model and serial umbilical cord blood (UCB) xenograft transplantation model. To gain further insight into the effects of VLA-4 A2 on the process of HSC implantation after allo-BMT, we conducted scRNA-seq on BM lineage negative cells from VLA-4 A2- and vehicle-treated MDC mice at 2Ws and 5Ws after transplantation.

first: Xi

last: Sun

first: Lin

last: Chen

first: Jun

last: Yang

first: Huixian

last: Wu

first: Shixuan

last: Tang

first: Liping

last: Wan

first: Yan

last: Zhang

first: Bo

last: Zhou

first: Fang

first: Xianmin

last: Song


title: Bortezomib increases immunotherapy efficacy through enhancement of  STING and IFN-γ signaling in lung adenocarcinoma

city: 湖北省 / 武汉市 / 硚口区

first: Yu

last: Xi

state: hubei province

address: 同济医学院附属同济医院

department: Department of Thoracic Surgery

institute: huazhong University of science and technology

summary: BTZ has been reported to block cell proliferation and promote apoptosis of NSCLC cells. However,  the clinical trails of BTZ alnoe or BTZ combinated with other chemotherapy have failed. Here,  we reported that BTZ enhanced the anti-tumor efficacy of PD1/PDL1 blockade therapy in a Lewis lung carcinoma (LLC) tumor model. In both in vitro and in vivo assay, our data showed that BTZ activated STING pathway and increased the responsiveness of tumor cells to IFN-γ through the upregulation of surface IFN-γ receptor I (IFNGR1), which contributed to the superior anti-tumor efficacy of BTZ in combination with PD1/PDL1 inhibitors in lung adenocarcinoma.

overall_design: Subcutaneous LLC tumors in triplicates that grew in C57BL/6 mice were uesd. The mice were divided into 3 groups: isotype; anti-PDL1 alone; BTZ+anti-PDL1

first: Kelin

last: Meng

first: Taiyan

last: Yu

first: Congjian

last: Wang


title: Microtubule anchoring and coupling of CD20 to the RhoA/Rock1 pathway

status: Public on Mar 20 2026

city: Freiburg

first: Geoffroy

last: Andrieux

address: Breisacherstr 153

institute: University clinics Freiburg

summary: CD20 is a B cell-specific four-helix transmembrane protein and a prominent target of therapeutic anti-CD20 antibodies. We have recently described that CD20 is localized within a membrane nanocluster harboring the IgD class B cell antigen receptor (IgD-BCR) where it functions as a gatekeeper for the resting state of naïve human B lymphocytes. How CD20 exerts its gatekeeper function is not yet known. Using Ramos and human peripheral blood B cells, we show here that the serine/threonine kinase PKCδ, constitutively phosphorylates serine residues at the cytosolic tails of CD20. The phosphorylated CD20 becomes a target for 14-3-3 adaptor proteins that link CD20 to the RhoA GDP/GTP exchange factor GEF-H1 and the microtubule (MT) network controlling the stability of the IgD-BCR nanocluster. Binding of anti-CD20 antibodies results in MT disassembly and the replacement of the GEF-H1/CD20 complex by a RhoA-GTP/ROCK1/CD20 complex which drives actomyosin contractility. Our study suggests that CD20 not only maintains the resting state, but also orchestrates the MT/actin switch in active B lymphocytes. This could have implications for treatment with anti-CD20 antibodies and may help to optimize therapeutic protocols

overall_design: To investigate the gatekeeper function of protein kinase C delta (PKCδ) we generated two different Ramos PKCδ KO cell lines using CRISPR-Cas system, exploring the differences in regulation of activation on B lymphocytes.

first: Cindy

middle: E

last: Lee

first: Claudio

last: Mussolino

first: Klaus

last: Warnatz


title: miR-99b-5p inhibition drives apoptosis and tumor shrinkage in triple-negative breast cancer: Functional characterization through AGO2-RIP-seq and mechanistic insights

city: Ankara

first: Efe

last: Dalli

address: Dogol Street

country: Turkey

institute: Ankara University

summary: Background: Dysregulated microRNAs (miRNAs) are critical contributors to breast cancer biology, yet the functional roles of many remain incompletely understood. miR-99b-5p has been widely characterized as a tumor-suppressive miRNA in numerous cancer types, where its expression is consistently reduced in tumors compared with normal tissues. In contrast, our analyses of breast cancer datasets revealed a unique expression pattern: miR-99b-5p is significantly upregulated in breast tumors, suggesting a context-dependent oncogenic function. In this study, we identified miR-99b-5p as an oncogenic driver in triple-negative breast cancer (TNBC). Methods and Results: TCGA-based expression profiling confirmed its elevated levels in breast tumors. Functional assays demonstrated that downregulation of miR-99b-5p in TNBC cells inhibits proliferation and induces apoptosis, indicating a critical role in sustaining tumor cell survival. To elucidate the molecular mechanisms underlying this activity, we performed AGO2-RNA immunoprecipitation followed by high-throughput sequencing (AGO2-RIP-Seq), enabling unbiased identification of miR-99b-5p-associated transcripts. Pathway enrichment analyses revealed that its direct targets converge on apoptotic regulation, cell-cycle control, and ubiquitin-mediated protein degradation. Mechanistic validation through qRT-PCR, Western blotting, and luciferase assays confirmed that miR-99b-5p modulates the TRAIL-R signaling pathway via DR5 and BAK, attenuating apoptotic signaling. In vivo studies using xenograft models established with MDA-MB-231 cells stably expressing miR-99b-5p knockdown showed marked tumor regression, further supporting its oncogenic role. Conclusion: Collectively, these findings establish miR-99b-5p as a context-specific oncogenic miRNA in breast cancer and a promising therapeutic target, particularly for TNBC, where targeted treatment options remain limited.

overall_design: This study aims to identify the direct targets of miR-99b-5p in triple-negative breast cancer (TNBC) using Argonaute-2 based RNA-immunoprecipitation sequencing (AGO2-RIP-seq). We utilized the MDA-MB-231 cell line, which was transfected with either a miR-99b-5p mimic to overexpress the miRNA or a scrambled negative control. To capture the miRNA-target mRNA complexes, immunoprecipitation was performed using an anti-AGO2 antibody, with IgG used as a non-specific binding control. The AGO2-RIP-seq was conducted with two independent biological replicates for each condition (miR-99b-5p mimic vs. Scrambled Control). The enrichment of target mRNAs in the AGO2-IP fraction compared to the control was analyzed to map the miR-99b-5p-dependent targetome. Complementary gene expression analysis and functional assays (proliferation, apoptosis, and luciferase reporter assays) were integrated to validate the biological impact of the identified targets.

first: Senem

last: Noyan

first: Kubra

middle: N

last: Kaplan-Ilhan

first: Muge

middle: O

last: Demirtas

first: Begum

first: Bora

last: Ergin

first: Rabia

last: Sen

first: Hakan

last: Gurdal

first: Bala

last: Dedeoglu


title: Mitochondria-lysosome coupling contributes to lysosome acidification and aging

city: Novato

first: Qingqing

last: Liu

state: California

address: 8001 Redwood Blvd

institute: Buck Institute - Novato, CA

summary: Nearly all cellular processes are pH dependent. The acidic pH inside the lysosome (vacuole in yeast) is essential for cellular content degradation, signaling, and autophagy. Defect in lysosome/vacuole acidification is a conserved hallmark of aging and age-related diseases. Traditionally, lysosome/vacuole is thought to import free protons (H⁺) from the surrounding neutral cytosol. In this study, we uncovered a previously unrecognized, conserved lysosome/vacuole acidification mechanism, involving lysosomal/vacuolar uptake of H+ pumped out by mitochondrial electron transport chain through membrane contacts between mitochondria and lysosomes/vacuoles. Aging/senescence-associated disruption of mitochondria-lysosome/vacuole contacts causes lysosomal/vacuolar de-acidification, which can be reversed by expressing a linker to connect these organelles and through an asymmetry-dependent rejuvenation process in daughter cells. Preserving lysosomal acidification in senescent human cells prevents the induction of major senescence-associated secretory phenotype factors and enhances autophagic flux. These findings reshape our current understanding of the mechanisms underlying lysosomal/vacuolar (de-)acidification in both young and aged/senescent cells.

overall_design: Senescent IMR90 cells with and without an engineered Mito-Lyso linker are induced by exposing to a single dose of 10 Gray ionizing radiation (IR) for 9 minutes according to the treatment condition in Campisi lab. After IR, placed cells back to the incubator and changed medium every 48 hrs. Assays for senescent cells were done 10 days after IR. Pre-senescent IMR90 cells are with less than 15-17 passages.

first: Sungmin

last: Yoo

first: Alice

last: Zhang

first: Liying

last: Li

first: Hetian

last: Su

first: Lingraj

last: Vannur

first: Chuankai

last: Zhou


title: snRNA-Seq analysis of islets from WT mice treated with or without 0.5mM Glucosamine

status: Public on Mar 19 2026

city: Jerusalem

first: Yael

last: Riahi

address: Kyriat Hadassah

country: Israel

institute: The Hebrew University

summary: In diabetes, hyperglycemia drives the progression of b-cell failure and multi-organ complications. Prolonged exposure to high glucose stimulates mTORC1, resulting in impaired glucose metabolism and exacerbation of ER stress and inflammation. However, the precise mechanism by which glucose regulates mTORC1 activity in diabetes remains unclear. We performed metabolic labeling with 13C6- glucose in diabetic animals treated with or without the SGLT2 inhibitor (SGLT2i) dapagliflozin or insulin, followed by targeted metabolomics and metabolic flux analysis. We found that tissue glucose concentrations strongly correlate with glucosamine, rather than with other glucose or amino acid metabolites. Plasma glucosamine levels are increased in patients with impaired fasting glucose (IFG) and type 2 diabetes (T2D) and are inversely correlated with b-cell function. Glucosamine is synthesized by amine group transfer from glutamine to glucose, which enhances O-GlcNAcylation (O-GlcN) of mTORC1- regulating proteins, including Raptor, via O-GlcNAc transferase (OGT), subsequently activating mTORC1. We propose that the glucosamine-mTORC1 pathway is a key mediator of glucose toxicity in diabetes.  We studied the role of glucosamine in mediating beta-cell glucotoxicity.

overall_design:
To investigate the molecular mechanisms underlying glucotoxicity in beta cells, we performed snRNA-seq analysis. Pancreatic islets were isolated from three WT mice, using a split-sample design: islets from each mouse were divided equally into two groups, receiving either 0.5 mM Glucosamine or vehicle control for 24 hours.
This yield three paired biological replicates per condition.
Following treatment, islets were dissociated into single-cell suspension and nuclei were subsequently isolated.

first: Erez

last: Dror

first: Ziv

last: Teselpapa

first: Gil

last: Leibowitz


title: CapMux: a Snakemake pipeline for early demultiplexing of split-pool scRNA-seq data into sample-resolved outputs

city: Vilnius

first: Denis

last: Baronas

address: Saulėtekio al. 7

country: Lithuania

institute: Vilnius University

summary: Single-cell RNA sequencing methods based on split-pool combinatorial barcoding enable high-throughput profiling, yet sample identity is often encoded during early barcoding steps rather than through the library index. Consequently, reads from multiple biological samples remain pooled, complicating per-sample analysis and selective extraction of samples of interest. Here, I present CapMux, a Snakemake-based pipeline for processing split-pool scRNA-seq data from raw sequencing files to sample-resolved outputs. CapMux supports workflows starting from either BCL files or FASTQ files and reconstructs sample identity by integrating sub-library index information with the experiment-specific barcoding plate layout. The pipeline was developed for the CapSeq method but is configurable for related scRNA-seq combinatorial barcoding designs through specification of barcode positions and experimental layout. CapMux resolves pooled data into outputs for each sample, enabling independent quality control summaries, mapping statistics, count matrices, and downstream visualizations. Runtime benchmarking indicated that secondary demultiplexing step added only a modest computational overhead. Together, these results show that CapMux provides a practical and adaptable framework for recovering sample-level resolution from split-pool scRNA-seq data.

overall_design: CapSeq scRNA-seq experiment performed on Neuro-2a, NIH/3T3, and mESC cell lines. Each cell line was distributed across four BC1 plate columns: Neuro-2a cells in columns 1–4, NIH/3T3 cells in columns 5–8, and mESCs in columns 9–12.


title: Plasma Olink Explore HT of primary glomerular disease patients

status: Public on Mar 22 2026

city: Seoul

first: Jae-ik

last: Oh

address: 101, Daehak-ro, Jongno-gu

department: Translational Medicine

country: South Korea

institute: Seoul National University College of Medicine

summary: This study utilized large-scale systemic proteome profiling to identify distinct protein signatures that can non-invasively differentiate major subtypes of primary glomerular disease and provide insights into their underlying mechanisms.

overall_design: Plasma proteome profiling was performed using the Olink Explore HT platform, which quantified 5,416 proteins from 147 discovery samples and 85 validation samples encompassing major subtypes of primary glomerular disease (FSGS, IgAN, MCD, MN) and healthy controls.

first: Kyeonghun

last: Jeong

first: Jung Hun

last: Koh

first: Jin Gyeong

last: Kwon

first: Semin

last: Cho

first: Jeong Min

first: Yaerim

last: Kim

first: Hajeong

last: Lee

first: Hyun Je

first: Jeonghwan

first: Jung Pyo

first: Ji In

last: Park

first: Jung Tak

first: Kwangsoo

first: Sehoon

first: Dong Ki


title: Palmitoleic acid promoted by BMPR2 signaling primes CD169 macrophages and alleviates liver fibrosis [albcre_bmpr2]

first: Jinkun

last: Zhong

address: No. 130, Dong'an Road, Xuhui District, Shanghai

institute: Fudan University

summary: Bone morphogenetic proteins (BMPs) participate in the energy metabolism. BMP receptor type 2 (BMPR2) is expressed in the liver. Whether BMPR2 is involved in the pathophysiology of nonalcoholic fatty liver disease (NAFLD) has not been studied. In this study, we analyzed the RNA-sequence data of several patient cohorts and found that BMPR2 expression decreases at the stages of advanced fibrosis. A mouse model featuring BMPR2 knockout demonstrated that BMPR2 knockout in the liver produced profibrotic effect upon long-term high-fat and high-fructose (HFF) diet challenge. BMP signaling promoted biosynthesis of unsaturated fatty acids, which was repressed under BMPR2 knockout condition. The most affected unsaturated fatty acid, palmitoleic acid (POA), was found to activate CD169 macrophages. Moreover, CD169 macrophages were revealed to have high levels of lysosomal enzyme along with matrix metalloproteinase 8, which degraded collagen and alleviated fibrosis. Our study demonstrated that BMPR2 influences over the progression of liver fibrosis induced by the HFF diet through fatty acid-regulated CD169 macrophages. POA-primed macrophages might be a potential therapeutic strategy for the treatment of liver fibrosis.

overall_design: RNA-seq profling of livers from liver-specific knockout of BMPR2 mice(LKO) and wildtype mice(WT).

first: Hong

last: Ma

first: Qilin

last: Peng

first: Mengyuan

last: Dai

first: Linyuan

last: Wang

first: Jianan

first: Danchun

last: Huang

first: Yang

last: Liu

first: Yan

last: Tang

first: Wei

last: Xu

first: Qi-qun

first: Shuwen

last: Qian


title: Palmitoleic acid promoted by BMPR2 signaling primes CD169 macrophages and alleviates liver fibrosis [PM_POA_PA]

overall_design: RNA-seq profling of wildtype peritoneal macrophages treated with palmitoleic acid(POA) and palmitic acid(PA).


title: PWWP-mutants of the transcriptional cofactor JASPer divert promoter and enhancer activities and suppress position effect variegation in Drosophila [Hi-C]

status: Public on Mar 26 2026

city: Freiburg im Breisgau

first: Derek

last: Atkinson

address: Stübeweg 51

institute: Max Planck Institute for immunobiology and epigenetics

summary: Su(var) genes control heterochromatin establishment and maintenance in Drosophila melanogaster. Through a new Su(var) screen, we identified Su140 and Su113 as very strong Su(var) mutants that are epistatic over Su(var)3-9 in the In(1)wm4h PEV rearrangement. Both Su140 and Su113 encode point mutations in the PWWP domain of the transcriptional cofactor JASPer that has described functions in protecting gene activity in euchromatin. In JasperSu140/Su140 and JasperSu113/Su113 nuclear cycle (NC14) mutant embryos, heterochromatic marks (H3K9me2 and H3K9me3) are reduced, while activating histone modifications (H3K4me1 and H3K27ac) become enriched at heterochromatin. Whereas epitope-tagged wild-type JASPer accumulates over H3K36me3-positive regions in gene bodies, mutant JASPerSu140 is redistributed to cis-regulatory motifs (CRM) in promoters and enhancers. At genes, JASPerSu140 relocates to transcriptional start sites (TSS). Also, one third of developmentally regulated enhancers, including the white enhancer, show enrichment for JASPerSu140 and display elevated levels of eRNA in JasperSu140/Su140 NC14 embryos. In addition, JasperSu140/Su140 mutants induce a partial decompaction of the heterochromatin compartment containing the In(1)wm4h rearrangement and activate satellite repeat expression. Together, these data define Jasper mutants as novel Su(var) genes and highlight the importance of maintaining the balance between euchromatic and heterochromatic domains for controlling position effect variegation.

overall_design: HiC of wm4h and Su140 NC14 embryos, 6 replicates per conditon

first: Francesco

last: Cardamone

first: Yinxiu

last: Zhan

first: Thomas

last: Jenuwein

first: Nicola

last: Iovino


title: SP1 antagonizes H3K27me3 to shape chromatin landscapes for RNA polymerase II recruitment during gastrulation [RNA-seq]

city: chongqing,china

first: xipeng

last: shen

address: yixueyuan road NO.1

department: basic medicine

institute: CQMU

summary: Following implantation, the epiblast undergoes gastrulation to form the three germ layers, a process requiring precise temporal control of developmental gene expression. However, the mechanisms governing RNA polymerase II (Pol II) engagement at developmental gene promoters during this critical stage remain poorly understood. Here, we present a genome-wide analysis of Pol II occupancy in mouse post-implantation embryos, revealing that nearly half of bivalent promoters are bound by Pol II in a lineage-specific and temporally ordered manner. This recruitment follows a stepwise chromatin remodeling cascade, with initial deposition of H3K27me3, followed by H3K4me3 acquisition and Pol II engagement. Through genetic perturbation, we show that KMT2B promotes Pol II loading via H3K4me3 deposition, whereas the Polycomb component EED restricts this process by maintaining H3K27me3. Notably, we identify the transcription factor SP1 as a critical facilitator of Pol II recruitment at bivalent loci. SP1 binding coincides with reduced H3K27me3 levels and enhanced Pol II occupancy, and its loss leads to chromatin re-silencing and transcriptional failure. Together, our findings establish a chromatin-based regulatory framework in which SP1 and histone modifications cooperatively license the transcriptional activation of developmental genes during germ layer formation.

overall_design: To evaluate the gene expression level in different germ layers in E6.5 and E7.5 embryos, Smart-seq2 was perform in normal development embryos as well as in gene knockout E6.5 epiblast including Jarid2, Kmt2b, Eed and Sp1 with control.

first: Xipeng

last: Shen

first: Yuting

last: Wen

first: Yunlong

last: Xiang


title: Integrated transcriptomic and metabolomic analyses reveal the regulatory network underlying NtGSTU10-mediated nicotine synthesis and transport in tobacco

status: Public on Mar 18 2026

city: guiyang

first: yudan

last: zhou

address: West Campus of Guizhou University, Huaxi District

institute: Guizhou University

summary: Nicotine is the major alkaloid in tobacco and plays a key role in determining tobacco quality. Previous studies have shown that overexpression of NtGSTU10 enhances nicotine accumulation in tobacco hybrids; however, the molecular mechanisms underlying this process remain largely unclear.

overall_design: In this study, we investigated the regulatory role of NtGSTU10 in nicotine synthesis and distribution using integrated transcriptomic and metabolomic analyses in NtGSTU10-overexpressing tobacco plants. Nicotine content and distribution between roots and leaves were quantified, and global transcriptional and metabolic profiles were analyzed to reveal molecular changes associated with NtGSTU10 overexpression. The results showed that NtGSTU10 overexpression was associated with increased nicotine accumulation in leaves and reduced nicotine levels in roots, resulting in significantly higher nicotine transport coefficients compared with wild-type plants. Transcriptomic analysis revealed coordinated changes in genes involved in nicotine biosynthesis, transport, and secondary metabolism. Metabolomic profiling indicated significant alterations in amino acid metabolism, nicotinic acid and nicotinamide metabolism, purine metabolism, sugar metabolism, and alkaloid biosynthesis pathways. Integrated transcriptome–metabolome analysis further identified coordinated regulation of glutathione metabolism, ABC transporters, and MATE transporter–encoding genes. Overall, these results reveal a regulatory network associated with NtGSTU10-mediated nicotine biosynthesis and transport, providing new insights into the molecular mechanisms underlying nicotine metabolism in tobacco.

first: Yudan

last: Zhou


title: Hippo signaling differentially regulates distal progenitor subpopulations and their transitional states to construct the mammalian lungs

status: Public on Mar 17 2026

city: San Francisco

first: Erica

last: Yao

address: 555 Mission Bay Blvd. South, Box 3118

institute: University of California, San Francisco

summary: Lung cells from Lats1f/f; Lats2f/f; SftpcCre/+ and littermate control mice were collected at embryonic day 14.5 (E14.5) and 17.5 (E17.5) for multiomics.

overall_design: Lungs were isolated from E14.5 and E17.5 Lats1f/f; Lats2f/f; SftpcCre/+ and littermate control embryos and dissociated into single-cell suspensions, washed with PBS, and frozen. On the day of scRNA-seq, cells were thawed, then incubated with antibodies against CD45 and TER119 to label immune cells and blood cells, respectively. The samples were sorted by FACS, and CD45- TER119- live cells were collected. Nuclei were isolated from the collected cells and used for snATAC-seq/snRNA-seq. Libraries were prepared using the 10x Genomics Chromium Next GEM Single Cell Multiome ATAC + Gene Expression Reagent Kit.

first: Kuan

last: Zhang

first: Madhuri

last: Basak

first: Youssef

last: Zaher

first: Pao-Tien

last: Chuang


city: Kawasaki

first: Yuko

last: Ogata

state: Kanagawa

address: 6-21-1 Nagao, Tama-Ku

department: Division of Chemical Information, Research Center for Chemical Information and Management

country: Japan

institute: National Institute of Occupational Safety and Health, Japan

summary: Gene expression analysis of human lymphoblastoid TK6 cells exposed to the carcinogen 3-methylcholanthrene (3-MCA) was conducted. The information entropy of the transcriptome was measured to assess whether a change with biological significance occurred in TK6 cells exposed to 3-MCA. Pathway and literature analyses for DEGs were also performed.

overall_design: RNA-Seq was performed. TK6 cells obtained from JCRB Cell Bank were incubated with 0, 0.0004, 0.04 and 4 micrograms per milliliter 3-methylcholanthrene for 24 hours.


summary: Lung cells from Lats1f/f; Lats2f/f; SftpcCre/+ and littermate control mice were collected at embryonic day 14.5 (E14.5) and 17.5 (E17.5) for scRNA-seq.

overall_design: Lungs were isolated from E14.5 and E17.5 Lats1f/f; Lats2f/f; SftpcCre/+ and littermate control embryos and dissociated into single-cell suspensions, washed with PBS, and frozen. On the day of scRNA-seq, cells were thawed, then incubated with antibodies against CD45 and TER119 to label immune cells and blood cells, respectively. The samples were sorted by FACS, and CD45- TER119- live cells were collected and used for scRNA-seq. Libraries were prepared using 10x Genomics Chromium GEM-X Universal 3' Gene Expression Kit (v4).


title: Genome-scale metabolic modelling uncovers cell-type specific signatures associated with APOE variants

city: Bethesda

first: Priyanka

middle: S.

last: Narayan

state: Maryland

address: 9000 Rockville Pike

department: National Institute of Diabetes and Digestive and Kidney Diseases

institute: Natonal Institutes of Health

summary: Metabolic dysregulation is a key feature of Alzheimer’s disease (AD) pathogenesis. The ε4 variant of APOE gene (APOE4), coding for the lipid-transporter apolipoprotein E, is the strongest genetic risk factor for late-onset AD. Previous studies have investigated how APOE4 disrupts specific metabolic pathways within different cell types. In this study, we followed a broad, metabolite-centric approach to investigate how APOE4 reshapes cellular metabolism in a cell type-specific manner based on transcriptome and metabolome data. We integrated transcriptomics data from an isogenic set of iPSC-derived neurons, astrocytes, and microglia harboring APOE3 or APOE4 genotypes into a human genome-scale metabolic model. From this model, we identified metabolic pathways that differed between APOE3 and APOE4 cells. We then used metabolomics data from the same iPSC-derived cell types to validate pathways identified by the transcriptomic analysis. In addition to confirming previous reports of disrupted cholesterol and fatty acid metabolism, we also identified bile acid biosynthesis, folate metabolism, and thyroid hormone metabolism as novel pathways dysregulated in APOE4 cells. Moreover, we were able to detect similar metabolic dysregulation in human post-mortem transcriptomic data. By integrating transcriptomic and metabolomic data, our approach can enhance understanding of biological mechanisms associated with APOE4-associated metabolic dysregulation in AD.

overall_design: RNA-seq profiling of iPSC-derived microglia cells of APOE3 and APOE4 genotypes.

first: Dilara

last: Uzuner Odongo

first: Linling

last: Cheng

first: Linda

last: Yang

first: Roxan

last: Stephenson

middle: S

first: Tunahan

last: Çakır

first: Madhav

last: Thambisetty


title: RNA sequencing of nasal lavage samples from mock- and Streptococcus pneumoniae-infected infant mice

status: Public on Mar 16 2026

city: Manhattan

first: Chaitra

last: Sreenivasaiah

state: NY

address: 227 E 30th St

department: Applied Bioinformatics Laboratory

institute: NYU Langone Health

summary: Nasopharyngeal colonization by Streptococcus pneumoniae (Spn) is common and often asymptomatic, yet prolonged colonization increases the risk of transmission and invasive pneumococcal disease, particularly early in life. Host immune pathways that prevent persistent colonization remain poorly understood. Here, we examined how IL-1R and IL-17RA signaling shape host transcriptional responses during pneumococcal colonization of the upper respiratory tract. Using a mouse model of Spn colonization, we performed bulk RNA-sequencing on nasal lavages from mock-treated and Spn-colonized wild-type, Il1r1-/- and Il17ra-/- mice. In wild-type mice, colonization induced robust upregulation of inflammatory and innate immune gene programs, whereas many of these responses were attenuated in Il1r1-/- and Il17ra-/- mice. Taken together, this analysis demonstrates that IL-1R and IL-17RA signaling are required for full activation of host transcriptional responses that limit persistent Spn colonization.

overall_design: We performed gene expression profiling of nasal lavage samples from mock or Streptococcus pneumoniae-infected WT, Il1r1-/- and Il17ra-/- infant mice, with n=6-7 per group.

first: Teniola

last: Idowu

first: Jeffrey

last: Weiser


title: Cell Death Modalities Modulate Inflammatory and Regenerative Programs in Zebrafish Sensory Organs

city: Kansas City

first: Shiyuan

middle: (Cynthia)

last: Chen

state: MO

department: Computational Biology

institute: Stowers Institute for Medical Research

summary: Regeneration is triggered by cells dying due to various types of injuries. However, it remains unclear whether different types of cell death elicit distinct regeneration responses. Here, we systematically profile dynamic transcriptional responses of macrophages and lateral line cells to different cell death modalities during zebrafish sensory hair cell regeneration. We show that chemogenetically induced programmed hair cell death triggers a diminished inflammatory response compared to pharmacologically induced cell lysis, characterized by minimal neutrophil recruitment, distinct transcriptional profiles in phagocytosing macrophages and reduced expression of injury-responsive genes in lateral line cells. Nevertheless, regeneration ultimately converges on a shared set of regeneration-specific genes. Importantly, preventing immune cell recruitment enhances injury-induced support cell proliferation in response to programmed, but not unprogrammed cell death, highlighting cell death-dependent regenerative outcomes following immune cell inhibition. Our findings demonstrate that distinct forms of cell death trigger distinct molecular events, with implications for tailoring regenerative therapies to specific injury contexts.

overall_design: Macrophages and lateral line cells were isolated using FACS sorting and their transcriptomes analyzed using scRNA-seq.

first: Daniela

last: Muench

first: Tatjana

last: Piotrowski


title: SP1 antagonizes H3K27me3 to shape chromatin landscapes for RNA polymerase II recruitment during gastrulation

first: xipeng

last: shen

overall_design: We firstly tested the sensitivity of antibodies to capture total RNA Pol II using low-input Hela cell  using STAR chromatin immunoprecipitation–sequencing (STAR ChIP-seq). To investigate the dynamics of RNA Pol II in mouse post-implantation embryos, we separated mouse E6.5 embryos into epiblast (Epi), visceral endoderm (VE), and extra-embryonic ectoderm (ExE), and E7.5 embryos into ectoderm (Ect), mesoderm (Mes), endoderm (End), and ExE and generated ChIP-seq data for Pol II and Ser2p. To investigate the factors involved in regulating Pol II occupancy at bivalent genes, we utilized CRISPR-Cas9 technology combined with electroporation of fertilized eggs to obtain gene knockout embryos including Jarid2, Kmt2b, Eed and Sp1. ChIP-seq of transcription factors Pol II, Ser2p and SP1 as well as histone modifications H3K4me3 and H3K27me3 were performed.

first: Xipeng

last: Shen

first: Yuting

last: Wen

first: Yunlong

last: Xiang


title: Effect of Sox2-activation on transcriptomic profiles of murine lung tumors

city: Houston

first: Fredrik

middle: Ivar

last: Thege

state: Texas

address: 6565 MD Anderson Blvd

department: Translational Molecular Pathology

institute: UT MD Anderson Cancer Center

summary: To investigate the effect of Sox2-activation during lung tumorigenesis, we treated CRISPRa competent PPKS (KRAS(LSL-G12D//wt); TP53(flox/flox); Rosa26(LSL-SAM/wt)) mice with CMV-Cre/U6-sgRNA(MS2) encoding lentivirus carrying Sox2-targeted or non-targeted sgRNA. Tumors were harvested at survival endpoint and transcriptomic reprogramming was assessed with RNA-seq.

overall_design: 4 PPKS mice were treated with Sox2-targeting CMV-Cre/U6-sgRNA(MS2) lentivirus and 4 PPKS mice were treated with non-targeting CMV-Cre/U6-sgRNA(MS2) lentivirus through nasal instillation. Tumors were harvested at survival endpoint and total RNA was extracted. mRNA-sequencing libraries were generated, sequenced and bioinfomatically analyzed.

first: Anirban

last: Maitra

first: Sonja

last: Woermann


title: Lineage and Organ Signals Sequentially Build Organ Intrinsic Nervous Systems [Spatial Transcriptomics]

city: New Haven

first: I-Uen Yvonne

last: Hsu

state: Connecticut

address: 100 College Street

department: Neuroscience

institute: Yale University School of Medicine

summary: Organ intrinsic nervous systems (OINSs) are critical components of the body–brain axis, coordinating visceral organ function with systemic physiological control. Despite their importance, how these distinct neural architectures arise from a common neural crest cell (NCC) origin has remained unclear. Here, we present a systems-level, cross-organ analysis of OINS development, integrating lineage tracing, 3D imaging, single-cell transcriptomics, and genetic perturbations across heart, pancreas, intestine, and lungs. We show that differences in NCC migratory trajectories prefigure the spatial architecture of OINSs, laying the foundation for organ-specific patterning. In contrast, molecular identity emerges largely in response to local environments, indicating that extrinsic cues play a major instructive role. Using in vitro co-cultures, we demonstrate that organ-derived cues reprogram intrinsic neurons toward organ-specific transcriptional profiles and direct neuronal differentiation, with extracellular matrix (ECM) contact identified as a central mediator. In vivo, ECM–integrin signaling supports intrinsic cardiac neuron neurogenesis, while ECM crosslinking stabilizes their stereotyped ganglionic organization. Together, these findings reveal that OINS diversity arises through a dual logic: lineage programs prefigure spatial frameworks, while organ-specific cues instruct final molecular identities and architectural precision. This work establishes a conceptual paradigm for how organs actively build their own nervous systems, illuminating principles that underpin body–brain integration.

overall_design: Hearts from E14.5 Wnt1-Cre;lox-Sun1-GFP mice were acutely dissected and freshly frozen in OCT. Cryosections (10 μm) were cut using a cryostat (Thermo Fisher Scientific) and mounted onto the 10x Visium Spatial Gene Expression Slide. Tissue sections were imaged on a Leica SP8 confocal microscope with a 16× objective to obtain tissue morphology and locate ICNS ganglia. Sequencing libraries were prepared following the manufacturer’s protocol (10x Visium) and sequenced using an Illumina NovaSeq 6000 S4 sequencer at Yale Center for Genomic Analysis.

first: Rui

last: Chang

first: Le

last: Zhang


title: Effect of Myc-activation on transcriptomic profiles of murine pancreatic tumors

summary: To investigate the effect of Myc-activation during pancreatic tumorigenesis, we treated CRISPRa-competent PPKS (KRAS(LSL-G12D//wt); TP53(flox/flox); Rosa26(LSL-SAM/wt)) mice with CMV-Cre/U6-sgRNA(MS2) encoding lentivirus carrying Myc-targeted or non-targeted sgRNA. Tumors were harvested at survival endpoint and transcriptomic reprogramming was assessed by RNA-seq

overall_design: 5 PPKS mice were treated with Myc-targeting CMV-Cre/U6-sgRNA(MS2) lentivirus and 5 PPKS mice were treated with non-targeting CMV-Cre/U6-sgRNA(MS2) lentivirus through retrograde ductal injection. Tumors were harvested at survival endpoint and total RNA was extracted. mRNA-sequencing libraries were generated, sequenced and bioinfomatically analyzed.


title: MAIT cell enrichment in Lynch syndrome is associated with immune surveillance and colorectal cancer risk

city: Philladephia

first: Hairu

last: Yang

address: Philadelphia, PA 19104

department: Division of Gastroenterology and Hepatology

institute: University of Pennsylvania Perelman School of Medicine

summary: Tissue microenvironment characteristics associated with elevated risk of colorectal cancer (CRC) in Lynch syndrome (LS) are poorly characterized. We applied the multimodal single cell sequencing platform ExCITE-seq to define the colonic cellular composition and transcriptome of LS carriers with and without a history of CRC compared with general population controls. Our analysis revealed widespread remodeling in LS that included striking expansion of epithelial stem and progenitor cells, and loss of fibroblast populations. Although clonally expanded and terminally exhausted CD8 T cells were more prominent in individuals with a history of CRC, LS carriers without CRC displayed enrichment of cytotoxic mucosal-associated invariant T (MAIT) cells associated with CCL20 expression in epithelial progenitors, validated by orthogonal techniques including demonstration of a protective function in a murine model of CRC. These findings highlight cellular features that distinguish LS carriers and suggest a protective role of MAIT cells in human CRC surveillance.

overall_design:
We performed ExCITE-seq on fresh, non-tumor proximal colonic biopsies collected from three age- and sex-matched groups: 10 LS carriers without CRC (LS), 6 LS carriers with a prior history of CRC (disease-free for over two years and not on treatment at the time of collection; LS-CRC), and 8 non-LS controls (undergoing routine screening colonoscopy; CON)

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

first: Ken

last: Cadwell

first: Meenakshi

last: Bewtra

first: Bryson W

last: Katona


title: Lineage and Organ Signals Sequentially Build Organ Intrinsic Nervous Systems [scRNA-seq]

overall_design: For single-cell RNA sequencing of organ-intrinsic neuronal cells, the heart, lungs, pancreas and intestines were dissected from Wnt1-Cre;lox-tdTomato, Phox2b-Flpo;frt-tdTomato, or Baf53b-Cre;lox-L10GFP mouse embryos at E12.5, E14.5, E16.5, E18.5 and P56. Fluorescently labelled neuronal cells were enriched by Fluorescence-activated cell sorting (FACS) on a BD FACS Aria cell sorter. For experiments comparing heartnear and heartfar regions, E14.5 atrial regions containing Wnt1-Cre;lox-L10GFP labelled ICNS cells were separated from atrial regions lacking ICNS. Each region was dissociated into single-cell suspensions. For coculture experiments, cardiac atria and intestines were dissected from E13.5 Phox2b-Flpo;frt-tdTomato embryos. FACS-purified enteric neurons were cocultured with non-neuronal cardiac or intestinal cells for 4-5 days before harvesting for single-cell RNA sequencing. Single-cell cDNA libraries were prepared using the Chromium Single Cell 3’ V3 reagent kit and sequenced using an Illumina NovaSeq 6000 sequencer.


title: Integrated Perturb-seq and Computational Modeling Identifies KAT6A-Menin-DOT1L Synergy and Associated Gene Program as Therapeutic Targets in Acute Myeloid Leukemia [RNA-Seq]

status: Public on Mar 25 2026

city: Birmingham

first: Changde

last: Cheng

state: Alabama

address: 1824 6th Ave S, WTI 510G

department: Department of Medicine - Hematology & Oncology

institute: The University of Alabama at Birmingham

summary:
Background:
Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by genetic and epigenetic dysregulation. Despite advances in targeted therapies against individual epigenetic regulators, clinical responses are often transient due to complex compensatory mechanisms. Identifying functional interactions between chromatin regulators and their associated transcriptional programs represents a promising strategy to overcome resistance and enhance therapeutic efficacy.

Results:
Using Perturb-seq combined with computational modeling and machine learning approaches, we systematically investigated 16 key epigenetic regulators across the Menin-MLL, Polycomb, and histone acetyltransferase complexes in MOLM-13 cells. Single-cell transcriptomic analysis of 31,015 cells revealed 17 distinct gene programs with differential impacts on AML pathogenesis. We identified strong synergy between KAT6A and the Menin-DOT1L axis in regulating oncogenic pathways, particularly gene program P-15 (Pro-Differentiation Program), which significantly correlates with favorable clinical outcomes in both TCGA and Beat-AML cohorts. Notably, P-15 showed high expression in NPM1-mutated AML and remission-stage patients but was suppressed in TP53-mutated cases with poor prognosis. Validating our computational predictions, dual inhibition of Menin (VTP-50469) and KAT6A (WM119, a preclinical compound) demonstrated significant therapeutic synergy in MOLM-13 cells, reducing the IC50 from 35nM to 12nM. Conversely, PCGF1 disruption conferred resistance to DOT1L inhibition, revealing a novel mechanism of therapeutic resistance. Bulk RNA-seq analysis of combination treatments confirmed that dual KAT6A-Menin inhibition uniquely modulates specific gene modules associated with myeloid differentiation.

Conclusions:
Our integrated experimental-computational approach, distinct from prior studies examining individual epigenetic regulators in isolation, identifies the KAT6A-Menin-DOT1L axis as a critical regulator of AML transcriptional programs in MLL-rearranged leukemia and reveals gene program P-15 as both a favorable prognostic biomarker and potential therapeutic target. These findings provide mechanistic insights into epigenetic regulation in AML and establish a framework for developing rational combination therapies targeting cooperative epigenetic dependencies while preventing compensatory resistance mechanisms.

overall_design: mRNA profiles in MOLM-13 cells with DMSO, VTP50469 , WM119 and Combination treatment.

first: Sajesan

last: Aryal

last: Lu


title: The PGD2/DP2 axis promotes pro-inflammatory responses but attenuates an antigen-presenting role of human basophils

status: Public on Apr 29 2026

city: Headington

first: Jian

last: Luo

state: Oxford

address: 69 Headley Way

department: Nuffield Department of Medicine

country: United Kingdom

institute: University of Oxford

summary: Basophils are distinct blood leukocytes that express immunoglobulin (Ig) E receptor FcR1 and can be activated by IgE. Their roles in asthma, particularly IgE-independent effects, remain incompletely understood. Human basophils highly express the prostaglandin D2 (PGD2) receptor 2 (DP2; also known as chemoattractant receptor homologous molecule expressed on Th2 cells, CRTH2). Here we explore the PGD2/DP2 axis as an alternative pathway for basophil activation. Basophils are enriched in patients with severe eosinophilic asthma, correlating with eosinophil counts but not IgE levels. PGD2/DP2 stimulation promots basophil recruitment, activation, and the production of histamine, leukotrienes, and type 2 cytokines. RNA sequencing and further in vitro experiments reveals that, although PGD2 and IgE share some signalling pathways and functions, they induce distinct gene transcriptional signatures. Interestingly, PGD2 downregulats major histocompatibility complex class I-related gene protein (MR1) and attenuates basophil antigen-presentation to mucosal associated invariant T (MAIT) cells, leading to reduced IFN- production. These findings highlight the PGD2/DP2/basophil axis as a contributor to asthma, particularly in IgE-low conditions, and suggest it as a potential therapeutic target for related diseases.

overall_design: RNA-seq profiling of human basophils treated with media, PGD2, PGD2+QAW039, IgE/anti-IgE.

first: Wentao

last: Chen


title: Translesional DNA Polη Bypass of LANA-DNA Crosslinks Ensures KSHV Episome Persistence and Tumor Growth

city: Philadelphia

first: Paul

middle: M

last: Lieberman

state: Pennsylvania

address: 3601 Spruce Street

institute: The Wistar Institute

summary: The episome maintenance of DNA tumor viruses depend on their viral-encoded sequence-specific DNA binding proteins. We show here that the Kaposi’s Sarcoma- Associated Herpesvirus (KSHV) episome maintenance protein LANA can form DNA- protein crosslinks (DPCs) with the terminal repeat (TR) DNA in a cell cycle dependent manner. Targeted shRNA screening identified translesional repair DNA polymerase Polh as necessary for the stability of KSHV TR DNA and viral episome maintenance. We found that Polh co-immunoprecipitates and co-localizes with LANA nuclear bodies. Inhibiting the enzymatic activity of Polh by small molecule provided selective cell killing of KSHV+ B-cells and inhibited tumor progression in mice xenografts. Mechanistically Polh inhibition results in both single and double strand breaks at the KSHV TR due to unresolved LANA-DNA cross-links and replication fork collapse. These findings reveal a new mechanism of viral episome maintenance by DPC coupled to TLS DNA polymerases and identify Polh as a potential target for inhibition of KSHV latent infection in proliferating tumor cells.

sample_organism:
Homo sapiens
Human gammaherpesvirus 8

platform_organism:
Homo sapiens
Human gammaherpesvirus 8

overall_design: DNA-seq of single and double strand breaks isolated from the genomic DNA of a KSHV infected DLBCL cell line treated with polH inhibitor, PNR-7-02.

first: Jayaraju

last: Dheekollu

first: Coltin

middle: J

last: Albitz

first: Anjali

last: Pathania

first: Frederick

last: Keeney

first: Samantha

last: Soldan


title: Temporal control of sgRNA library activation unlocks large-scale in vivo CRISPR screens

city: Boston

first: Teng

last: Teng

state: MA

address: 201 Brookline Ave Suite 901

institute: Tango Therapeutics

summary: Functional genomics screens have revealed cancer gene dependencies, but cell culture misses vulnerabilities driven by the tumor microenvironment. We implemented CRISPR-StAR (Stochastic Activation by Recombination), an inducible pooled screening system that activates gene knockout after tumor engraftment and provides matched internal controls for guide-level normalization. Using barcode-embedded sequencing and Bayesian analysis, we screened a 30,000-sgRNA library in A549 xenografts and achieved reproducible dropout and enrichment phenotypes using just ~30 tumors. Across additional xenograft models, single tumors yielded reliable functional annotation for ~1,000 genes leveraging within-tumor normalization. Comparing in vivo and in vitro screens uncovered tumor-suppressor effects detectable only in vivo; for example KMT2C and KMT2D knockouts produced contrasting tumor growth and transcriptional programs. Together with our R analysis package, CRISPR-StAR enables scalable in vivo dependency mapping that complements in vitro resources and reduces animal use up to sevenfold versus conventional dropout screens, improving overall methodological rigor at genome-scale clonal resolution.

overall_design: Cas9-expressing cells were infected with a CRISPR-StAR library containing 29,068 guide RNAs targeting druggable genes (A549 cells) or a minipool validation library (both CRISPR-StAR and CRISPR-UMI format) containing 910 guide RNAs (A549, SW1573 and H460 cells) and subsequently engrafted in NOG mice for in vivo growth period. Terminal tumor samples were collected and extracted for gDNA. Custom PCR amplication were carried out and purified to generate NGS sequencing libraries. Guide enrichment or depletion was determined by NGS sequencing and processed by custom pipeline to generate gRNA and UMI counts.

first: Silvia

last: Fenoglio

first: Yi

last: Yu

first: James

last: Tepper

first: Lauren

last: Grove

first: Alborz

last: Bejnood

first: Samuel

middle: R

last: Meier

first: Ashley

middle: H

last: Choi

first: Hsin-Jung

last: Wu

first: Annabel

last: Devault

first: Shangtao

last: Liu

first: Binzhang

last: Shen

first: Tenzing

last: Khendu

first: Hannah

last: Stowe

first: Esther

middle: C

last: Uijttewaal

first: Minjie

first: Brian

last: Haines

first: Erik

last: Wilker

first: Alan

last: Huang

first: Daniel

last: Schramek

first: Ulrich

last: Elling

first: Xuewen

last: Pan

first: Jannik

last: Andersen


title: In vivo CRISPR activation screening of tumor formation in murine pancreas and lung.

first: Fredrik

last: Thege

summary: We performed in vivo CRISPR activation screening of tumor formation in the pancreas and lung by treating CRISPRa competent PPKS (KRAS(LSL-G12D//wt); TP53(flox/flox); Rosa26(LSL-SAM/wt)) mice with CMV-Cre/U6-sgRNA(MS2) lentivirus containing the Onco1 sgRNA guide library. Tissues were harvested at different timepoints (6 days, 4 weeks, 8 weeks and survival endpoint). HEK293T cell cultures were transduced with the same libraries to generate normalization controls. Library plasmid DNA (pDNA) was sequenced as controls.

sample_organism:
Escherichia coli
Homo sapiens
Mus musculus

overall_design: 24 PPKS mice were treated with the Onco1 library through retrograde ductal injections to the pancreas and 29 mice were treated through nasal instillation. HEK293T cells were transduced with the Onco1 library at an MOI < 0.3. Genomic DNA was extracted from tissues and cell cultures. Sequencing libraries were generated using direct PCR of guide sequence containing region.

first: Anirban

last: Maitra

first: Sonja

last: Woermann


title: Transcriptomic features of GFP+ RPE cells in Serpine-Gfp heterozygous mice at 2 months II

status: Public on Apr 30 2026

first: David

last: McGaughey

state: MD

address: 10 Center Dr

department: NEI

institute: NIH

summary: Heterogeneous degeneration of retinal pigment epithelium (RPE) leads to irreversible blindness in diseases associated with macular atrophy. However, the underlying mechanisms of regional RPE degeneration remain poorly understood. To address this gap, this study first identifies a novel RPE subpopulation through the spatial, transcriptomic, and functional analyses, thereby contributing to the understanding of the heterogeneity of degenerative RPE cells. Specifically, omics analyses in human and macaque RPE reveal a peripheral RPE cell population with high SERPINE3 expression, while SERPINE3-GFP knock-in mice show comparable expression patterns. In addition, SMART-seq2 analysis further distinguishes transcriptomic profiles between GFP-positive and GFP-negative RPE cells. Under oxidative stress, SERPINE3 expression increases, and GFP-positive cells exhibit improved survival and reentry into the cell cycle. Notably, genetic studies indicate that SERPINE3 is essential for the oxidative stress resistance of GFP-positive cells. Moreover, loss of SERPINE3 results in regional RPE degeneration and increased microglial accumulation in aged mice. Mechanistically, proteinase screening and co-immunoprecipitation indicate that SERPINE3 targets Caspase-1. Importantly, delivery of SERPINE3 via AAV-Serpine3 prevents RPE degeneration in a geographic atrophy disease model. These findings advance the understanding of RPE heterogeneous degeneration and highlight SERPINE3 as a novel protective factor with therapeutic potential for macular atrophy.

overall_design: RNA-seq profiling of peripheral GFP positive cells and central non GFP RPE cells

first: Huirong

last: Li

first: Robert

last: Hufnagel

first: Vincent

last: Kunze

first: Wei

first: Bin

last: Guan


title: Widespread non-Mendelian inheritance of DNA methylation patterns in mice [ONT Muscle]

city: Baltimore

first: Adam

last: Davidovich

address: 855 N. Wolfe Street

institute: Johns Hopkins University

summary: We performed long-read ONT sequencing on two Collaborative Cross mouse strains and their F1 crosses. Allele-specific methylation analyses revealed widespread and diverse patterns of intergenerational epigenetic inheritance. Included among these are a large number of non-Mendelian inheritance patterns, many of which have not previously been observed in naturally occurring mammalian genomes.

overall_design: ONT sequencing was performed on muscle DNA from two Collaborative Cross mouse strains and their F1 crosses.

first: Danila

last: Cuomo

first: Hang

last: Su

first: Sandeep

last: Kambhampati

first: Qingqing

last: Gong

first: Alexandra

last: Naron

first: Rakel

last: Tryggvadottir

first: Leonard

last: McMillan

first: Kasper

middle: D

last: Hansen

middle: W

last: Threadgill

first: Andrew

middle: P

last: Feinberg


title: Single nucleus chromatin accessibility Profiling on the human metabolic dysfunction associated steatotic liver disease samples

city: Guangzhou

last: He

address: No. 9 XingDaoHuanBei Road, Guangzhou International Bio Island, Guangzhou 510005, Guangdong Province, China

department: Department of Basic Research

institute: Guangzhou National Laboratory

summary: Single-nucleus Assay for Transposase-Accessible Chromatin with sequencing (snATAC-seq) in human mapping of chromatin accessibility in specific cell clusters profiled alterations in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) samples compared to normal controls, providing insights into cell-type-specific epigenetic changes associated with MASLD.

overall_design: Normal and MASH human livers samples (each have 6 replicates) were analyzed with snATAC-seq (10x Genomics platform)

first: Biying

last: Zhu

first: Yang

last: Xiao

first: Bing

last: Chen

first: Chen


title: Integrative functional genomics reveals transcriptional regulatory function of risk alleles for metabolic liver disease

summary: Genome-wide association studies (GWAS) have identified nearly 100 loci associated with metabolic dysfunction-associated steatotic liver disease (MASLD), but the molecular functions of these variant alleles remain elusive, particularly when they occur in non-coding regions. Here we profiled the chromatin landscape of liver nuclei from 12 individuals with varying stages of metabolic liver disease, which provide a global regulatory program in liver. Then we used massively parallel reporter screen to identify differential activity variants (DAVs). The target genes of these DAVs were delineated by expression quantitative trait loci (eQTLs), chromatin loops and single-cell CRISPRi screening. These multimodal integration analyses provide insights into the regulatory mechanisms of MASLD progression driven by genetic risks.

sample_organism:
Escherichia coli
Homo sapiens

platform_organism:
Escherichia coli
Homo sapiens

overall_design: MASLD-associated variants were obtained from the GWAS Catalog and relevant publications. SNPs in LD, with MAF > 5% and R² > 0.8 were also collected.  Finally, 126 bp sequence centered on 5,369 variants was synthesized and inserted into MPAR plasmid library, following by transfecting into HepG2 and LX-2 cells for MPRA experiment. Differential activity variants were detected from MPRA data by compare the MPRA activity between reference allele and alternative allele.

last: Li


title: Widespread non-Mendelian inheritance of DNA methylation patterns in mice [ONT Liver]

summary: We performed long-read ONT sequencing and matched RNA sequencing on two Collaborative Cross mouse strains and their F1 crosses. Allele-specific methylation and expression analyses revealed widespread and diverse patterns of intergenerational epigenetic inheritance. Included among these are a large number of non-Mendelian inheritance patterns, many of which have not previously been observed in naturally occurring mammalian genomes. Targeted ONT sequencing of F2 crosses of the same Collaborative Cross strains enabled further characterization and validation of these epigenetic inheritance patterns, including distinguishing those patterns mediated by cis- or trans-acting regulatory factors.

overall_design: ONT and RNA sequencing were performed on liver DNA and RNA, respectively, of two Collaborative Cross mouse strains and their F1 crosses. Subsequent targeted ONT sequencing was performed on F2 crosses of the same Collaborative Cross strains.

first: David


title: CROP-seq of 20 MASLD-associated differential activity variants from HepG2 MPRA screen

summary: We performed CROP-seq to 20 MASLD-associated differential activity variants from HepG2 MPRA screen. This provides a powerful strategy for accurately locating the target gene pool associated with functional variants.

overall_design: We extended 150 bp upstream and downstream of plausibly causal noncoding variants from HepG2 MPRA-screen, then used FlashFry v1.15 and CRISPick to detect potential gRNAs. Top two gRNAs were synthesized and transfected to CRISPRi HepG2 cells. Then whole-transcriptome scRNA-Seq libraries and the sgRNA-enrichment libraries were separately sequenced.


title: Widespread non-Mendelian inheritance of DNA methylation patterns in mice [RNA-Seq Liver]


title: Anti-asthma drug Montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling

city: Shanghai City

first: Yali

address: No.320, Yueyang Avenue

institute: Center for Excellence in Molecular Cell Science

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

overall_design: Refer to individual Series


title: Widespread non-Mendelian inheritance of DNA methylation patterns in mice [ONT Liver - Targeted]


title: Anti-asthma drug Montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling [RNA-seq and Ribo-seq]

summary: Globally, autism spectrum disorder (ASD) affects approximately 1.0-2.5% of human newborns, with non-genetic risk factors estimated to contribute to over 50% ASD cases through yet elusive mechanisms. Montelukast (MTK), a leukotriene receptor antagonist and FDA-approved anti-asthma drug, was found to potently disrupt retinoic acid (RA) signaling, and substantially increase the risk of ASD in humans when used during pregnancy or in early childhood, according to prospective and retrospective cohort studies. Both maternal and postnatal exposure to montelukast caused autistic-like behaviors in rat offspring. Montelukast also altered brain regional patterning through disrupting RA signaling in human cerebral organoids, similar to DEAB, an established inhibitor of RA-synthesizing ALDH1As. Mechanistically, montelukast was found to directly bind to retinoic acid receptor alpha (RARα) and impair RARα heterodimer formation to disrupt RA signaling. Altogether, this work highlighted not only the developmental origin of ASD, but the utmost importance in cautioned use of medicinal chemicals during maternity or early childhood to prevent psychiatric disorders, e.g. ASD.

overall_design: Comparative gene expression profiling analysis of RNA-seq and Ribo-seq data for cerebral organoids treated with compounds (DMSO,DEAB, and MTK).

first: Rong-Gui

last: Hu

first: Shan

last: Bian

first: Ya-Li

first: Meng-Huan

last: Zhang

first: Meng-Xia

first: Zhen-Ming

last: Guo

first: Min


title: Ferroptotic tumor cells revamp tumor-associated macrophage antigen presentation to unleash immune checkpoint blockade efficacy

status: Public on Mar 15 2026

first: dingdang

last: Yu

address: No. 106, Zhongshan 2nd Road, Yuexiu District

institute: Guangdong Provincial People's Hospital

summary: Activation of antigen presentation has been shown to contribute to improved immunotherapy outcomes. Herein, we show that inducing tumor cell ferroptosis boosts anti-tumor immunity by potentiating major histocompatibility complex II (MHC-II)- dependent antigen presentation in tumor-infiltrating macrophages. Supporting our findings with multi-omics data, we reported that ferroptotic tumor-derived all-trans retinoic acid (ATRA) is a novel regulator of MHC-II in macrophages. ATRA directly targets CD38 through transcriptional factor RARα and activates master regulator TFEB to control MHC-II expression by inducing autophagy. Clinically, a ferroptosis signature is associated with better immunotherapy response. We also innovatively develop a drug-free nano-redox lever (DFNRL) to circumvent the non-specific limitations of conventional drugs, which specifically targets and disrupts glutathione metabolism in tumor cells by accepting electrons, thereby boosting ferroptosis-mediated immune stimulation. This synergizes with anti–PD-1 immunotherapy across preclinical models. Our study answers an unidentified role for ferroptosis in modulating anti-tumor immunity and provides a clinically translatable approach to enhance immunotherapy efficacy.

overall_design:
ATAC-seq profiling of BMDM cells treated with 200 nM ATRA or DMSO for 24hr;
TT-seq profiling of BMDM cells treated with 200 nM ATRA or DMSO for 24hr;
Cut&Tag for RPB1, H3K4me3 and H3K27ac using BMDM cells treated with 200 nM ATRA or DMSO for 24hr;
RNA-seq profiling of BMDM cells treated with 200 nM ATRA or DMSO for 24hr.

first: Jia lei

last: Sun

first: Dingdang

first: Shibin

first: Jimin


title: Anti-leukemic effect of MAR-3.6.2, a novel RAN inhibitor, on AML-LSCs by targeting RAN.

city: Duarte

first: WenYong

state: CA

address: 1500 E. Duarte Road

department: Cancer Biology and Molecular Medicine

institute: City of Hope

summary: The small GTPase RAN plays a role in the biogenesis of mature miR-126, which is supplied by the bone marrow arterioles to leukemic stem cells (LSCs). MiR-126 supports the homeostasis of LSCs that initiate and maintain acute myeloid leukemia (AML). While therapeutic targeting of RAN has been difficult due to its structural features, through molecular dynamics simulations and docking studies, we have identified MAR-3.6.2 as a novel allosteric inhibitor that binds in a cryptic pocket in the C-terminal domain of RAN. We showed that MAR-3.6.2 disrupted RAN interaction with its guanine nucleotide exchange factor RCC1 and prevented the nuclear switch of RAN-GDP to RAN-GTP. This in turn led to RAN nuclear retention and reduced the RAN/XPO5-mediated export of pre-miR-126, thereby limiting mature miR-126 biogenesis in endothelial cells and their exogenous supply of mature miR-126 to LSCs. In a MllPTD/WT/Flt3ITD/ITD AML murine model, MAR-3.6.2 reduced leukemia burden, prolonged survival, and decreased LSC frequency in secondary transplants. These findings highlight MAR-3.6.2 and future, potential derivates as a promising small molecule-based approach to eradicate AML LSCs via inhibition of RAN/XPO5 trafficking and block of miR-126 biogenesis.

overall_design: Transcriptome profiling of patient-drived primary AML cells trreated with vehicle vs MAR-3.6.2.

first: Truong

last: Nguyen


title: Lactylation Converts ABHD6 into a Mitochondrial Regulator that Drives Lenvatinib Resistance in Hepatocellular Carcinoma

status: Public on Mar 13 2026

city: Nantong

first: Long

address: Chongchuan DistrictNantong University No.9 Seyuan Rd

institute: nantong university

summary: Hepatocellular carcinoma (HCC) frequently develops resistance to lenvatinib, a frontline tyrosine kinase inhibitor. Resistance arises from heterogeneous mechanisms involving metabolic reprogramming and mitochondrial adaptation, implicating regulators of these processes as potential therapeutic targets.

overall_design: Here, we identified α/β hydrolase domain containing 6 (ABHD6) as a critical driver of lenvatinib resistance by perturbing mitochondrial dynamics. Ligand-binding at the S148 catalytic site allosterically controlled a molecular switch between canonical enzymatic and non-canonical scaffolding functions of ABHD6, and the pro-resistance function was independent of catalysis but required an unoccupied catalytic site. In resistant HCC, the Warburg effect elevated lactate, leading to K245 lactylation of ABHD6. This modification triggered the mitochondrial translocation of ABHD6, where it functioned as a scaffold that competitively bound the fission regulator FIS1 and displaced DRP1. Disruption of the fission machinery stabilized hyperfused mitochondria, thereby conferring lenvatinib resistance by suppressing drug-induced apoptosis and ROS generation. Both inhibiting lactate production and enforcing occupancy of the S148 site with substrates or a specific inhibitor blocked formation of the ABHD6-FIS1 complex, reactivated mitochondrial fission, and restored lenvatinib sensitivity. This study identified a lactate-driven functional switch in ABHD6 and established that targeting this allosteric mechanism is an effective therapeutic strategy to overcome lenvatinib resistance.

first: Zhiyuan

last: Tang


title: Anti-asthma drug Montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling [scRNA-Seq]

first: Yali

overall_design: Cerebral organoids were treated with different compounds (DMSO,DEAB, and MTK) and analyzed using scRNAseq.

first: Meng

last: Meng


title: Non-Mendelian inheritance of DNA methylation patterns in mice.

status: Public on Mar 14 2026

first: Adam

last: Davidovich


title: HTRA1 Mutation and Expression Regulation in Cerebral Small Vessel Disease

status: Public on Mar 11 2026

city: Shanxi

first: Shina

last: Song

address: Jiefangnan 85 Road

institute: The First Hospital of Shanxi Medical University

summary: Cerebral small vessel disease (CSVD) refers to a series of clinical, radiological, and pathological syndromes caused by various etiologies affecting small arteries, arterioles, venules, capillaries, and small veins in the brain. It can lead to cognitive impairment, stroke, gait abnormalities, and other neurological symptoms and signs. Globally, approximately 25% to 30% of strokes are caused by CSVD. The underlying mechanisms of CSVD are multifaceted, involving endothelial dysfunction, blood-brain barrier (BBB) inflammation, neuronal apoptosis, chronic cerebral hypoperfusion, and their complex interactions. Current treatments often fail to achieve satisfactory outcomes. Therefore, understanding the pathogenic mechanisms of CSVD is crucial for developing effective therapeutic strategies to mitigate its detrimental effects. The high-temperature requirement protease A-1 (HTRA1) mutations can cause hereditary CSVD. CSVD associated with HTRA1 mutations is referred to as HTRA1-associated CSVD. Homozygous HTRA1 mutations cause Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL), a rare hereditary CSVD that is inherited in an autosomal recessive manner. Heterozygous HTRA1 mutations can lead to Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy type 2 (CADASIL 2), also known as heterozygous HTRA1 mutation carriers. This condition is characterized by clinical manifestations such as stroke, cognitive impairment, gait abnormalities, alopecia, and spondylosis. To date, 35 pathogenic mutations in the HTRA1 gene have been reported, primarily exhibiting autosomal dominant inheritance. Current research mainly focuses on case reports and the potential pathogenic mechanisms associated with different mutation sites. HTRA1 mutations can lead to downregulation of HTRA1 mRNA and protein expression, thereby reducing HTRA1 protease activity. However, the specific morphological and functional changes associated with CSVD, especially those in endothelial cells, remain unclear. This study aims to explore the mutation spectrum and clinical phenotypes of heterozygous HTRA1 mutation carriers. By comparing whole-blood RNA sequencing (RNA-seq) analysis between heterozygous HTRA1 mutation carriers and healthy controls, we identify differentially expressed genes. Based on the RNA-seq results, we further investigate the effects of abnormal HtrA1 expression on the biological functions of mouse brain microvascular endothelial cells and mouse cognitive behavior. This study elucidates the role of HTRA1 in CSVD, providing insights into the pathogenesis and new therapeutic targets for patients with heterozygous HTRA1 mutations.

overall_design: This submission includes peripheral blood samples from heterozygous HTRA1 mutation carriers (HTRA1mc) and healthy controls (HC). A total of eight samples were analyzed, including four HTRA1mc patients from two independent families and four unrelated healthy controls. The experimental variable under investigation is the presence of heterozygous HTRA1 mutations. HTRA1 mutation carriers represent the experimental group, while healthy controls serve as the reference group. All samples are independent biological replicates.


title: EHMT2-mediated chromatin reprogramming in 5-fluorouracil (5-FU) resistant colorectal cancer

city: Daejeon

first: In Hwan

last: Tae

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

institute: Korea Research Institute of Bioscience and Biotechnology

summary: This study generated transcriptomic datasets to investigate the role of EHMT2 in acquired 5-fluorouracil resistance in colorectal cancer models. RNA sequencing was performed in parental and 5-FU resistant HCT116 cell lines under genetic and pharmacological modulation of EHMT2. These datasets support the findings described in the associated manuscript and provide a resource for further investigation of transcriptional mechanisms underlying chemoresistance.

overall_design: This submission includes RNA-seq samples derived from the HCT116 colorectal cancer cell line. Samples represent parental (wild-type) and 5-fluorouracil resistant cells (5fu or 5fuR) subjected to genetic modulation of EHMT2, including siRNA-mediated knockdown and corresponding siRNA control conditions. Independent biological replicates are included for each condition to enable comparative analysis of transcriptional changes associated with acquired chemoresistance.


title: Noncoding SNP rs17728461 modulates lung cancer progression via interchromosomal regulation of RAB27A expression

city: hangzhou

first: Bing

last: guo

state: zhejiang

address: cangqian street No.2318

department: school of Basic Medical Sciences

institute: HZNU

summary: To examine target genes that interact with different alleles of rs17728461 in H155 (G/G、CC) 、A549(G/G、CC、C/G、sg）cells

overall_design: H155 (G/G、CC) 、A549(G/G、CC、C/G、sg） cells were used to performed allele-specific 4C. Hind III and Dpn II were used in the experiments

first: Yan

last: Jin

first: Xiaoling

last: Tian

first: Wenxu

last: Liu


title: Single-cell transcriptome profiling of Oryza sativa node I at booting, flowering, and grain filling stages

city: KunMing

first: Hu

last: Li

state: Yunnan

address: Yunnan University

institute: agricultural college

summary: This dataset provides processed snRNA-seq gene expression data in the standard 10x Genomics CellRanger output format, including three core files: barcodes.tsv.gz (with quality-controlled nucleus-specific barcodes, matching expression matrix column order), features.tsv.gz (gene annotations: Ensembl ID, gene symbol, "Gene Expression" type, matching matrix row order), and matrix.mtx.gz (sparse MTX-format raw UMI count matrix, m×n dimensions where m=gene number, n=nucleus number, storing non-zero values as [gene_index][barcode_index][count]). These files together form a complete expression matrix and serve as fundamental input for downstream analysis via tools like Seurat and Scanpy.

overall_design: SnRNA-seq libraries were prepared using the Chromium Next GEM Single Cell 3' Reagent Kits v3.1 (10x Genomics) on a Chromium Controller. Nuclei were isolated from node I and resuspended in PBS containing 0.04% BSA. Nuclei from each developmental stage were separately loaded onto the Chromium Next GEM Chip G to generate single-cell gel beads in emulsion (GEMs), according to the manufacturer's instructions. The captured nuclei were subsequently lysed, and the released RNA underwent reverse transcription to produce barcoded, full-length cDNA. Libraries were constructed following the protocol provided by the reagent kit. The quality of the libraries was assessed using the Qubit 4.0 Fluorometer and the Agilent 2100 Bioanalyzer. Sequencing was performed on the Illumina NovaSeq 6000 platform, achieving a sequencing depth of at least 50,000 reads per nucleus, with paired-end 150 bp (PE150) reads.

first: Guijie

last: Lei


title: KIF5A downregulation in spinal muscular atrophy links axonal regeneration defects with ALS

city: Stanford

first: Yi

last: Zeng

address: 300 Pasteur Drive

institute: Stanford University

summary: Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, leading to decreased SMN levels and motor neuron dysfunction. SMN-restoring therapies offer clinical benefit, but the downstream molecular consequences of SMN reduction remain incompletely understood. Here, we demonstrate that SMN deficiency results in downregulation of KIF5A in human neurons and in a mouse model of SMA. We provide evidence that reduced SMN levels impair axon regeneration, which is rescued by KIF5A overexpression and that the RNA-binding protein SMN functions to stabilize KIF5A mRNA. These findings provide evidence of a molecular link between SMA and ALS pathophysiology, highlighting KIF5A as a new SMN target. Our findings suggest SMN-independent interventions targeting KIF5A could represent a complementary therapeutic approach for SMA and other motor neuron diseases.

overall_design: RNA sequencing profiing of human stem cell derived corticial neurons and motor neurons treated with SMN shRNA

first: Tetsuya

last: Akiyama

first: Aaron

last: Gitler


title: Unveiling Alternate Pathways for SARS-CoV-2 Infection via Extracellular Vesicle-Mediated Transfer of ACE2 and TMPRSS

city: NEW YORK

first: Ya-Wen

last: Chen

address: 1425 MADISON AVE, Icahn 13-20A, Box 1189

department: Otolaryngology

institute: Icahn School of Medicine at Mount Sinai

summary: he COVID-19 pandemic, caused by SARS-CoV-2, has underscored the urgency of understanding viral entry mechanisms to develop effective therapeutic strategies. SARS-CoV-2 primarily exploits angiotensin-converting enzyme 2 (ACE2) as its entry receptor and relies on the serine protease TMPRSS2 to prime its spike protein, enabling membrane fusion and infection. Traditionally, TMPRSS2 has been described as a cell surface protein, but our study reveals that in human lung epithelial cells, TMPRSS2 is largely absent from the plasma membrane and instead resides intracellularly. We show that TMPRSS2 is secreted together with ACE2 in extracellular vesicles (EVs) from lung epithelial cells, which are subsequently taken up by non-epithelial cells, specifically alveolar macrophages, endothelial cells, and pericytes, that do not express TMPRSS2 or ACE2 mRNA under homeostatic conditions. This EV uptake deposits ACE2 and TMPRSS2 protein onto recipient cells, equipping them for SARS-CoV-2 entry. By transferring these viral entry proteins, EVs expand the spectrum of susceptible cell types in the lung, offering a new explanation for how the virus can infect diverse cell populations and cause widespread tissue damage. Identifying EVs as vehicles for delivering functional ACE2 and TMPRSS2 across cell types reveals previously unrecognized pathway of viral entry with important implications for not only COVID-19 pathogenesis but also for other viral infections that exploit similar entry mechanisms. These findings open new avenues for therapeutic intervention aimed at disrupting EV-mediated protein transfer, potentially limiting viral dissemination and severity, and may also represent a generalizable mechanism exploited by other viral pathogens, highlighting the potential relevance of EV-mediated protein transfer beyond SARS-CoV-2.

overall_design: An IPF lung was dissociated and sorted into 4 populations based on the cell surface protein expressions of TMPRSS2 and EPCAM.

first: Lu

first: Remi

last: Klotz

first: Min

last: Yu


title: 4D force patterning enables spatial control of angiogenesis

status: Public on Mar 10 2026

city: Cambridge

first: Jessica

last: Shah

address: 77 Massachusetts Ave

institute: Massachusetts Institute of Technology

summary: Engineering organized microvascular networks remains a critical challenge in tissue engineering and regenerative medicine. While biochemical approaches for patterning angiogenesis via growth factor delivery have shown promise, their inability to pattern sustained growth factor gradients with precise spatiotemporal control limit their effectiveness. Here, we demonstrate that dynamically patterned mechanical forces can provide precise spatiotemporal control over angiogenic sprouting in 3D microvascular networks. We developed a magnetically actuated 3D human vessel-on-a-chip platform that integrates a perfusable endothelialized microchannel within a collagen matrix and allows non-invasive, tunable, multi-axial mechanical stimulation across all three spatial dimensions and time (4D). Using an automated 3-axis actuator, we systematically investigated how strain magnitude, frequency, and direction modulate endothelial cell behavior and vessel morphogenesis. Dynamic mechanical stimulation at physiological strain magnitudes (5–15%) enhanced endothelial alignment and barrier function while promoting angiogenesis in a strain-magnitude–dependent manner: lower dynamic strain (5%) maximized sprout initiation, whereas higher dynamic strain (15%) promoted elongation of individual sprouts. Sequential reorientation of strain direction further reprogrammed sprouting trajectories along X, Y, and Z directions, generating complex 3D microvascular geometries such as L-shaped branches. RNA sequencing revealed mechanically induced transcriptional profiles distinct from unstimulated controls, characterized by coordinated upregulation of angiogenic (VEGFA, FGFR1, PDGFA), mechanotransduction (ANKRD1, ZYX, FOSB), extracellular matrix remodeling (ABI3BP, SPOCK1, COL8A1), and barrier-associated (SERPINE2, P2RY1) genes and pathways. Functional perturbation of the mechanosensitive ion channel Piezo1 attenuated strain-induced sprouting without altering barrier stabilization, indicating that dynamic mechanical stimulation engages multiple mechanotransduction pathways to regulate angiogenic growth. Collectively, these findings establish a strategy for spatiotemporally controlled angiogenesis through engineered mechanical cues and demonstrate that 4D force patterning can program vascular morphogenesis while preserving function. This approach provides a foundation for engineering hierarchically organized vascular networks for tissue regeneration and disease modeling.

overall_design: HUVECs were cultured as 3D vessels in collagen-based extracellular matrix within a microfluidic “vessel-on-a-chip” device. After lumen formation and stabilization, devices were assigned to one of three mechanical conditions: (1) control (C), (2) 5% “low” strain (L), and (3) 15% “high” strain (H). Mechanical stimulation was applied using an external magnetic actuation system that deforms the surrounding matrix and vessel wall, thereby transmitting strain to the 3D endothelial vessel. At the end of the stimulation period, HUVECs were harvested from the 3D vessels for downstream profiling. Each RNA sample consisted of cells pooled from two independent devices under the same mechanical condition.

first: Sina

last: Kheiri

first: Ritu

last: Raman