title: Neutrophil extracellular traps aggravate COVID-19 related acute macular neuroretinopathy by promoting immune microthrombosis

city: Guiyang

first: jinbiao

last: lu

address: East Zhongshan Road

department: Department of Ophthalmology

institute: Guizhou Provincial People’s Hospital

summary: To observe retinal and peripheral blood bioinformatic characteristics of COVID-19 infected individuals with or without suffering acute macular neuroretinopathy (AMN)

overall_design: This case-control study enrolled patients who developed AMN following COVID-19 infection between December 2022 and January 2023. The control group consisted of individuals matching the patients in terms of sex, age, and disease duration who were infected with COVID-19 during the same period. Peripheral blood samples were collected for RNA-sequencing and ELISAs to explore bioinformatic characteristics

first: Xin

last: Liu

first: Hua

last: Li

first: Xiaoyan

last: Zhu


title: Ngn3 reprograms late retinal progenitor cells through transcriptional and epigenetic mechnisms [ATAC-Seq]

status: Public on Apr 24 2026

city: Guangzhou

first: SHUYI

last: CHEN

state: Guangdong

address: 54 S. Xianlie Rd

department: State Key Laboratory of Ophthalmology

country: China

institute: Zhongshan Ophthalmic Center, SYSU

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Ngn family transcription factors exhibit potent capacity to promote neurogenesis under diverse cellular context. Using in vivo electroporation on newbone mouse pups retinas, we demonstrate that overexpression of Ngn3 (Ngn3-OE) reprogramms the differentiation competent status of late retinal progenitor celle (RPC), promoting rod photoreceptor differentiation while repressing the fates of Müller glial cell and other interneurons. Herein, we perform RNA-seq and ATAC-seq to investigate the underlying molecular mechanism by which Ngn3 reprogramms late RPCs.

overall_design: Ngn3-overexpressing plasmids were introduced into late-stage RPCs via in vivo electroporation in postnatal day 1 (P1) mouse pups. Following electroporation, GFP-labeled electroporated late RPCs were isolated using fluorescence-activated cell sorting (FACS). Isolated cells were then processes for RNA-seq and ATAC-seq.

first: Shuyi

last: Chen


title: Bioinformatics analysis of BARX1 as a novel omental metastasis biomarker in high-grade serous ovarian cancer

city: Nanchang

first: Shaolin

last: Ma

address: No.17 Yongwai Street

institute: The first affilated Hospital of Nanchang University

type: Expression profiling by high throughput sequencing

summary: Omentum is one of the most preferred metastatic sites in patients with high-grade serous ovarian cancer, while the underlying mechanisms remain poorly understood. Here, we aim to identify biomarkers related to omental metastasis in high-grade serous ovarian cancer.  In this study,  we constructed a risk model comprising FAM9A, BARX1, SNORA79, CIDEA, FABP4, and TRARG1 as risk factors for omental metastasis using the machine-learning methods LASSO and Random Forest.  And we identified BARX1 (BarH-like homeobox 1) as the gene with the highest predictive value. Further studies validated the high expression of BARX1 across pan-cancers and its association with immune cell infiltration using CIBERSORT analysis. Our research underscores the crucial role of BARX1 in OC and highlights its potential as a therapeutic target.

overall_design: RNA-seq profiling of primary sites samples and omental metastasized samples of high-grade serous ovarain cancer

first: Wen

last: Hu


title: Gut microbiota-modulated glutamic acid rejuvenates the quality of oocytes deteriorated by advanced reproductive age [RNAseq-FMT]

city: Nanjing

first: Feixue

last: Wang

address: Xuanwu District

institute: Nanjing Agricultural University

summary: The gut microbiota plays a vital role in maintaining the physiological function of host health and the pathogenesis of various diseases. However, its relationship with maternal age-associated decline in oocyte quality remains elusive. Here, we report that establishment of gut microbiota from young donors in aged mice by fecal microbiota transplantation (FMT) is an effective method to rejuvenate the quality of maternally aged oocytes. Specifically, young gut microbiota promoted the ovulation and maturation of aged oocytes, and inhibited occurrence of cytoplasm fragmentation and spindle/chromosome abnormalities, hence enhancing the oocyte quality and female fertility. By integrating metagenome and untargeted metabolome of intestinal digesta, as well as targeted metabolome of ovaries and micro-transcriptome of oocytes, we identified that Bacteroides_caecimuris-modulated glutamic acid levels mediated the restorative effects of young gut microbiota on the aged oocytes through strengthening the mitochondria function. In addition, we demonstrated that in vivo supplementation of glutamic acid also enhanced the quality of aged oocytes, and the improvement of oocyte quality by glutamic acid was conserved across species. Altogether, our findings highlight the importance of gut microbiota in the oocyte aging and provide potential improvement strategies for age-related decline in oocyte quality and female fertility.

first: Wenjun

last: Zeng

first: Zihao

last: Zhang


title: VbdR target identification

status: Public on Apr 25 2026

city: Basel

first: Knut

last: Drescher

state: BS

address: Spitalstrasse 41

department: Biozentrum

country: Switzerland

institute: University of Basel

summary: In this study we determined the target spectra of the VbdR in biofilms via pulse-expression followed by RNA-sequencing.

overall_design: mRNA profiles of V.cholerae C6706 strain carrying pTac-ctr (empty vector control), pTac- vdbR (vc0142). The biofilms were grown in microfluidic chambers, after 21hr grown biofilms expression of the vdbR was induced by addition of 1mM IPTG, and RNA-samples were taken 1hr after induction. Three indepent biological replicates for each condition are provided.

first: Praveen

middle: K

last: Singh

first: Daniel

last: Rode

first: Kauzki

last: Nosho


title: The homozygous founder Psmb8 variant of Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome causes panniculitis-associated lipoatrophy and a shortened lifespan in mice

city: Suita

first: Daisuke

last: Motooka

state: Osaka

address: 3-1, Yamadaoka

country: Japan

institute: NGS core facility, Research Institute for Microbial Diseases, Osaka University

summary: Nakajo-Nishimura syndrome/proteasome-associated autoinflammatory syndrome (NNS/PRAAS) is a hereditary autoinflammatory disease. Clinically, NNS/PRAAS is characterized by periodic fever, skin rash, partial lipo-muscular atrophy, and joint contractures. Among PRAAS, NNS, is genetically characterized by a homozygous founder variant in the proteasome subunit beta type 8 (PSMB8) gene encoding an inducible proteasome component β5i. To establish an in vivo animal model recapitulating NNS/PRAAS , we generated mice harboring this founder variant. In Psmb8G201V/G201V mice, the immature β5i subunit was increased and 20S proteasome activity was significantly reduced in the spleen, whereas 26S proteasome activity was preserved and ubiquitin accumulation was not apparent. Compared with wild-type mice,　Psmb8G201V/G201V mice exhibited a shortened lifespan and, as they aged, showed less weight gain and adipocyte shrinkage with interstitial macrophage infiltration and cytokine production/activation. The mutant mice also manifested significantly lower proportion of T cells in total splenocytes, with higher CD4+ and lower CD8+ T cell proportions. Psmb8G201V/G201V mice shared some characteristic autoinflammatory and progeroid phenotypes as observed in NNS/PRAAS patients, although their proteasome defect pattern was distinct. Thus, Psmb8G201V/G201V mice should be useful not only for investigation of NNS/PRAAS pathogenesis but also for examining the clinical effect of candidate drugs on NNS/PRAAS and related diseases.

overall_design: comprehensive analysis of deregulated genes in B cells, T cells or Non-BT cells from Psmb8 +/+ or G201V/G201V mice

first: Tomoyuki

last: Hara

first: Akira

last: Kinoshita

first: Jun

last: Hamazaki

first: Hiroaki

last: Hemmi

first: Takashi

last: Kato

first: Izumi

last: Sasaki

first: Yutaka

last: Inaba

first: Yusuke

last: Yamashita

last: Okuzaki

first: Koh-Ichiro

last: Yoshiura

first: Shigeo

last: Murata

first: Masatoshi

last: Jinnin

first: Tsuneyasu

last: Kaisho

first: Nobuo

last: Kanazawa


title: Small molecule MBD2 pathway inhibitor KCC-07 suppresses breast cancer cell fitness

city: Montreal

first: Shafaat A.

last: Rabbani

state: QC

address: 1001 Bd Décarie

country: Canada

institute: McGill University

summary: Elevated expression of the DNA methylation reader methyl-CpG-binding domain protein 2 (MBD2) reprograms the transcriptional landscape of cancer cells to promote proliferation and invasion. Despite its emerging importance in cancer biology, pharmacological targeting of MBD2 to treat cancer is underexplored because of the presence of intrinsically disordered regions, which confound drug discovery. Here, we pharmacologically target MBD2 using KCC-07, a small-molecule inhibitor that blocks its DNA-binding ability, to evaluate its therapeutic potential in well-established in vitro and in vivo models of breast cancer. We found that KCC-07 administration caused a dose-dependent decrease in proliferative and clonogenic survival capabilities of mouse PyMT-R221A and E0771 breast cancer cells and substantially reduced their invasiveness in vitro. The anti-cancer effects of KCC-07 were further validated in vivo, where it markedly reduced the growth of orthotopic PyMT-R221A primary breast tumors in immunocompetent mice compared to the controls. In contrast, KCC-07 treatment neither prevented nor reduced lung colonization by PyMT-R221A cells in an experimental lung colonization model. Biochemical analyses of blood from KCC-07-treated mice showed no hepatotoxicity or nephrotoxicity. Transcriptomic analyses revealed that KCC-07 treatment upregulated the p53-associated gene expression program, which likely mediates its anti-cancer effects. Overall, our findings suggest that KCC-07, with its high selectivity, could be a promising therapeutic modality for treating primary tumors with elevated MBD2 expression.

overall_design: RNA-seq profiling of wildtype PYMT-R221A cells and KCC-07-treated PYMT-R221A cells as well as siMbd2-transfected PYMT-R221A and scramble siRNA control cells.

first: Niaz

last: Mahmood

first: Olivia

last: Dumas

first: Ani

last: Arakelian

first: Moshe

last: Szyf

first: Shafaat

middle: A


title: Co-targeting neurotransmitter signaling and CDK9 to treat diffuse midline glioma [CUT&RUN]

city: Houston

first: Rebecca

middle: Lauren

last: Murdaugh

state: Texas

address: One Baylor Plaza

department: Neurosurgery

country: USA

institute: Baylor College of Medicine

summary: Aberrant neurotransmitter signaling and transcriptional dysregulation are hallmarks of glioma and represent potential therapeutic targets. In this study, we uncover mechanisms of crosstalk between monoamine neurotransmitter signaling and transcriptional regulation in diffuse midline glioma (DMG) that can be co-targeted with CDK9 inhibitors (CDK9i) and neuropsychiatric drugs as a potential treatment strategy for DMG. We identified compounds that synergize with CDK9i in DMG using targeted drug screens, then assessed DMG response to CDK9i and neurotransmitter-targeting drugs in cell culture and in orthotopic xenograft mouse models. We then used a multi-omic approach combining proteomic, transcriptomic, and chromatin profiling with phospho-proteomics, RNA-seq, CUT&RUN, and ATAC-seq in DMG cells to characterize mechanisms of synergy between CDK9i and neuropsychiatric drugs. We observe differential expression of neuronal signaling genes in both CDK9i-resistant DMG xenograft tumors and CDK9-low pediatric high grade glioma patient tumors. Additional studies reveal that drugs that modify monoamine neurotransmitter signaling, including neurotransmitter reuptake inhibitors (SSRI/SNRI) and both metabotropic neurotransmitter receptor agonists and antagonists, strongly synergize with CDK9i to reduce DMG cell viability. Co-treating DMG with CDK9i+SSRI/SNRI triggered negative feedback inhibition of autocrine neurotransmitter receptor signaling and reversed a CAMKII-dependent mechanism of CDK9i resistance. Finally, we find that CDK9i+SSRI resulted in altered histone dopaminylation at neurodevelopmental genes associated with CDK9i-resistance. These findings identify neurotransmitter signaling pathways as novel points of vulnerability in CDK9i-resistant DMG that can be targeted with FDA-approved psychiatric drugs to modulate CAMKII signaling and histone dopaminylation in pediatric brain tumors.

overall_design: SU-DIPGXIII cells were treated for 24 hours with DMSO or 20 nM zotiraciclib + 5 𝛍M sertraline in biological duplicates, dissociated, washed, and used for CUT&RUN.

middle: L

first: Brittany

middle: R

last: Eberl

first: Rosemary

middle: U

last: Richard

first: Ena

middle: I

last: Campos-Hensley

first: Adanze

middle: N

last: Nnyagu

first: William

last: Elam

first: Nikko

last: Tsao

first: Ruiying

last: Ma

first: Jack

last: Tremblay

first: Alfred

last: Dei-Ampeh

first: Kieu

last: Pham

first: Daniel

middle: C

last: Kraushaar

first: Akdes

last: Serin-Harmanci

first: Kwanha

last: Yu

first: Calla

last: Olson

first: Benjamin

last: Deneen

first: Jamie

last: Anastas


title: Gene regulatory co-option drives birdsong neural circuit specialization [overexpression snRNA-Seq]

city: Santa Cruz

first: Bradley

last: Colquitt

state: CA

address: 1156 High St, Sinsheimer Labs 329

institute: University of California, Santa Cruz

summary: As animals evolve more complex motor skills, they acquire more diverse supporting motor circuits in their nervous systems. Yet the molecular mechanisms driving motor circuit evolution remain poorly understood. Birdsong, a learned complex motor skill with parallels to human speech, is controlled by a dedicated neural circuit -- the song system -- that is distinguished from nearby sensorimotor regions by molecular, physiological, and connectivity specializations. By profiling gene expression and chromatin accessibility in the songbird brain, we have found that each projection neuron type in the song system has a molecularly similar sister neuron type in adjacent non-song regions that lacks specialized gene expression and is transcriptionally similar to neurons in the chicken brain. The GRNs controlled by transcription factors \textit{MAFB} and \textit{EMX2}, typically active in fast-spiking interneurons and astrocytes, are specifically active in song-dedicated extratelencephalic projection neurons. Furthermore, the heterologous expression of \textit{MAFB} or \textit{EMX2} in chicken projection neurons was sufficient to drive song neuron-like expression programs. These results support a model in which song-dedicated neurons emerged from ancestral neural types in part through the co-option of GRNs active in other cellular contexts, providing a genetic mechanism underlying the evolution of birdsong.

overall_design: Several regions of the song system and comparator non-song regions were dissected from the brains of adult Bengalese finch (Lonchura striata domestica) males. The regions include, RA, HVC, and LMAN, and paired non-song regions, arcopallium, caudal nidopallium, and rostral nidopallium. Single-nucleus 3' RNA-seq libraries (10X Genomics) were prepared from these samples.

middle: M

first: Michael

middle: S

last: Brainard


title: Gut microbiota-modulated glutamic acid rejuvenates the quality of oocytes deteriorated by advanced reproductive age [FMT]

first: Feixue

last: Wang

overall_design: Bo,Xiong

first: Wenjun

last: Zeng

first: Zihao

last: Zhang


title: Co-targeting neurotransmitter signaling and CDK9 to treat diffuse midline glioma [ATAC-Seq]

first: Rebecca

last: Murdaugh

overall_design: SU-DIPGXIII cells were treated for 24 hours with DMSO or 20 nM zotiraciclib + 5 𝛍M sertraline in biological triplicates, dissociated, washed, and processed for bulk ATAC-seq (1 million cells/sample).

first: Brittany

last: Eberl

first: Rosemary

last: Richard

first: Ena

last: Campos-Hensley

first: Adanze

last: Nnyagu

first: William

last: Elam


title: A pivotal Wnt antagonist role promoting digit joint specification by constraining Wnt activity

city: Frederick

first: Susan

last: Mackem

state: MD

address: 1050 Boyles St. Building 560, Room 21-08

institute: NCI-Frederick

summary: Bmps and Wnts play opposing roles in several contexts during chondrogenesis and joint formation. Using genetic and genomic approaches, we found instead that canonical Wnts can cooperate with Bmps to enhance pSmad1/5 activity and initiate chondrogenic commitment in digit tip progenitors.   5’HoxdD/D mutant digits are characterized by elevated Bmp and pSmad1/5 activity and subsequent joint loss.  We show that expressing stabilized bcatenin (bcatCA) in interdigit mesenchyme rescues 5’HoxdD/D digit joint loss non-autonomously, by inducing secreted Wnt antagonists and normalizing digit tip pSmad1/5 levels. Indeed, genetic removal of Dkk2 in 5’HoxdD/D prevented joint rescue by bcatCA. Furthermore, elevating Wnt activity with Gsk3b antagonists in limb bud culture stabilized pSmad1/5 levels and enhanced Bmp activity.  Elevated pSmad1/5, as seen in 5’HoxdD/D, accelerates chondrogenic commitment, impeding a switch of phalanx forming region (PFR) cells in the digit tip to interzone (joint progenitor) fate.  We propose that, before progenitors transit into PFR, Wnt antagonists cooperate with Fgfs to prevent precocious pSmad1/5 accumulation by stabilizing Gsk3b to promote Smad-linker phosphorylation and Smad1/5 degradation.  Consequently, Wnt antagonists play a key role in modulating the pace of initial commitment of digit progenitors to chondrogenesis, together with Fgfs, and maintain mesenchymal plasticity to balance digit phalanx and joint formation.

overall_design: Comparison of RNAseq profiling between isolated interdigital tissues of control, 5'HoxdD/D and 5'HoxdD/D;bCatCA were used to look for the bCatCA target gene which can restore digit joint formatoin in 5'HoxdD/D.

first: Bau-Lin

last: Huang


title: Gut microbiota-modulated glutamic acid rejuvenates the quality of oocytes deteriorated by advanced reproductive age [Y-B]

overall_design: Intestinal contents were collected from young and aged mice to compare gut microbiome composition.

first: Bo

last: Xiong


title: Epithelial chemokine CCL25 integrates T cell development and intestinal homeostasis

city: Bethesda

last: Kelly

address: 41 Center Drive

department: Center for Cancer Research

institute: NCI

summary: The chemokine receptor CCR9 regulates thymic colonization of T-progenitors and intestinal accumulation of TCRgd+ intraepithelial cells (IELs). CCR9-ligand chemokine CCL25 is expressed predominantly in the thymus and the small intestine. By engineering tissue-specific CCL25-deficient mice, we demonstrate that CCL25 locally produced by thymic and intestinal epithelial cells individually supports developing T cell localization in the thymus and TCRgd+ IEL accumulation in the small intestine, respectively. More interestingly, our results reveal that thymic epithelial CCL25 facilitates T-cell positive selection in the thymic cortex. We further find that intestinal epithelial CCL25 promotes nutrient sensing in the small intestine. These results indicate that epithelial CCL25 directs thymic T-cell development and intestinal homeostasis in a tissue-specific paracrine manner.

overall_design: Single cells from dissociated thymus of wildtype mice and Ccl25 conditional knockout (Foxn1-Cre) mice were depleted for CD45+ hematopeotic cells and analyzed by scRNA-Seq to determine the cell-specific expression of Ccl25 and to examine the effect of knocking out Ccl25 on cell populations in the thymus.

first: Yousuke

last: Takahama

first: Jie

last: Li

first: Mei-Ting

last: Yang

first: Mami

last: Matsuda-Lennikov

first: Felix

last: Kalle-Youngoue

first: Aya

last: Ushio

first: Kenta

last: Kondo

first: Meleca

last: Gluckman

first: Kana

last: Bando

first: Takaya

last: Abe

first: Kensuke

last: Takada

first: Felipe

last: Martinez

first: Chuan

last: Wu


title: Global transcriptional changes across multiple isogenic C9orf72 Patient iPSC-derived neurons

city: Worcester

first: Alberto

last: Brusati

state: MA

address: N Lake Ave 55

department: Neurology

institute: UMass Chan Medical School

summary: Hexanucleotide repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD), yet the mechanisms underlying selective neuronal vulnerability remain unclear. A major challenge in identifying consistent transcriptomic changes across C9orf72 patient-derived lines has been due to heterogeneous differentiations, lack of isogenic controls and low sequencing depth. Here, we generated homogeneous cortical neurons (iCNs) from multiple isogenic C9orf72 patient iPSCs pairs and performed deep RNA sequencing. We identified robust and reproducible gene expression and splicing alterations in pathways related to cytoskeletal organization, extracellular matrix adhesion and synaptic signaling. Notably, we observed exon 30 skipping in FLNB, leading to the loss of its hinge domain. This was accompanied by altered FLNB localization, disrupted actin crosslinking and impaired mechano-transduction pathway. These findings reveal convergent transcriptomic and functional disruptions across multiple isogenic C9orf72 patient derived iCNs and offer new insights into ALS/FTD pathogenesis.

overall_design: RNA-seq was performed on i3 cortical neurons derived from multiple isogenic C9orf72 ALS patient iPSC pairs at Day15 of neuronal differentiation

first: Aparna

last: Sreeram

first: Desiree

last: Baron

first: Karly

last: Stallworth

first: Victoria

last: Doocy

first: John

middle: E

last: Landers


title: Gut microbiota-modulated glutamic acid rejuvenates the quality of oocytes deteriorated by advanced reproductive age

first: Feixue

last: Wang

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

relation:
SuperSeries of: GSE324538
SuperSeries of: GSE324539
SuperSeries of: GSE325001

overall_design: Refer to individual Series


title: Co-targeting neurotransmitter signaling and CDK9 to treat diffuse midline glioma [RNA-seq]

first: Rebecca

last: Murdaugh

overall_design: Tumor samples were isolated from xenograft NSG mice bearing SU-DIPGXIIIP*+ZsGreen/luciferase tumors treated for 3 weeks with vehicle or 15 mg/kg zotiraciclib 3 times per week by dissociating whole brains, depleting mouse cells, and using the human cell fraction for bulk RNA-seq. SU-DIPGXIII samples were treated in vitro for 24 hours with DMSO, 5 𝛍M sertraline, 20 nM zotiraciclib, 6 nM AZD4573, 20 nM zotiraciclib + 5 𝛍M sertraline, or 6 nM AZD4573 + 5 𝛍M sertraline in biological triplicates, dissociated, washed, and processed for bulk RNA-seq (250,000 cells/sample).

first: Brittany

last: Eberl

first: Rosemary

last: Richard

first: Ena

last: Campos-Hensley

first: Adanze

last: Nnyagu

first: William

last: Elam

first: Nikko

last: Tsao

first: Ruiying

last: Ma

first: Jack

last: Tremblay

first: Alfred

last: Dei-Ampeh

first: Kieu

last: Pham

first: Daniel

last: Kraushaar

first: Akdes

last: Serin-Harmanci

first: Kwanha

last: Yu

first: Calla

last: Olson

first: Benjamin

last: Deneen

first: Jamie

last: Anastas


title: Global knockout of melanoma differentiation-associated protein 5 protects mice from chronic hypoxia/SU5416-induced pulmonary hypertension

city: Columbus

first: Laszlo

last: Farkas

state: OH

address: 473 W 12th Avenue

institute: The Ohio State University

summary: Pulmonary arterial hypertension (PAH) is a severe disease affecting the pulmonary arteries, causing increased blood pressure due to narrowing of the pulmonary artery lumen. Aberrant proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs), along with a dysregulation of the immune response, contributes to arterial remodeling. We hypothesized that the cytosolic RNA receptor melanoma differentiation-associated protein 5 (MDA5) contributes to PAH by dysregulating pulmonary vascular cell function and immune cell response. In lung tissue from control patients and PAH patients, MDA5 immunoreactivity was widely distributed throughout the pulmonary artery wall. After exposing whole-body MDA5-/- mice to the chronic hypoxia/SU5416 (Hx/Su) protocol, we detected reduced right ventricular systolic pressure and pulmonary artery media wall thickness compared to wild-type mice. Pro-inflammatory mediators, interferon-regulated genes, and perivascular accumulation of CD11b+ myeloid cells were decreased in the lung tissue of Hx/Su-exposed MDA5-/- mice. In cultured human pulmonary artery ECs, MDA5 gene silencing disrupted DNA synthesis and angiogenic network formation. Bulk RNA sequencing analysis revealed the differential expression of 2,533 genes, affecting gene ontologies such as immune response, cell cycle, and cholesterol metabolism. Analysis of a publicly available single-cell RNA-sequence dataset indicates increased expression of MDA5 in monocytes/macrophages in pulmonary arteries from patients with PAH, which is associated with an interferon gene signature. Knockdown of MDA5 in macrophage-like cells reduced the type I interferon gene signature. Our data suggest a protective effect of whole-body MDA5 knockout in mice, which may be due to reduced immune dysregulation.

overall_design: primary pulmonary artery endothelial cells were transfected with siRNA targeting human MDA5 (IFIH1) or non-targeting control siRNA (IDT) at 50 nM  using GeneMute transfection reagent. After 16hours, the cell culture medium was changed, and mRNA was harvested 72h after transfection.

first: Dania

last: Abu-Saleh

first: Bryce

last: Piper


title: Archetype analysis of lung adenocarcinoma premalignancy links heterogeneity in premalignant lesions to diverging features of invasive disease

city: Boston

first: Adam

last: Gower

address: 72 East Concord Street, E632

department: Department of Medicine

institute: Boston University School of Medicine

summary: Lung adenocarcinoma (LUAD), the most common form of lung cancer, is a heterogeneous disease with highly variable histopathologic features and clinical outcomes. LUAD premalignant lesions (PMLs) are localized proliferative lesions of atypical pneumocytes that proliferate along the alveolar walls. In this study, we characterized the molecular heterogeneity across PMLs, regardless of histologic designation, and identified four unique groups or “archetypes” of PMLs using bulk RNA and exome sequencing data from laser captured microdissected PMLs, normal, and tumor tissue from LUAD resection cases. The archetypes were defined based on expression of recurrent gene co-expression modules discovered using the LUAD PMLs we profiled and three publicly available datasets. One PML archetype, termed “proliferation”, was associated with increased expression of genes involved in cell proliferation, a pro-tumor immune environment, and enrichment for EGFR driver mutations. Another archetype, termed “normal-like”, was associated with similar features to normal tissue, an anti-tumor immune response, and lacked enrichment for driver mutations compared to other archetypes. We projected the PML archetypes into independent gene expression datasets profiling LUAD and found that tumors closest to the proliferation archetype were enriched for multiple features of aggressive LUAD, including high tumor grade and lymph node invasion, and had significantly lower disease-free survival. Proliferation archetype PMLs may represent a subset of lesions with more aggressive features that could improve patient stratification and suggest novel targets for lung cancer interception.

overall_design:
Tissue blocks were obtained from a retrospective cohort of patients. RNA and DNA from multiple lesions (PML or tumor) and normal tissue were isolated from fixed tissue and subjected to bulk RNA sequencing.

***************************************************************
Data are being uploaded without FASTQ files to protect patient privacy.
***************************************************************

first: Kelley

last: Anderson

first: Linh

last: Tran

first: Kostyantyn

last: Krysan

first: Yohana

last: Kefella

first: Lingge

first: Gregory

last: Fishbein

first: Erika

last: Rodriguez

first: Maryam

last: Shabihkhani

middle: P

last: Stefanko

first: Emily

last: Green

first: Gang

last: Liu

first: Hanqiao

first: Sherry

last: Zhang

first: Erin

last: Kane

first: Mitra

last: Mehrad

first: Avrum

last: Spira

first: Steven

last: Dubinett

first: Eric

middle: J

last: Burks

first: Sarah

last: Mazzilli

first: Marc

last: Lenburg

first: Jennifer

last: Beane


title: Chromatin architecture reprogramming reveals novel epigenetic dependencies in breast cancer [ChIP-seq]

city: Miami

first: Rodrigo

last: Lucena Borges

state: Florida

address: 1501 NW 10th Avenue

department: Department of Human Genetics

institute: Sylvester Comprehensive Cancer Center

summary: Chromatin architecture plays a key role in development and cancer, yet most studies lack mechanistic depth due to widespread epigenomic remodeling. To address this, we tracked chromatin structure dynamics during the progression of endocrine resistance in ER+ breast cancer using Hi-C, chromatin accessibility, epigenomic, and transcriptomic profiling. We uncovered a critical role for H3K9 methylation and the demethylase KDM4C in driving proliferation of cells fated to become resistant through a non-genomic estrogen-mediated mechanism. These findings highlight the mechanistic contribution of chromatin regulation in therapy resistance and offer a blueprint for studying similar processes in cancer, development, and cell fate decisions.

overall_design: ChIP-seq of CTCF and Cohesin of T47D FM and Primed cells

first: Liliana

last: Garcia-Martinez

first: Mengsheng

last: Zha

last: Borges

first: Tong

first: Gretter

last: González-Blanco

first: Hao

last: Zhu

first: Zheng

last: Wang

first: Lluis

last: Morey


title: Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE) [dataset2]

city: La Jolla

first: Brian

last: Yee

address: 9500 Gilman Dr

department: Health

institute: UCSD

summary: RNA-binding proteins (RBPs) orchestrate post-transcriptional processes, including splicing, cleavage and polyadenylation, and translation. This dataset integrates enhanced CLIP (eCLIP) data for comprehensive characterization of RNA elements within human cells.

overall_design: Enhanced CLIP (eCLIP) experiments were performed for RNA-binding proteins in human K562 and HepG2 cells. Each experiment includes two biological replicates with corresponding size-matched input controls. eCLIP identifies protein-RNA interaction sites at high resolution by UV crosslinking, immunoprecipitation, and high-throughput sequencing.

first: Hsuan-lin

last: Her

first: Shuhao

last: Xu

first: Evan

last: Boyle

first: Katherine

last: Rothamel

first: Zia

middle: Z

last: Zhao

last: Blue

first: Eugene

middle: W

last: Yeo


title: Fragile nucleosomes are coupled with transcription activation of RNA Polymerase II [CUT&Tag]

city: Denver

first: Gongyi

last: Zhang

state: CO

address: 1400 Jackson St

department: Immunology and Genomic Medicine

institute: National Jewish Health

summary: Nucleosomes are barriers to RNA Polymerase II (Pol II) transcribing along gene bodies in eukaryotes. We found that a fragile “tailless nucleosome” could be generated to resolve the Pol II pausing caused by the +1 nucleosome in metazoans 1-4. We hypothesized that “pan-acetylated nucleosomes” along gene bodies are fragile and are generated to resolve the resistance of nucleosomes for the elongation of Pol II 5. To confirm this hypothesis, we systematically analyzed pan-acetylation and pan-phosphorylation of the entire human genome in HEK293T cells. Herein, we show that both pan-acetylation and pan-phosphorylation of histones in nucleosomes along gene bodies are coupled with the activities of Pol II. Our results show that there are four major types of fragile nucleosomes required for Pol II to transcribe along gene bodies: nucleosomes without tails, nucleosomes with dominant acetylation, nucleosomes with dominant phosphorylation, and nucleosomes with both acetylation and phosphorylation.

overall_design: We first carried out CUT&TAG-seq of H3K9ac, H4K12ac, H3S10ph, H4S1ph, Ser2ph-CTD of Pol II, and RNA-seq of HEK293T cells to check their distributions genome-wide. Then, we use an inhibitor DRB to shut down the transcription of the entire genome of HEK293T cells and carry out a PRO-seq analysis to check the time wise disapperance of newly syntheized RNAs. At the same time, we also carry  out CUT&TAG-seq of Ser2ph-CTD of Pol II,  H3K9ac, H4K12ac, H3S10ph, H4S1ph, with and without DRB to check the changes with time courses to confirm these histone modifictaions are coupled with the activites of Pol II.

first: Li

last: Lingbo

first: Hunter

last: Samuel

first: Leach

last: Sonia

first: Zhuang

last: Yonghua

first: Liu

last: Haolin

first: Gao

last: Junfeng

first: Zhang

last: Qianqian

first: Stasevich

last: Timothy

first: Kimura

last: Hiroshi

first: Dowell

last: Robin

last: Gongyi


title: Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE)

first: Brian

last: Yee


title: Chromatin architecture reprogramming reveals novel epigenetic dependencies in breast cancer [Hi-C]

first: Rodrigo

last: Lucena Borges

overall_design: Hi-C was used to probe the three-dimensional structure of the genome in Parental, Primed, Reprogrammed and ESR1:Y537S mutated cells

first: Liliana

last: Garcia-Martinez

first: Mengsheng

last: Zha

last: Borges

first: Tong

last: Liu

first: Gretter

last: González-Blanco

first: Hao

last: Zhu

first: Zheng

last: Wang

first: Lluis

last: Morey


title: Phenotypic profiling of neutrophils in acute Clostridioides difficile infection identifies a TNF-induced activation signature associated with epithelial damage.

city: Cincinnati

first: Rajat

last: Madan

address: 231 Albert Sabin Way

department: Infectious Disease

institute: University of Cincinnati

summary: We performed single-cell RNA sequencing (scRNA-seq) on enriched neutrophils isolated from murine bone marrow, blood, and colon. This study aimed to investigate neutrophil heterogeneity and plasticity in response to Clostridioides difficile infection (CDI) and to elucidate mechanisms of neutrophil-associated tissue damage.

overall_design: Mice were challenged with C. difficile M7404 spores following antibiotic-induced dysbiosis. Two days post-challenge, bone marrow, blood, and colon tissues were collected from the mouse exhibiting the highest clinical score. Bone marrow and blood samples from an uninfected (naïve) mouse were used as controls. Neutrophils were enriched using negative magnetic selection and processed by scRNA-seq.

first: Huber

last: Alexander

first: Madan

last: Rajat


title: Chromatin architecture reprogramming reveals novel epigenetic dependencies in breast cancer [Cut&Run]

overall_design: Cut&Run for T47D SiC/siKDM4C E2 and SiC/siKDM4C HD (H3K9me3, H3K27me3 and IgG for each condition)


title: Stress granule phase separation in stress-responsive cytosolic extract-in-oil droplets

city: Heidelberg

first: Alessia

last: Ruggieri

address: Im Neuenheimer Feld 344

department: Dpt. of Infectious Diseases, Molecular Virology

country: Germany

institute: Heidelberg University

summary: Stress granules (SGs) are biomolecular condensates that form transiently in the cytosol of mammalian cells in response to stress. Dysregulation of their assembly or disassembly is implicated in human age-related diseases. While phase separation is the key process underlying SG assembly, understanding of their function, composition and regulation in response to physiological stimuli is limited. This knowledge gap reflects the challenge of gaining comprehensive and quantitative insights into the dynamic regulation of the complex composition of SGs at the single-cell level. Here we present an emulsion-based microfluidics method to overcome this limitation. "Cytosolic extracts-in-oil droplets” (CEODs) recreate a confined active cytosolic milieu that undergoes phase separation and SG formation in response to stress under physiological conditions. This approach led to the discovery of six novel SG components involved in signalling pathways. CEODs provide a versatile and cost-effective screening platform for future mechanistic and therapeutic studies.

overall_design: RNAseq profiling of mock(untreated)-, dsRNA-, Silvestrol-, and PEG-induced condensates from U2OS cytosolic extracts compared to U2OS cytosolic input.

first: Aline

last: Reuter

first: Nathan

last: Mikhaylenko

first: Oskar

last: Staufer


title: Fragile nucleosomes are coupled with transcription activation of RNA Polymerase II [PRO-seq]

first: Gongyi

last: Zhang

first: Li

last: Lingbo

first: Hunter

last: Samuel

first: Leach

last: Sonia

first: Zhuang

last: Yonghua

first: Liu

last: Haolin

first: Gao

last: Junfeng

first: Zhang

last: Qianqian

first: Stasevich

last: Timothy

first: Kimura

last: Hiroshi

first: Dowell

last: Robin

last: Gongyi


title: eIF4G2-Mediated Translation Initiation of Histone Modifiers is Essential for Intestinal Stem Cell Maintenance and Differentiation

city: Wako

first: Shintaro

last: Iwasaki

state: Saitama

address: 2-1, Hirosawa

department: Center for Pioneering Research

institute: RIKEN

summary: eIF4G2 (also known as NAT1, p97, or DAP5) is an evolutionally conserved protein homologous to the C-terminal two-thirds portion of eukaryotic translation initiation factor (eIF) 4G. Despite its abundant and ubiquitous expression, the physiological and pathological functions of eIF4G2 are poorly understood. Here, we show that acute inactivation of eIF4G2 in adult mice results in rapid weight loss with abnormalities in multiple organs. Genome-wide ribosome profiling revealed that eIF4G2 is critical for the translation of key histone modification proteins involved in the maintenance and differentiation of intestinal stem cells. Our study underscores the importance of eIF4G2-mediated translation in multicellular organisms.

overall_design: Ribosome profiling and RNA-seq of small intestinal organoids from Eif4g2 KO mice

first: Haruko

last: Kunitomi

first: Aye

last: Khaine

first: Radia

last: Jamee

first: Maricelle

last: Lancerro

first: Eugenea

last: Rauchendeuri

first: Samuel

last: Perli

first: Yoshiko

last: Sato

first: Mio

first: Pedro

last: Ruivo

first: Kiichiro

last: Tomoda

first: Mari

last: Mito

first: Yuichi

last: Shichino

first: Shinya

last: Yamanaka


title: Fragile nucleosomes are coupled with transcription activation of RNA Polymerase II [RNA-seq]

first: Gongyi

last: Zhang

first: Li

last: Lingbo

first: Hunter

last: Samuel

first: Leach

last: Sonia

first: Zhuang

last: Yonghua

first: Liu

last: Haolin

first: Gao

last: Junfeng

first: Zhang

last: Qianqian

first: Stasevich

last: Timothy


title: Gene Regulatory Networks Orchestrating Oocyte Fate Bifurcation in Primordial Follicles Revealed by Single-Cell Transcriptomics

city: Nanjing

first: Xi

last: Wang

address: Longmian Avenue 101, Jiangning District

institute: Nanjing Medical University

summary: The first wave of primordial follicle activation occurs around postnatal day 2.5 (P2.5), with the remaining follicles entering a dormant state to ensure a continuous supply of fertilizable oocytes. However, the molecular mechanisms underlying this critical fate bifurcation remain poorly understood. Here, we employ SMART-seq2 to profile transcriptional dynamics in individual perinatal female mouse germ cells across three developmental stages: cysts at embryonic day 17.5 (E17.5), primordial follicles at P2.5, and primary follicles at P6.5. Unsupervised clustering and trajectory inference reveal two distinct transcriptional states in P2.5 oocytes, corresponding to dormant and activated subpopulations. Activated oocytes exhibit upregulation of genes linked to PI3K-Akt/mTORC1 signaling, extracellular matrix (ECM) disassembly, and oocyte maturation, whereas marker genes of dormant oocytes are enriched in oxidative stress response and DNA repair pathways. Transcriptional regulatory network reconstruction based on SCENIC inference identifies key transcription factors (e.g., Bhlhe41, Tcf3/12) orchestrating the fate bifurcation. Notably, dormant oocytes form a stable transcriptional state distinct from the continuous activation and development trajectory. Our findings provide a comprehensive landscape of gene expression and regulatory networks correlated to fate determination of P2.5 primordial follicles, paving the way for advanced therapeutic strategies for related diseases and improved techniques for in vitro follicle activation.

overall_design: We isolated mouse ovaries embryonic day 17.5 (E17.5), postnatal day 2.5 (P2.5), and postnatal day 6.5 (P6.5). The ovaries were enzymatically dissociated into single-cells suspensions, and individual germ cells were manually collected for single-cell RNA-sequencing (scRNA-seq).

first: Hanwen

first: Xingsi

last: He


title: Single-nucleus RNA-seq of mouse cortex following CCI-induced traumatic brain injury across multiple time points

first: Jiatong

last: Ji

address: 639 Longmian Avenue

institute: China Pharmaceutical University

summary: This dataset provides single-nucleus transcriptomic profiles of mouse cortex following controlled cortical impact (CCI)-induced traumatic brain injury (TBI) across multiple time points, including control, 6 hours, 2 days, and 4 days. It enables the investigation of dynamic, cell-type-specific transcriptional responses during injury progression, including immune activation, oligodendrocyte lineage changes, and neuronal responses. The dataset can be used to explore molecular mechanisms associated with brain edema and to facilitate cross-species comparisons with human TBI, helping to identify conserved and species-specific injury programs.

overall_design: A severe traumatic brain injury (STBI) model was established in 8-week-old C57BL/6 mice using a controlled cortical impact (CCI) approach. Cortical tissues were collected from control mice and at 6 hours, 2 days, and 4 days post-injury. Single nuclei were isolated from the cortex and processed for single-nucleus RNA sequencing using the 10x Genomics platform according to the manufacturer’s protocol. Three biological replicates were included for each condition.

first: Honglu

last: Chao

first: Enrico

last: Petretto

first: Jing


title: Flavonoid and isoflavonoid biosynthetic gene expression is affected by MYB36 transcription factor deficiency in Lotus japonicus [Salt_Experiment]

city: Sevilla

first: MARCO

last: BETTI

state: Sevilla

address: C. Prof. García González 1

department: Bioquímica Vegetal y Biología Molecular

country: Spain

institute: Universidad de Sevilla

summary: MYB36 has been identified as a new transcription factor (TF) that may be involved in isoflavonoid metabolism and stress responses in the model legume Lotus japonicus. A series of transcriptomic and metabolomic approaches have been carried out to attempt to identify the specific genes that can be under the control of MYB36 TF in this plant. For this purpose, transcriptomic data were obtained for wild type (WT) and two different lines of homozygous myb36 mutant plants, under two different stress conditions shown to be related with isoflavonoid metabolism: UV-B irradiation and salt stress. Results obtained showed a completely different and almost reciprocal picture of the global transcriptomic of the WT plants under both types of stress situations. Further comparison of up- and down- regulated genes revealed a very similar response of WT and mutant plants under UV-irradiation. In contrast, a completely different response was detected in salt stress between WT and mutant plants. None of the genes modulated by salt stress in myb36 mutants were also modulated by UV-B irradiation. Furthermore, most of the genes modulated by salt stress in the mutants corresponded to genes specifically involved in isoflavonoid but not flavonoid biosynthesis, thus illustrating on the genes that can be under the specific control of MYB36. These results identify for the first time MYB36 as specifical TF in the regulation of (iso)flavonoid biosynthesis, a class of compound specifically produced by legume plants. In addition, the results obtained revealed MYB36 as a crucial TF in the response to salt stress in legume plants.

overall_design: A comparative RNAseq analysis of WT and of Ljmyb36 mutant, KO for the LjMYB36 gene encoding for the MYB36 transcription factor was carried out. WT and mutant plants were subjected to a gradual increase of 50 mM NaCl every 4 days in the nutrient solution until reaching the final salt concentration of 100 mM NaCl, after which the plants were harvested (32 days of total growth and 2 days of growth in the presence of 100 mM NaCl). Control plants were watered with ‘Hornum’ nutrient solution for 34 days in absence of NaCl concentration. WT and mutant tissues were harvested after 4 hours of the beginning of the light period after 34 days of growth.

first: Maria Dolores

last: Monje-Rueda

first: Peter

last: Pal'ove-Balang

first: Antonio

last: Márquez

first: Marco

last: Betti

first: Margarita

last: García-Calderón


title: Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory circuits During Response to MAPK Inhibition in BRAF-mutant colorectal cancer.

first: Hey Min

last: Lee

state: TX

address: 1515 Holcombe Blvd

department: Gastrointestinal Medical Oncology

institute: University of Texas MD Anderson Cancer Center

summary: Background: Aberrant enhancer dynamics play a critical role in the initiation and progression of colorectal cancer (CRC). BRAFV600E-mutated metastatic CRC may be a unique subtype, exhibiting a strong epigenetic phenotype. Interestingly, bromodomain 2, a reader protein for H3K27ac-marked enhancers, was found to be synthetically lethal in CRC with BRAF + EGFR inhibition. Design: We evaluated the effectiveness of targeting aberrant enhancers with bromodomain and extraterminal (BET) + MAPK pathway inhibitors in patient-derived xenograft models of metastatic CRC, followed by comprehensive profiling of transcriptomic and chromatin dynamics upon BET inhibitor combination treatment. Results: The combination of BET and standard MAPK inhibitors has demonstrated improved efficacy against BRAFV600E CRC and selective improvements against RAS-mutant CRC in vivo.  We showed that BET + MAPK inhibition induced a profound downregulation of the MAPK signaling pathway compared to MAPK inhibition alone. The loss of activation signal on enhancers, as determined by H3K27ac, led to dysregulation of core-regulatory circuitries of CRC, especially loss of the auto-regulatory mechanism of the MAPK downstream E26 transformation–specific transcription factor family. Single nucleus multiome (RNA + ATAC) sequencing further distinguished differential transcriptomic and chromatin dynamics at cell type levels. Profound downregulation of well-differentiated cell types confirmed deep inhibition of MAPK signaling and downstream transcription factors. On the other hand, dedifferentiated cell populations were abundant after MAPK or combination inhibition, suggesting therapy-induced cell state switching and adaptation. Conclusion: We are evaluating BET + BRAF + EGFR inhibition in patients with treatment-refractory BRAFV600E metastatic CRC. ClinicalTrial.gov identifier: NCT06102902.

overall_design: To investigate the gene expression changes by iBET-151, binimetinib, and iBET-151 + binimetinib combination treatment in BRAFV600E mutant CRC PDX model. Mice were treated with vehicle (control) or short-term drug treatment (7 days).

first: Kunal

last: Rai

first: Scott

last: Kopetz


title: Neuronal microexons modulate arousal via the cAMP-PKA-CREB pathway in zebrafish

city: Barcelona

first: Tahnee

last: Mackensen

address: Dr. Aiguader, 88

institute: Universitat Pompeu Fabra

summary: Proper regulation of arousal maintains the balance of rest and activity and enables appropriate responses to stimuli; its disruption is a hallmark of many neurodevelopmental disorders. While transcriptional mechanisms of arousal control are well-defined, the contribution of post-transcriptional processes such as alternative splicing remains unclear. Here, we identify a critical role for the microexon splicing regulator srrm3 in maintaining arousal homeostasis in zebrafish. srrm3 mutants exhibit persistent hyperarousal characterized by sleep loss, sensory hypersensitivity, and elevated behavioural and neuronal activity. We identify the cAMP-PKA-CREB signaling axis as a central driver of mutant hyperarousal. Specifically, pharmacological inhibition of cAMP signalling rescues mutant hyperactivity and associated transcriptional changes while wild-type cAMP activation phenocopies the mutant. Downregulation of immediate early genes and a reduced CREB phosphorylation further suggest adaptation to sustained neuronal activation. These findings establish srrm3-dependent microexon splicing as a key molecular layer of arousal regulation linking RNA-processing defects to neuromodulatory imbalance.

overall_design: RNA-seq of FACS-sorted GFP⁺ neurons from 5 dpf Tg(elavl3:GFP) transgenic larvae with WT or srrm3∆eMIC backgrounds; 10x Genomics 3' (v3.1) scRNA-seq and ATAC-seq of FACS-sorted GFP⁺ neurons from 6 dpf Tg(elavl3:GFP) enucleated transgenic larvae with WT or srrm3∆eMIC backgrounds; RNA-seq of FACS-sorted GFP⁺ neurons from 6 dpf Tg(elavl3:GFP) enucleated transgenic larvae with WT or srrm3∆eMIC backgrounds either treated with DMSO (control) or ropinirole (ROP), clonidine (CLO), rolipram (ROL), forskolin (FSK), pentylenetetrazol (PTZ), SQ22536 (SQ); RNA-seq of FACS-sorted GFP⁺ neurons from 6 dpf Tg(elavl3:GFP) enucleated transgenic larvae with WT or srrm3^+/∆eMIC or srrm3^∆eMIC.

first: Luis

last: Pedro Iniguez

first: Thomas

last: Soares Mullen

first: Cristina

last: Rodríguez-Marin

first: François

last: Kroll

first: Giulia

last: Zuccarini

first: Jordi

last: Fernandez-Albert

first: Laia

last: Sancho-Vila

first: Jon

last: Permanyer

first: Isaac

last: Bianco

first: Michael

last: Orger

first: Jason

last: Rihel

first: Manuel

last: Irimia


title: A lineage shared core gene expression network specific to human infants, links human evolution to ASD in oligodendrocytes and Parkinsons disease in neurons

city: Rotterdam

first: Menno

last: Creyghton

address: Doctor Molewaterplein 40

country: Netherlands

institute: Erasmus MC

summary: Human-specific faculties of neural development at the postnatal stage are largely unknown, as evolutionary comparisons have either relied on adult material, immature cell culture proxies, or comparisons with more distant species. To address this, we performed snRNAseq (10x Genomics) on rare human, chimpanzee, and rhesus macaque prefrontal cortex (PFC) infant samples. This study represents the first to include infant chimpanzee samples in such evolutionary comparisons, providing novel insight into human-specific neural development and its susceptibility to neural disease.

overall_design: Frozen PFC samples were dissociated with tissue punches to include all cortical layers. Intact nuclei were sorted for DAPI+ nuclei to remove debris for 10x genomics snRNAseq.

first: Jonathan

last: Klavert


title: Chromatin architecture reprogramming reveals novel epigenetic dependencies in breast cancer [RNA-seq]

first: Rodrigo

last: Lucena Borges

first: Liliana

last: Garcia-Martinez

first: Mengsheng

last: Zha

last: Borges

first: Tong

last: Liu

first: Gretter

last: González-Blanco

first: Hao

last: Zhu

first: Zheng

last: Wang

first: Lluis

last: Morey


title: ATF2 phosphorylation is a core transcriptional driver of neuron apoptosis

first: Claire

last: LE PICHON

address: 35A Convent Drive, 2D933

department: NICHD

institute: National Institutes of Health

summary: Apoptotic neuron death is a common feature of many neurodegenerative diseases. Perhaps surprisingly, the exact mechanisms by which neurons undergo apoptosis have yet to be elucidated. We conducted an unbiased whole genome screen in human neurons to discover genes required for apoptotic neuron death and found the kinase MAP3K12 and transcription factors JUN and ATF2 among top hits. JUN is a known downstream target of the injury signaling cascade controlled by the MAP3K12 kinase (dual leucine zipper kinase or DLK), presumably via phosphorylation. Here, we show that JUN upregulation, but not its phosphorylation, is necessary for apoptosis, raising the question of how its upregulation is controlled. We demonstrate that phosphorylation of ATF2 by the kinases MAP3K12 and MAP3K13 is in fact the essential step for transcriptional upregulation of JUN. We identify phospho-ATF2 as the core driver of the pro-apoptotic transcriptional response in neurons and the factor responsible for converting the DLK/LZK kinase signaling cascade into a pro-degenerative transcriptional response. We validate this role of ATF2 in cultured human neurons and in injury models in vivo. Since targeting members of this signaling pathway to block neuronal death has proved difficult, ATF2 offers a promising alternative.

overall_design: 2 RNAseq experiments were performed. Experiment 1: 4 WTC11 iPSC cell lines (wild type, DLK KO, LZK KO and DLK LZK double KO) that each harbored a doxicycline cassette driving NGN2 expression were differentiated into cortical neurons. On day 14, cells were treated with 5 nM vincristine or DMSO vehicle for 16 hours, then RNA was harvested. Experiment 2: WTC11 i3Neurons expressing the CRISPRi machinery were transduced with lentivirus encoding gRNA against ATF2 or JUN, or a scrambled control gRNA. Cells were differentiated into i3Neurons and on day 14 were treated with DMSO or 5 nM vincristine, and RNA was harvested 16 hours later.

last: Le Pichon

first: Jorge

last: Gómez-Deza

first: Matthew

last: Nebiyou

first: Lara

last: El Touny

first: Mor

last: Alkaslasi

first: Zhenyu

last: Zuo

first: Josette

last: Wlaschin

first: Francisco

last: Nadal-Nicolas

first: Stacey

last: Slavutsky

first: Eliza

middle: Y

last: Lloyd

first: Nathan

last: Ashby

first: Mira

last: Sohn

first: Dale

last: Ryan

first: Wei

last: Li

first: Ken

last: Cheng

first: Pedro

last: Rocha


title: Chromatin Landscape Analysis of Patient PDAC

city: New York

first: Wilfred

last: Wong

state: NY

address: 430 E 67th St

institute: Memorial Sloan Kettering Cancer Center

summary: We established a human pluripotent stem cell (hPSC)-derived pancreatic progenitor organoid (PO) culture that provides the cellular plasticity for PDAC modeling and supports robust gene editing. Through the combinatorial expression of oncogenic KRAS and deletion of multiple tumor suppressor genes (TSGs)，we successfully recapitulated the transcriptional hallmarks of initial malignant transformation and progression of PDAC in POs in vitro. Moreover, these POs exhibited distinct histopathology from preneoplastic pancreatic intraepithelial neoplasia (PanIN) and moderately differentiated to poorly differentiated PDAC upon orthotopic transplantation. Further chromatin accessibility profiling unveiled 1) a progressive loss of pancreatic lineage program during disease development, accompanied by repression of TET1, 5hmc marking and hypermethylation of essential pancreatic lineage transcription factors and 2) an emergence of trans-lineage/malignant feature, associated with the opening of AP-1 motif enriched chromatin regions. Gene perturbation screening identified FOSL2, FOS, and JUNB as pro-malignancy AP-1 factors during malignant transformation of POs. Notably, inhibition of ERK, a regulator of AP-1, not only reversed AP-1 levels and malignant feature in transformed POs, but also derepressed TET1 and its associated chromatin regions. Thus, our de novo PDAC POs faithfully model the disease development and reveal distinct but concerted mechanisms that drive the cellular plasticity in PDAC. The comprehensive validation of this model against clinical datasets approves its potential for discovery of therapeutic targets and biomarkers for preventive screening in the future.

overall_design: Examination of nuclei from frozen sections of patient PDAC samples

first: Adrien

last: Grimont

first: Victoria

middle: G

last: Aveson

first: Rohit

last: Chandwani

first: Christina

last: Leslie

first: Steven

middle: D

last: Leach


title: Examination of DNA methylation in untransformed and transformed pancreatic progenitor organoids (POs) [EPIC Methyl Capture]

type: Methylation profiling by high throughput sequencing

overall_design: Examination of duplicates of PO samples using EPIC Methyl Capture

first: Xian

last: Zhang

first: Heng

last: Pan

first: Danwei

last: Huangfu


title: Comprehensive RNA-binding protein analyses using enhanced CLIP (ENCORE) [dataset1]

first: Brian

last: Yee

first: Hsuan-lin

last: Her

middle: A

first: Shuhao

last: Xu

first: Evan

last: Boyle

first: Katherine

last: Rothamel

first: Zia

last: Zhao

last: Blue

first: Eugene

last: Yeo


title: Transcription factor binding in early pancreatic progenitors (PP1)

last: Wong

overall_design: Examination of duplicates of early pancreatic progenitor using ChIP-seq

first: Dapeng

last: Yang


title: Low-input RNA-seq suggests metabolic specialization underlying morphological heterogeneity in a gut commensal bacterium

city: Wurzburg

first: Elise

last: Bornet

address: Josef-Schneider Strasse 2

institute: Helmholtz Insitute

summary: Isogenic bacteria can be phenotypically diverse. This heterogeneity is evident in the Bacteroidota, a predominant phylum of the human gut microbiota. These bacteria adopt diverse morphologies, yet the molecular basis of their morphological heterogeneity is poorly understood. Here, we systematically characterize the variation in cellular morphology of Bacteroides thetaiotaomicron cells during laboratory growth and after isolation from different host niches. We develop a sensitive transcriptomics approach and apply it to B. thetaiotaomicron sorted into sub-populations of varying cell sizes. Differential expression analysis indicates metabolic specialization associated with morphology. Transcriptomic data also reveal morphological marker genes, whose size-dependent expression is validated through fluorescence in situ hybridization. Morphological characterization of deletion and overexpression mutants reveals that specific marker genes causally contribute to B. thetaiotaomicron cell-size determination. Since phenotypic heterogeneity is a common feature of microbial consortia, this study serves as a blueprint for understanding the role of bacterial genes in morphological variation

overall_design: RNA-Seq profiling the different morphotypes of Bacteroides thetaiotaomicron

first: Gianluca

last: Prezza

first: Laura

last: Cecchino

last: Jenniches

first: Jochen

last: Behrends

first: Caroline

last: Tawk

first: Kerwyn Casey

last: Huang

first: Till

last: Strowig

first: Jorg

last: Vogel

first: Lars

last: Barquist

first: Antoine-Emmanuel

last: Saliba

first: Alexander

last: Westermann


title: AP-1 factor binding and histone status in transformed KCP pancreatic progenitor organoids (PO) [CUT&RUN]

first: Wilfred

overall_design: Examination of AP-1 factor binding and histone activation (H3K27Ac) in KCP POs by CUT&RUN

first: Xian

last: Zhang

first: Christina

last: Leslie

first: Danwei

last: Huangfu


title: Flavonoid and isoflavonoid biosynthetic gene expression is affected by MYB36 transcription factor deficiency in Lotus japonicus [UV-B_Experiment]

first: MARCO

last: BETTI

overall_design: A comparative RNAseq analysis of WT and of Ljmyb36 mutant, KO for the LjMYB36 gene encoding for the MYB36 transcription factor was carried out. WT and mutant plants were subjected to UV-B treatment for 16 h together with the continuous visible-light illumination. Control plants were subjected only with continuous visible-light illumination. WT and mutant tissues were harvested after 4 hours of the beginning of the light period after 30 days of growth.

first: Maria Dolores

last: Monje-Rueda

first: Peter

last: Pal'ove-Balang

first: Antonio

last: Márquez

first: Marco

last: Betti

first: Margarita

last: García-Calderón


title: Numb-Ifi204 inhibits microglial activation and the hippocampal inflammation induced by LPS.

city: Xi'an

first: Zhang

last: Siyu

state: ShanXi

address: GaoQiao

institute: Xi'an Jiaotong University

summary: This study aimed to identify the mechanisms regulating microglial activation and to explore potential therapeutic targets for neuroinflammation-related cognitive dysfunction disorders. We uncover a novel role for Numb in regulating microglial activation and highlight its interaction with Ifi204 in the LPS-induced TLR4 signaling pathway. We demonstrate that Numb promotes the autophagic degradation of Ifi204, thereby inhibiting the TLR4 signaling pathway and reducing excessive inflammatory responses in microglia. Furthermore, our findings show that Numb-mediated inhibition of microglial inflammation protects hippocampal neurons from synaptic damage, morphological abnormalities, and apoptosis.

overall_design: RNA-seq profilling of scr and shNumb cells


title: Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory circuits During Response to MAPK Inhibition in BRAF-mutant colorectal cancer

city: Houston

first: Hey Min

last: Lee

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP-seq) on bromodomain 2 (BRD2) and bromodomain (BRD4) in BRAFV600E-mutated CRC patient-derived xenograft (PDX) treated by either vehicle control, ZEN3694, encorafenib + cetuximab, or combination of ZEN3694 + encorafenib + cetuximab.

first: Kunal

last: Rai

first: Scott

last: Kopetz


title: tsRNAs sequencing of FFPE tissues reveals i-tRF-Gly-GCC as a biomarker for colorectal cancer

city: Guangzhou

first: Xiaoyun

last: Wang

address: 190 Kaiyuan Avenue, Huangpu

department: Infection and Immunity

institute: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

summary: Colorectal cancer (CRC) remains one of the most prevalent and deadly malignancies worldwide, requiring reliable biomarkers for detection. This study profiled tRNA-derived small RNAs in CRC tissues, identifying 1051 differentially expressed tsRNAs. Notably, i-tRF-Gly-GCC was significantly elevated in CRC tissues and patient sera compared to controls, with ROC analysis yielding an AUC > 0.7, underscoring its diagnostic potential. Weighted Gene Co-expression Network Analysis (WGCNA) revealed that i-tRF-Gly-GCC's target genes, including RAC2, which was downregulated in the COAD and READ datasets, are closely related to CRC. Gene Ontology and KEGG pathway analyses further linked i-tRF-Gly-GCC to cancer-related processes. Functional experiments in HCT-116 cells demonstrated that i-tRF-Gly-GCC enhances cell proliferation and migration. These results highlight i-tRF-Gly-GCC as a novel non-invasive biomarker for CRC detection and a potential therapeutic target, advancing our understanding of tsRNA-mediated regulation in CRC and paving the way for clinical applications.

overall_design: This study included 24 FFPE clinical tissue samples (12 CRC and 12 paracancerous) and 20 clinical serum samples (10 CRC and 10 healthy volunteers). High-throughput sequencing on tissue samples to construct colorectal cancer tsRNAs expression profiles. Use them to identify target genes of tsRNAs,and cellular experiments and analysis of TCGA datasets confirmed their role as biomarkers.

first: Yu

last: Wan

first: Yuting

last: Jiao

first: Anrui

last: Liu


title: PPARγ-Mediated Ferroptosis in Macrophages Enhances Persistent Pulmonary Infction by Mycobacterium tuberculosis

first: Zhiqiang

last: Huang

state: Jiangsu

address: Hankou 22

department: Medical School

institute: Nanjing University

summary: In this study, we found that Mycobacterium tuberculosis (Mtb) uses the PPARγ-GPX4 axis to induce ferroptosis in host cells, promoting persistent infection. Elevated PPARγ levels in macrophages post-Mtb infection, due to direct interactions with Mtb IDH and impaired degradation, lead to suppressed GPX4 expression and increased lipid peroxidation. Deleting PPARγ reduces lung inflammation, Mtb burden, and restores GPX4 expression in infected macrophages. This discovery of Mtb hijacking PPARγ to induce ferroptosis suggests a promising target for tuberculosis treatment.

overall_design: Multi-omics study investigates the epigenetic mechanisms underlying the interaction between Mycobacterium tuberculosis and macrophages, shedding light on the mechanisms of pathogen-host interactions.

first: Wenyuan

last: Pu

first: Hongwei


title: Integrating Epigenetics, Proteomics, and Metabolomics to Reveal the Involvement of Wnt/β-catenin Signaling Pathway in Oridonin-Induced Reproductive Toxicity

city: Fuzhou

first: Mengting

last: Chen

address: Fujian Medical University, 1 Xuefubei Road, Minhou, Fuzhou, Fujian province, China

institute: Fujian Medical University

summary: Oridonin is the primary active ingredient in traditional Chinese medicine Rabdosia rubescens, displaying various pharmacological activities such as anti-inflammatory, anti-tumor, and antibacterial effects. It is widely used in the clinical treatment of acute and chronic pharyngitis, tonsillitis, and bronchitis. Nevertheless, the reproductive toxicity of oridonin significantly restricts its clinical application, with the exact mechanism remaining unclear. This study aimed to investigate the mechanism of oridonin-induced damage to HTR-8/SVneo cells. By integrating epigenetics, proteomics, and metabolomics approaches, the mechanisms of oridonin-induced reproductive toxicity were discovered and confirmed through fluorescence imaging, RT-qPCR, and Western blotting. Experimental findings indicated that oridonin altered m6A levels, gene and protein expression levels, along with metabolite levels within the cells. Additionally, oridonin triggered oxidative stress and mitochondrial damage, leading to a notable decrease in WNT6, β-catenin, CLAUDIN-1, and ZO-1 protein levels. This implies that the inhibition of the Wnt/β-catenin pathway and disruption of tight junctions may be attributed to the cytotoxicity induced by oridonin and mitochondrial dysfunction, ultimately resulting in damage to HTR-8/SVneo cells.

overall_design: To investigate whether m6A modification is involved in reproductive toxicity following oridonin treatment, we performed MeRIP-seq on both oridonin-treated and control cells.

first: Qibin

last: Wu

first: Xinyue

last: Gao

first: Yifan

last: Lin

first: Caijin


title: Spatial transcriptomics identifies IL-32 as a lipid droplet-associated cytokine linked to tubular injury in human diabetic kidney disease [GeoMx]

status: Public on Apr 23 2026

city: Calgary

first: Justin

last: Chun

state: Alberta

address: 3330 Hospital Drive NW

institute: University of Calgary

summary: Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus and the leading cause of chronic kidney disease worldwide. Among the many drivers of tubular injury, lipid accumulation and inflammation are emerging as major contributors to kidney disease progression, but the molecular link between lipid metabolism and inflammatory signaling remains to be determined. Kidney biopsies from patients with DKD across pathologic classes were labelled for lipid droplets and analyzed by Nile Red spectroscopy. Digital spatial profiling and single-cell spatial transcriptomics were performed on samples from 14 patients representing different DKD classes. RNA scope and immunofluorescence microscopy were used for data validation and characterization. Lipid droplets (LD) were increasingly abundant in advanced stages of DKD, primarily accumulating in the proximal tubules. Single-cell spatial transcriptomics identified several genes—DUSP5, AZU1, COL9A1, HSPB1, and IGFBP7—as highly upregulated in DKD. Remarkably, IL32, which encodes a LD-associated cytokine, was highly enriched in injured proximal tubules. Immunofluorescence confirmed IL-32 localization to LDs predominantly within KIM1 positive tubules in moderate to advanced DKD. Furthermore, injured IL-32 expressing tubules were in close proximity to infiltrating neutrophils and macrophages, immune effectors of non-resolving inflammation and kidney disease progression. IL-32 is a LD-associated cytokine upregulated during tubular injury that represents a potential link between lipid dysregulation, inflammation and progression in human DKD.

overall_design: 5 um sectioned tissue samples from 2 FFPE transplant control pre-implantation biopsies and 3 DKD (class III) biopsies were prepared on slides. Nanostring GeoMx  Human Whole Transcriptome Atlas probes were hybridized to the tissue overnight. The fluorescent conjugated morphology markers used were CD10, PanCK, and SYTO 13 nucleic acid stain. Regions of interest were selected on the GeoMx Digital Spatial Profiler. RNA-ID and UMI-containing oligonucleotide tags were UV-cleaved from the WTA panel within the chosen ROIs and collected in a 96-well collection plate. Illumina i5 and i7 dual indexing primers were added to the oligonucleotide tags during PCR to index each ara of illumination uniquely.

first: Kieran

last: Meadows

first: Hyunjae

last: Chung

first: Son

last: Vo

first: Aysa

last: Imanzadeh

first: Heewon

last: Seo

first: Sisay

last: Belay

first: Asha

last: Swamy

first: Wulin

last: Teo

first: Kevin

last: Chapman

first: Graciela

last: Andonegui

first: Hallgrimur

last: Benediktsson

first: Peter

middle: K

last: Stys

first: Thang

last: Pham

first: Daniel

last: Muruve


title: Bulk RNA-seq of laser-microdissected granuloma and adjacent non-granuloma regions from FFPE lung tissues of pulmonary sarcoidosis

city: Sendai

first: Koji

last: Murakami

address: 1-1, Seiryo-machi. Aoba-ku

department: Respiratory Medicine

institute: Tohoku University Graduate School of Medicine

summary: Sarcoidosis is a systemic granulomatous disease with heterogeneous organ involvement and clinical outcomes. To characterize transcriptional features associated with pulmonary sarcoid granulomas, we performed bulk RNA sequencing of laser-microdissected granuloma regions and adjacent non-granuloma regions from formalin-fixed paraffin-embedded (FFPE) lung tissue specimens obtained from patients with pulmonary sarcoidosis. The dataset includes paired regional samples derived from clinically obtained lung specimens. These data provide a resource for investigating localized gene expression differences associated with granuloma formation in pulmonary sarcoidosis.

overall_design:
FFPE lung tissue specimens from patients with pulmonary sarcoidosis were sectioned and subjected to laser microdissection to isolate granuloma regions and adjacent non-granuloma regions. Bulk RNA sequencing was performed on paired samples from each specimen to compare regional transcriptomic profiles associated with sarcoid granuloma formation. The dataset contains seven paired granuloma and non-granuloma samples from human lung tissue.

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

last: Fujiwara

first: Tsutomu

last: Tamada


title: Episignatures associated with 8-week combined physical exercise in women with obesity

city: Divinopolis

first: Camila

middle: Fernanda Cunha

last: Brandao

state: Minas Gerais

address: Av. Paraná, 3001 - Jardim Belvedere I

department: Center for Chronic Non-Communicable Diseases of the Central-West Region of Minas Gerais

country: Brazil

institute: State University of Minas Gerais, Divinópolis, Brazil

summary: Aims: Obesity is influenced by epigenetic mechanisms; however, little is known about DNA methylation markers associated with exercise-induced health-promotion interventions. This aims to explore the episignatures of an 8-week combined physical exercise training protocol on DNA methylation patterns in women with obesity. Patients and Methods: Thirteen women with obesity (BMI: 33 ± 2 kg/m²; age: 34 ± 5 years) underwent assessments of body composition, waist circumference, physical performance (VO₂max), and peripheral blood collection before and after an 8-week combined physical training intervention (3 sessions/week, 55 minutes/session, 70-90% maximum heart rate). DNA methylation was analyzed using the Illumina EPIC BeadChip. Results: The intervention improved clinical outcomes, including reduced waist circumference and increased VO₂max (p < 0.05). Epigenome-wide analysis identified 15 differentially methylated regions, highlighting hypomethylation in SLFN11 and PM20D1 hypermethylation in GATA5. These genes are involved in pathways related to immune response, tumor suppression, thermogenesis, metabolic regulation, adiposity, glucose homeostasis, and transcriptional control. Conclusion: Combined physical training induced clinical improvements and DNA methylation changes in women with obesity, suggesting that exercise may alter the episignatures related to obesity.

overall_design: methylation


title: Nanoparticle-enabled tuning of cell density for enhanced adhesion and tissue repair

city: Suwon

first: Hyun Su

last: Park

address: 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do

country: South Korea

institute: Sungkyunkwan University

summary: Low retention of transplanted stem cells at target sites remains a major barrier to clinical translation. Conventional strategies — including genetic modification, chemical functionalization, and biomaterial encapsulation — often face limitations in translational feasibility, safety, or procedural complexity. Here, we present a nanoparticle-enabled biophysical approach to enhance cell retention. Cell-settling nanoparticles (CN), composed of clinically approved materials, are rapidly incorporated into mesenchymal stem cells (MSCs), increasing cellular density to accelerate gravitational settling and improve adhesion and survival. Building on this, we develop copper-chaperone-activatable nanoparticles (CCN), which enhance tissue regeneration and anti-fibrotic signaling through activation of fibroblast growth factor 2 (FGF2) and a positive feedback loop. In a mouse skin wound model, CCN-treated MSCs exhibit enhanced vascularization and reduced fibrosis. These findings demonstrate that modulation of cellular density and physical forces can improve stem cell engraftment, establishing a biophysical framework for safe and translationally relevant cell-based therapies.

overall_design: RNA-seq profiling of human ADSCs and ADSCs treated with nanoparticles (CN, CCN)

first: Gwang-Bum

last: Im

first: Joung Wook

last: Bae

first: Suk Ho

last: Bhang


title: The GET Pathway Modulates Azole Susceptibility through Sterol Metabolic Remodeling and Protein Trafficking in Filamentous Fungi

city: Beijing

first: Shuting

last: Ye

address: No.1 Beichen West Road, Chaoyang District,

institute: Institute of Microbiology, Chinese Academy of Sciences

summary: Azole antifungals are widely used to control fungal infection, yet resistance mechanisms beyond drug efflux and target modification remain insufficiently understood. Here, we identified the Guided Entry of Tail-anchored proteins (GET) pathway as a conserved regulator of azole susceptibility in Neurospora crassa and Aspergillus fumigatus. Deletion or dysfunction of the core GET components Get-3 or Get-4 confers resistance to multiple azoles without impairing hyphal growth or sporulation. Mechanistically, GET deficiency neither reduced intracellular accumulation nor altered drug efflux and target expression or total ergosterol levels. Instead, GET-deficient strains displayed significantly reduced accumulation of the toxic sterol intermediate 14α-methyl-3,6-diol under azole stress, indicating a potential bypass of azole-induced sterol toxicity. Proximity labeling and functional validation indicated that GET deficiency perturbs the trafficking of multiple azole-resistance-associated proteins, including the key tail-anchored protein transporter Emp-47 and mitochondrial Cox subunits Cox-4 and Cox-15, which deletion enhanced azole resistance. Transcriptomic and functional analysis further revealed that GET disruption altered the expression of some azole resistance-associated genes, which involve in membrane transport, metabolism, and cell wall organization, independent of canonical stress pathways. In this study, a total of 17 new genes that modulate azole susceptibility were identified. Collectively, our findings uncover a non-classical mechanism of azole resistance mediated by GET-dependent protein trafficking and metabolic adaptation, conserved across filamentous fungi.

overall_design: To thoroughly investigate mechanism of get-3 and get-4, we sequenced the transcriptome of get-3 and get-4 mutants treated with or without Ketoconazole.


title: Photosensitizer DTP Co-Administered with Statins Potentiates Renal Carcinoma Therapy by Modulating Cholesterol to Enhance PDT.

city: Tianjin

first: jianqiao

last: Li

address: No. 23 Pingjiang Road, Hexi District, Tianjin

institute: The Second Hospital of Tianjin Medical University

summary: Renal cell carcinoma (RCC) is the most common histological subtype of kidney cancer. Although targeted therapies and immune checkpoint inhibitors have markedly improved patient outcomes, their efficacy remains limited. In recent years, photodynamic therapy (PDT) has drawn increasing attention for its role in cancer treatment. To investigate the effects of the novel porphyrin-based photosensitizer meso-5-[ρ-DTPA-aminophenyl]-10,15,20 triphenylporphyrin (DTP) on RCC, we employed the human renal tubular epithelial cell line HK-2, human RCC cell lines 786-O, ACHN, and A498, as well as the murine renal carcinoma cell line Renca. We assessed intracellular DTP uptake, phototoxicity, and subcellular localization, and further explored potential mechanisms through next-generation sequencing. Our results showed that DTP uptake was significantly higher in RCC cells than in normal renal tubular epithelial cells, and DTP-PDT exerted pronounced phototoxic effects on RCC cells. Through sequencing and in vitro analyses, we found that DTP-PDT markedly reduced cholesterol levels in RCC cells while inducing compensatory upregulation of HMGCR. In vivo experiments further demonstrated that combining DTP-PDT with statins produced stronger anticancer effects. Overall, this study provides compelling evidence that DTP-PDT exhibits potent cytotoxic activity against renal cell carcinoma, and that statins can further enhance its therapeutic efficacy.

overall_design: RNA-seq profiling of 786-O renal cell carcinoma cells treated with DTP under photodynamic conditions (PDT) or dark conditions (Dark).

first: Jianqiao

first: Yuankang

last: Feng

first: Yong

last: Wang

first: Dan

last: Yue

first: Ge

last: Hong

first: Shiyue

last: Zhang

first: Shumin

last: Yu


title: Chromatin landscape analysis of pancreatic progenitor organoids (POs) bearing PDAC related mutations [ATAC]

first: Wilfred

last: Wong

overall_design: Examination of duplicates per genotype of POs in in vitro culture

first: Xian

first: Christina

last: Leslie

first: Danwei

last: Huangfu


title: The KMT2F histone methyltransferase interacts with the RNA polymerase I machinery to promote ribosomal RNA transcription.

city: Hyderabad

first: Shweta

last: Tyagi

state: Telangana

address: Opp. to Metro Rail Pillar No.NUP-9, Inner Ring Road, Uppal

country: India

institute: Centre for DNA Fingerprinting and Diagnostics (CDFD)

summary: Trimethylation of histone 3 lysine 4 (H3K4me3) is a mark of active transcription, and its regulatory role in RNA polymerase II-mediated transcription has been well-studied. However, if and how this mark regulates RNA polymerase I (RNA Pol I) is not known. Here, we used customized genome assemblies for rDNA to demonstrate that KMT2A and KMT2F bind to entire rDNA loci. The binding of these enzymes was mirrored by the binding of H3K4me2 and H3K4me3 marks. Using biochemical assays, we demonstrate the interaction of KMT2- specific subunits with RNA Pol I transcriptional machinery. Our findings reveal KMT2F as the primary KMT depositing the H3K4me3 on rDNA. Loss of H3K4me3 adversely affects the epigenetic landscape and leads to repression of the rDNA locus. Mechanistically, using mammalian cells as a model system, we demonstrate that KMT2F promotes the formation of the pre-initiation complex by RNA Pol I. Our findings highlight the thus far undiscovered role of H3K4me3 in the transcriptional initiation of rDNA genes.

overall_design: Chromatin immunoprecepitation DNA-sequencing (ChIP-seq) for KMT2A and KMT2F reported in this study as well as ChIP seq data analysed for RNA Pol I,UBF,H3k4ME2 and H3K4me3 reported from other studies in HEK293T cells

first: Kaisar

last: Lone

first: Amit

last: Karole

first: Geethanjali

last: Ravindran


title: Eosinophil-derived COX-2 protects against experimental colitis through the PGE2–IL-22 axis

first: Yang

last: Yang

address: 6432 Fannin St, MSB 6.261

department: Department of Anesthesiology, Critical Care and Pain Medicine

institute: University of Texas Health Science Center at Houston

summary: Inflammatory bowel disease (IBD) is driven by a breakdown in immune regulation and epithelial barrier function, yet the contribution of eosinophils to this process has remained poorly defined and controversial. While eosinophils infiltrate the intestinal mucosa during both flares and remission, their role in shaping disease outcomes is unclear. Our RNA-seq analyses of colonic eosinophils isolated from dextran sulfate sodium (DSS)-treated mice revealed a significant upregulation of cyclooxygenase (COX)-2 (gene name, Ptgs2). Eosinophil-specific deletion of COX-2 (Ptgs2fl/fleoCre+/−) reduced IL-22 production and exacerbated DSS- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, characterized by greater weight loss, higher disease activity, colon shortening, and epithelial injury. Administration of recombinant IL-22 reversed these phenotypes. Mechanistically, eosinophil-derived COX-2 enhanced IL-22 production by type 3 Innate lymphoid cells (ILC3s) through prostaglandin E2 (PGE2) signaling. Consistently, Ptgs2fl/fleoCre+/− mice exhibited reduced colonic PGE2 levels, while PGE2 analog treatment restored IL-22 production and mucosal protection. Our findings identify eosinophil-derived COX-2 and PGE2 as a critical regulator of IL-22 production during colitis, uncovering a eosinophil–ILC3 cross talk that safeguards the intestinal barrier and represents a promising therapeutic target in IBD.

overall_design: RNA-Seq profiling for colonic eosinophils isolated from water (control)- and DSS-treated C57Bl/6 WT mice

first: Cynthia

last: Ju


title: Transcriptome analysis of pancreatic progenitor organoids  (POs) carrying PDAC related mutations, treated with ERK inhibitors and depleted of AP-1 factors

overall_design: Triplicates of PO samples genetically modified and duplicates of PO samples treated with ERK inhibitors were examined.


title: Type I interferon signaling in microglia drives synaptic engulfment and neuronal loss following traumatic brain injury

city: Iowa City

first: Michael

last: Chimenti

state: Iowa

address: 431 Newton Road

institute: University of Iowa

summary: Type I interferon (IFN‑I) signaling has emerged as a central regulator of neuroinflammation across diverse central nervous system disorders, including traumatic brain injury (TBI). While TBI is a leading cause of neurologic morbidity and mortality through young adulthood, there is a paucity of neuroprotective therapies available to clinicians. Recent work has demonstrated neuroprotection after global IFN-I deficiency, yet the cell‑type‑specific contributions to traumatic brain injury (TBI) and the mechanisms of immune modulation remain poorly defined. Using mice with microglia‑specific IFN‑I receptor deficiency, we show that loss of microglial IFN‑I responsiveness suppresses microglial reactivity, reducing microglial accumulation, synaptic engulfment, antigen presentation, and T cell interactions after TBI. This attenuation preserves neuronal integrity and limits thalamic neuronal loss. However, despite this neuroprotection, microglia‑restricted IFN‑I blockade reveals functional redundancy across CNS cell types, underscoring the multi-cellular nature of IFN‑I signaling in the injured brain. Together, our findings delineate a microglial IFN‑I–dependent pathway that exacerbates secondary injury after TBI and highlight both the therapeutic potential and inherent limitations of cell‑type‑targeted IFN‑I modulation.

overall_design: RNA sequencing of microglia isolated from WTtg or microglial IFNAR KO mice 7 days after traumatic brain injury

first: Brittany

last: Todd

first: Zili

last: Luo

first: Molly

last: Larson

first: Polly

last: Ferguson

first: Alexander

last: Bassuk

first: Elizabeth

last: Newell


title: High-throughout sequencing of ovarian cancer cells treated with T-oligo

city: Wenzhou

first: Jiaying

last: Tong

address: Chashan Street

institute: Wenzhou Medical University

summary: After treating human ovarian cancer cells ES2 with T-oligo G4+RHPS4, high-throughput sequencing technology was employed. The transcriptome analysis revealed that T-oligo G4+RHPS4 does not exert its anti-tumor effect solely through telomere dysfunction, but instead simultaneously regulates cell cycle, senescence, and metabolic-related signaling pathways, thereby synergistically inducing the death of ovarian cancer cells.

overall_design: ES2 cells (3×10^5 cells per well, placed in 6-well plates) were treated with T-oligo G4+RHPS4 for 7 days. After the treatment, the cells were collected and total RNA was extracted from each group using TRIzol (TaKaRa Company, Japan). Finally, paired-end sequencing was performed on the Illumina HiSeq 4000 platform at LC-BIO Technology Company (Hangzhou, China).

first: Yeying

last: He

first: Xiaohui

last: Zheng


title: Bulk RNA sequencing in Mouse Bone Marrow-Derived Macrophages Following CD74 Deficiency

first: Tao

last: Gui

address: Huangpu Ave

institute: Jinan University

summary: Following CD74 knockout in mouse bone marrow-derived macrophages (BMDMs), we employed bulk RNA sequencing to systematically profile transcriptomic changes, with a particular focus on alterations in key regulatory elements. Building on these findings, we further investigated the potential molecular mechanisms through which CD74 modulates signaling pathways in macrophages, aiming to uncover its regulatory roles in immune responses and macrophage functional plasticity.

overall_design: This study employed bulk RNA sequencing (RNA-seq) on mouse bone marrow-derived macrophages (BMDMs) to comprehensively characterize the transcriptional landscape following CD74 deficiency. BMDMs were isolated from both CD74⁺/⁺ (wild-type) and CD74⁻/⁻ (knockout) mice, enabling a direct comparative analysis of gene expression profiles. By leveraging this unbiased, genome-wide approach, we aimed to identify differentially expressed genes and signaling pathways regulated by CD74, thereby providing molecular insights into the role of CD74 in macrophage biology and immune function.

first: Rui

last: Peng

first: Bo

last: Yu

first: Lutian

last: Yao

first: Lei

last: Zhang


title: Precision Editing of Cyclophilin A Generates Cyclosporine and Voclosporin Resistant Cellular Therapies

city: Boston

first: Rene

last: Bermea

address: 55 Fruit St

department: Pulmonary and Critical Care Medicine

institute: Massachusetts General Hospital

summary: Recipients of allogeneic transplants or patients with autoimmune disease require immune suppression, often with calcineurin inhibitors. There is an expanding repertoire of immune effector cell therapies, including CD19 CAR-T cells and viral-specific T cells, deployed in these patients; however, ongoing calcineurin inhibition may be detrimental to cell therapy function. We developed a CRISPR/Cas9-based approach to engineer dual cyclosporine/voclosporin resistant cell therapies by targeting PPIA (encoding cyclophilin A), a critical binding partner for both drugs. Because Cyclophilin A has homeostatic functions in T cells, a complete knock-out is detrimental to cell viability. We thus targeted its C-terminus, disrupting drug binding while leaving the majority of the protein intact. C-terminal editing was stable throughout expansion and preserved Cyclophilin A expression. Edited CD19 CAR-T cells retained effector function in the presence of cyclosporine and voclosporin, including proliferation, cytokine production, and target cell killing, resulting in improved survival in murine models of CD19+ leukemia. Edited CMV-specific T cells also demonstrated preserved antigen-specific proliferation and cytokine production in the presence of these drugs. C-terminal editing of Cyclophilin A offers a promising avenue for developing next-generation cell therapies for patients receiving calcineurin inhibitors.

overall_design: The submission includes bulk RNA-seq from human T cells that were CRISPR edited with a mock guide (negative control) or a guide that targets the last exon of PPIA. Cells were either re-stimulated or kept unstimulated and then magnetically separated into CD8 or CD4 fractions prior to bulk RNA-seq. Data reflect biological triplicates.

first: Holly

last: Wobma

first: Francesca

last: Calderon

first: Jiayi

last: Dong

first: Kayleigh

last: Omdahl

first: Xianliang

last: Rui

first: Elisa

last: Rojas Palato

first: Alexandre

last: Albanese

first: Franziska

last: Wachter

first: Marlana

last: Winschel

first: Katherine

last: Michaelis

first: William

last: Burns

first: Gillian

last: Selig

first: Lorenzo

last: Cagnin

first: Victor

last: Tkachev

first: Susan

last: Prockop

first: Peter

last: Nigrovic

first: Bruce

middle: R

last: Blazar

first: Ulrike

last: Gerdemann

first: Leslie

last: Kean


title: Ductal Epithelial MXD3 Promotes Disease Progression in Acute Pancreatitis through Wnt/b-catenin-Mediated Inflammation and Injury

city: Zhoukou

first: Xuejin

last: Liu

state: Henan

address: No. 26 East Renmin Road

department: Department of Gastroenterology

institute: Zhoukou Central Hospital Affiliated to Henan Medical University

summary: Acute pancreatitis (AP) is a severe inflammatory disease where epithelial injury and dysregulated repair are central to pathogenesis, yet the underlying transcriptional mechanisms remain poorly understood. This study employed an integrated approach to identify and characterize the transcription factor MXD3 as a master regulator of AP progression. Using single-cell RNA sequencing in a cerulein-induced rat AP model, we delineated a pathogenic epithelial trajectory from ciliated through non-ciliated to a proliferative state, with MXD3 emerging as the most significantly upregulated transcription factor in the proliferative cluster. Subsequent validation in pancreatic ductal epithelial-specific MXD3 knockout rats revealed profound protection against AP, manifesting as reduced histological damage, diminished fibrosis, attenuated neutrophil infiltration (MPO+ cells), and decreased expression of pro-inflammatory cytokines (IL-6, TNF-a, IL-1b). Mechanistically, we demonstrated that MXD3 directly activates the Wnt/b-catenin pathway, as evidenced by increased non-phospho b-catenin, its nuclear accumulation, and transcriptional upregulation of canonical targets (c-Myc, Cyclin D1, Axin2). Furthermore, functional rescue experiments confirmed the pathway's necessity, wherein the b-catenin inhibitor ICG-001 substantially reversed MXD3-driven apoptosis, necrosis, and pro-inflammatory cytokine secretion (IL-1b, IL-6, MCP-1) in vitro. Our findings establish a novel MXD3-Wnt/b-catenin axis as a crucial mechanism governing epithelial pathology in AP, revealing MXD3 as a promising therapeutic target for this debilitating condition.

relation:
Reanalysis of: GSM9464502
Reanalysis of: GSM9464503
Reanalysis of: GSM9464504
Reanalysis of: GSM9464505
Reanalysis of: GSM9464506
Reanalysis of: GSM9464507

overall_design:
We constructed a cerulein-induced acute pancreatitis (AP) model using wild-type mice, with 3 biological replicates in both the AP group and the saline-treated control group (n=3 per group).

***************************************************************
The table below lists GEO accessions reused/reanalyzed for this study.
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first: Xianru

last: Jia

first: Bingbing

last: Cui


title: In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells

city: Hong Kong

first: Yang

last: Fu

address: Prince of Wales Hospital, N.T, H.K, 32 Ngan Shing St, Sha Tin

department: Department of Orthopaedics and Traumatology

country: Hong Kong

institute: The Chinese University of Hong Kong

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

overall_design: Refer to individual Series


title: In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells [control]

summary: CRISPR/Cas9 has revolutionized genome editing with broad therapeutic applications, yet its repair patterns in vivo remain poorly understood. Here, we systematically profile CRISPR/Cas9 editing outcomes at 95 loci using our established CRISPR/Cas9/AAV9-sgRNA system in skeletal muscle stem cells (MuSCs). Through comprehensive characterization of the repair outcomes, our findings demonstrate that the general rules governing CRISPR/Cas9-mediated editing in vivo largely align with those observed in vitro. Additional to the anticipated small editing indels such as MMEJ mediated deletions and NHEJ mediated templated insertions, we uncover a prevalent occurrence of large on-target modifications, including large deletions (LDs) characterized by microhomology (MH) and large insertions (LIs). Notably, the LIs comprise not only exogenous AAV vector integrations but also endogenous genomic DNA fragments (Endo-LIs). Endo-LIs preferentially originate from active genomic regions, with their integration shaped by three-dimensional chromatin architecture. By disrupting key components of the NHEJ and MMEJ repair pathways in vivo, we identify their distinct roles in regulating the large on-target modifications. Together, our work systematically profiles the CRISPR/Cas9 repair outcomes in vivo and offers valuable guidance for improving the safety of CRISPR/Cas9-based gene therapies.

overall_design: Targeted deep sequencing was performed across three experimental cohorts: (i) 44 single-sgRNA and 51 dual-sgRNA target sites, along with their respective controls (notably, several single- and dual-sgRNA samples shared control data); (ii) one single-sgRNA and one dual-sgRNA target site evaluated across a multiple-dose treatment gradient; and (iii) enzyme knockout models versus control groups. Additionally, ATAC-seq and ChIP-seq assays were conducted to explore the chromatin features influencing indel formation.


title: Interleukin-34 induced Arg1+ macrophages play a key role in breast cancer brain metastasis

city: Durham

first: Wei

last: Yang

state: NC

address: 303 Research Drive

department: Anesthesiology

institute: Duke University Medical Center

summary: We use 10x Genomics to perform the visium RNA sequencing on two tumor tissue, which showed cell type clusters and whole genome profiling in each cell clusters. Visium CytAssist Spatial Gene Expression kit was used for FFPE (Mouse Transcriptome, 6.5 mm, 4 rxns, PN-1000521,10x Genomics).

overall_design: To study the tumorenvironment and  the cell types present in those breast cancer brain metastases, we generated spatial transcriptomics data from two biological replicates of the cerebellar BCBM generated from HP organoids.

first: Xiaoqing

last: Cheng

first: Khooshbu Kantibhai

last: Patel

first: Vaibhav

last: Jain

first: Simon

last: Gregory


title: Interleukin-34 induced Arg1+ macrophages play a key role in breast cancer brain metastasis.

summary: We use 10x Genomics to perform the Single cell RNA sequencing result shows cell type clusters and percentage of the corresponding cell types in the HP organoids that we used for our model.

overall_design: To further define the cell types present in these organoids, we performed single cell RNA-Seq (scRNA-Seq) on the HP organoids.

first: Maureen

last: Highkin


title: In vivo systematic detection of the outcomes of CRISPR/Cas9 mediated DNA repair in skeletal muscle stem cells [IDM-Seq long-read]