title: Profiling of gene expression, histone marks, chromatin accessibility, and DNA methylation in myeloid progenitors expressing H3WT, H3K4M, H3K27M, or H3K4M/K27M for 2 weeks [scRNA-seq]

first: Gracia

middle: M.

last: Bonilla

state: MA

address: 185 Cambridge St

department: Molecular Biology

institute: Massachusetts General Hospital

summary: Developmental gene expression is tightly regulated by the dynamic interplay of H3K4 and H3K27 methylation associated with active and repressed genes, respectively. However, our understanding of the individual and combinatorial roles these histone modifications play in a physiological context remains incomplete. Here, we have leveraged histone mutant transgenic tools to uncover a previously unappreciated role for H3K4 methylation in adult hematopoiesis. Adult mice globally depleted for all forms of H3K4 methylation via expression of an inducible histone H3 lysine-4-to-methionine (H3K4M) mutant allele succumbed to a severe loss of all major blood cell types. Unexpectedly however, H3K4M-expressing hematopoietic stem cells (HSCs) and committed progenitors were present at normal numbers and persisted long-term when transplanted into mice alongside unperturbed bone marrow, indicating that H3K4 methylation is dispensable for the maintenance and early commitment of HSCs but essential for the maturation of downstream progenitors. Importantly, the restoration of H3K4 methylation in H3K4M animals rescued their morbidity, released progenitors from the maturation block and enabled normal blood cell production. Mechanistically, we showed that H3K4 methylation opposes the deposition of repressive H3K27 methylation at differentiation-associated genes bivalently marked by H3K4me3 and H3K27me3 in HSCs or progenitors. Indeed, by concomitantly suppressing H3K27 methylation in H3K4 methylation-depleted mice we could rescue the acute lethality, hematopoietic failure and gene dysregulation. Collectively, our results reveal that H3K4 methylation safeguards hematopoiesis by opposing repressive H3K27 methylation at fate-instructive bivalent genes, providing evidence for the functional interaction between these crucial chromatin marks in mammalian tissue homeostasis.

overall_design: Single cell RNA-seq was performed for HSPCs (lineage-/cKit+/Sca1+) and MyPS (lineage-/cKit+/Sca1-) isolated from H3WT and H3K4M competitive chimeric mice after 2 weeks of doxycycline administration

first: Yagi

last: Masaki

first: Bonilla

last: Gracia

first: Sadreyev

last: Ruslan

first: Hochedlinger

last: Konrad


title: Gene expression profile at single cell level of primary and relapse mantle cell lymphoma (MCL)

status: Public on Jul 19 2025

city: Stockholm

first: Hui

last: Wan

address: Biomedicum, Solnavägen 9, floor 9D

country: Sweden

institute: Karolinska Institutet

type: Expression profiling by high throughput sequencing

summary: Mantle cell lymphoma (MCL) is a rare but often aggressive type of B-cell lymphoma with a high risk of relapse. To understand the mechanisms driving disease relapse, we employed single-cell RNA sequencing (scRNAseq) in 20 diagnosed/untreated (primary) and/or relapsed samples from 11 MCL patients.

overall_design:
scRNAseq was performed on 20 tumors from 11 MCL patients.

Submitter states: The raw scRNA-seq data generated in this study were deposited in the Swedish National Data Service (SND, accession DOI: https://doi.org/10.48723/kfy8-5r05). The data are not publicly available due to Swedish and EU data protection regulations and patient privacy concerns.

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

first: Weicheng

last: Ren

first: Qiang

last: Pan-Hammarström


title: Aberrant Transitional Alveolar Epithelial Cells Promote Pathogenic Activation of Lung Fibroblasts in Preclinical Fibrosis Modeling (Bulk RNA-Seq)

status: Public on Jul 25 2025

city: Philadelphia

first: Jeremy

last: Katzen

state: PA

address: 3450 Hamilton Walk, Stemmler Hall 216

country: USA

institute: University of Pennsylvania Perelman School of Medicine

summary: CD44+ and CD44- negative Alveolar type 2 cells (AT2) represent distinct populations in lung fibrosis. To charecterize these cells, we isolated CD44+/- AT2s from WT mice and from fibrotic Sftpc muant lungs and performd RNA sequencing no these populations

overall_design: To determine the transcriptional distinctions between CD44+ and CD44- alveolar type 2 (AT2) cells during fibrosis we isolated AT2 by FACS from lungs of control (n=4)  and Sftpc mutant lungs (n=4). Lungs were harvested from control and Sftpc mutant lungs, single cells suspension was prepared by mehcanical and enzymatic digetsion.  CD45+ and CD31+ cells were depleted using biotinylated antibodies followed by surface staining with antibody mix to identify CD44+ and CD44- AT2s. AT2 cells were identified as CD45-CD31-Epcam+CD104-CD200hi and then CD44+ or CD44-.

first: Evan

middle: T

last: Hoffman

first: Willy

last: Roque Barboza

first: Luis

middle: R

last: Rodriguez

first: Rachna

last: Dherwani

first: Kasey

last: Minakin

first: Yaniv

last: Tomer

first: Dakota

last: Jones

first: Aditi

last: Murthy

first: Adam

last: Bennett

first: Ana

last: Nottingham

first: Pushpinder

middle: S

last: Bawa

first: Feiya

last: Wang

first: Apoorva

last: Babu

first: Katrina

last: Chavez

first: Charlotte

middle: H

last: Cooper

first: Maria

middle: C

last: Basil

first: Micha

last: Brickman Raredon

first: Darrell

middle: N

last: Kotton

first: Konstantinos-Dionysios

last: Alysandratos


title: SRRM4 knockout helps the human mesenchymal stem cell line to intrude into decellularized bone

status: Public on Jul 16 2025

city: Tokyo

first: Iichiroh

last: Onishi

address: 1-5-45 Yushima, Bunkyo-ku

department: Pathology

country: Japan

institute: Institute of Science Tokyo

summary: Analysis of the human bone marrow microenvironment requires an in vivo model that reflects this microenvironment. We introduced a human bone marrow mesenchymal stem cell (MSC) line into decellularized bone. Using the CRISPR Knock Out library, we identified serine/arginine repetitive matrix 4 knockout in an MSC cell line, as a candidate factor for bone intruding, which may be applied to the analysis of hematological diseases such as myelodysplastic neoplasm.

overall_design: RNA-seq for Control UE7T-9 cell line(human mesenchymal stem cell line) and SRRM4 KO UE7T-9cell line. SRRM4 KO was induced using CRISPR.


title: Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [snRNA-seq]

status: Public on Jul 17 2025

city: St. Louis

first: Valeria

last: Cavalli

state: MO

address: 1 Bookings Dr.

institute: Washington University in St. Louis

summary: Peripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using single cell RNA sequencing, we show that satellite glial cells (SGCs), which completely envelop the sensory neuron soma residing in the dorsal root ganglia (DRG), express the endothelin B receptor (ETBR), while ET-1 is expressed by endothelial cells. Inhibition of ETBR ex-vivo in DRG explant cultures improves axon growth in both adult and aged conditions. In vivo, treatment with the FDA-approved compound, Bosentan, improves axon regeneration and reverses the age-dependent decrease in axonal regenerative capacity. Single-nuclei RNA sequencing and electron microscopy analyses reveal a decreased abundance of SGCs in aged mice compared to adult mice. Additionally, the decreased expression of connexin 43 (Cx43) in SGCs in aged mice after nerve injury is partially rescued by Bosentan treatment. These results reveal that inhibiting ETBR function enhances axon regeneration and rescues the age-dependent decrease in axonal regenerative capacity, providing a potential avenue for future therapies.

overall_design: L3, L4, and L5 DRGs from adult (2-3mo) and aged (12mo) WT (C57BL/6) mice. Following nucleus extraction, samples were analyzed using PIP-seq snRNA-seq.

first: Rui

last: Feng

first: Sarah

middle: F

last: Rosen

first: Irshad

last: Ansari

first: Sebastian

last: John

first: Michael

middle: B

last: Thomsen

first: Oshri

last: Avraham

first: Cedric

middle: G

last: Geoffroy


title: Profiling of gene expression, histone marks, chromatin accessibility, and DNA methylation in myeloid progenitors expressing H3WT, H3K4M, H3K27M, or H3K4M/K27M for 2 weeks [CUT&Tag]

city: Boston

first: Gracia

last: Bonilla

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: CUT&Tag sequencing was performed for H3WT, H3K4M, H3K27M, or H3K4M/K27M  samples in duplicate

first: Masaki

last: Yagi

first: Ruslan

last: Sadreyev

first: Konrad

last: Hochedlinger


title: KLF2 may suppress chicken adipogenesis by enhancing the GATA2 transcription

city: Shihezi

first: Zhiwei

last: Zhang

state: Xinjiang

address: A101-3,Xing 3 Building

department: Histology and Embryology

country: China

institute: Shihezi University

summary: Kruppel-like factor 2 (KLF2) acts as an essential modulator of adipogenesis; nevertheless, the exact molecular pathways governing its role remain uncharacterized. This investigation characterized the expression profile of KLF2 in human adipose tissue and elucidated the mechanisms by which KLF2 modulates adipogenesis in avian models. The KLF2 mRNA expression in human adipose tissues was substantial and exhibited significant heterogeneity influenced by gender and anatomical location, suggesting that KLF2 regulated adipose tissue functionality. In chicken preadipocytes ICP1, the KLF2 protein increased at the first 24 h of oleate-induced adipogenic differentiation and subsequently decreased over time. KLF2 facilitated the cellular proliferation of ICP1 cells (P<0.05). Moreover, KLF2 overexpression inhibited differentiation of chicken preadipocytes ICP1 (P<0.05). KLF2 also increased the density of mitochondria and mitochondrial cristae in ICP1 cells. RNA seq and luciferase reporter assays demonstrated that KLF2 suppressed the expression of genes in PPAR signaling pathway in ICP1 cells. Additionally, KLF2 interacted with the promoter region of chicken GATA2 and upregulated GATA2 transcription in ICP1 cells. In summary, KLF2 potentially influences the PPAR signaling cascade, mitochondrial bioenergetics, and GATA2 gene expression to enhance the proliferation of avian preadipocytes while inhibiting their differentiation.

overall_design: The ICP1 cells were inoculated into 6-well plates, and when the cells reached 60%-80% confluence, the given plasmids of pCMV-myc or pCMV-myc-KLF2 were transfected into the cells using ExFect® Transfection Reagent (#T101-02, Vazyme, Nanjing, China).After the transfection for 48 h, the ICP1 cells were harvested using TRIzol™ Reagent (#15596026, Invitrogen, Carlsbad, CA) for subsequent RNA sequencing.

first: Tingting

first: Qin

last: Gao

first: Yuechan

last: Chen


title: Profiling of gene expression, histone marks, chromatin accessibility, and DNA methylation in myeloid progenitors expressing H3WT, H3K4M, H3K27M, or H3K4M/K27M for 2 weeks [RNA-seq]

overall_design: RNA-seq was performed for H3WT, H3K4M, H3K27M, or H3K4M/K27M  samples in duplicate

first: Nikolaos

last: Tsopoulidis


title: Profiling of gene expression, histone marks, chromatin accessibility, and DNA methylation in myeloid progenitors expressing H3WT, H3K4M, H3K27M, or H3K4M/K27M for 2 weeks [RRBS]

type: Methylation profiling by high throughput sequencing

overall_design: Reduced representation bisulfite sequencing was performed for H3WT, H3K4M, H3K27M, or H3K4M/K27M  samples in duplicate

first: Chuck

last: Haggerty

first: Alexander

last: Meissner


title: Mitochondrial One-Carbon Metabolism is Required for TGF-β-Induced Glycine Synthesis and Collagen Protein Production

city: Chicago

first: Kun Woo

last: Shin

state: IL

address: 5841 S Maryland Ave

department: Medicine

institute: The University of Chicago

summary: A hallmark of Idiopathic Pulmonary Fibrosis is the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by lung fibroblasts requires de novo synthesis of glycine, the most abundant amino acid in collagen protein. TGF-β upregulates the expression of the enzymes of the de novo serine/glycine synthesis pathway in lung fibroblasts through mTORC1 and ATF4-dependent transcriptional programs. SHMT2, the final enzyme of the de novo serine/glycine synthesis pathway, transfers a one-carbon unit from serine to tetrahydrofolate (THF), producing glycine and 5,10-methylene-THF (meTHF). meTHF is converted back to THF in the mitochondrial one-carbon (1C) pathway through the sequential actions of MTHFD2 (which converts meTHF to 10-formyl-THF), and either MTHFD1L, which produces formate, or ALDH1L2, which produces CO2. It is unknown how the mitochondrial 1C pathway contributes to glycine biosynthesis or collagen protein production in fibroblasts, or fibrosis in vivo. Here, we demonstrate that TGF-β induces the expression of MTHFD2, MTHFD1L, and ALDH1L2 in human lung fibroblasts. MTHFD2 expression was required for TGF-β-induced cellular glycine accumulation and collagen protein production.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from Normal Human Lung Fibroblasts (HLFs) under TGF-beta treatment. MTHFD2 was inhibited by siRNA knock down.

first: Gokhan

last: Mutlu

first: Robert

last: Hamanaka

first: Rengul

last: Cetin-Atalay

first: Angelo

last: Meliton


title: Gene Expression in Human Rhabdomyosarcoma

city: Barcelona

first: Júlia

last: Perera-Bel

address: Doctor Aiguader, 88

department: MARData-BU

country: Spain

institute: Hospital del Mar Research Institute

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

overall_design: Refer to individual Series


title: Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [scRNA-seq]

first: Valeria

last: Cavalli

overall_design: L4 and L5 DRGs from adult WT (C57BL/6) mice were collected, dissociated into a single cell suspension, and analyzed using 10X Genomics scRNA-seq.

first: Rui

last: Feng

first: Sarah

last: Rosen

first: Irshad

last: Ansari

first: Sebastian

last: John

first: Michael

last: Thomsen

first: Oshri

last: Avraham

first: Cedric

last: Geoffroy


title: Profiling of gene expression, histone marks, chromatin accessibility, and DNA methylation in myeloid progenitors expressing H3WT, H3K4M, H3K27M, or H3K4M/K27M for 2 weeks [ATAC-seq]

first: Gracia

last: Bonilla

overall_design: ATAC-seq was performed for H3WT, H3K4M, H3K27M, or H3K4M/K27M  samples in duplicate

first: Masaki

last: Yagi

first: Ruslan

last: Sadreyev

first: Konrad

last: Hochedlinger


title: PRKG1 is a master regulator of the myogenic and malignant transcriptome of RMS cells.

summary: Silencing PRKG1 in RMS cell lines resulted in decreased tumor-forming capacity and enrichment of genes associated with muscle differentiation.

overall_design: The role of PRKG1 was investigated in PRKG1-depleted RMS cells using a transcriptomic approach.

first: Estela

last: Prada

first: Jaume

last: Mora

first: Inmaculada

last: Muñoz


title: Effect of LINE1 intervention on vascular calcification （RNA-seq）

status: Public on Jul 15 2025

city: Shenzhen

first: Ma

last: Jianshuai

address: No. 3025, Shennan Middle Road, Futian District

department: the Eighth Affiliated Hospital

institute: Sun Yat-sen University

summary: In this study, we report the protective effect of LINE1 intervention on vascular calcification. To elucidate the molecular mechanisms underlying the protective role of LINE1 inhibition, we employed RNA sequencing to identify gene expression changes under LINE1 suppression conditions. Our findings provide insights into the pathways involved in modulating vascular calcification and highlight LINE1 as a potential therapeutic target.

overall_design: Human vasculr smooth muscle cells  exposed to Pi for 7 days and transfected with si-scr or si-LINE1, or treated with NRTIs or not. RNA seq was employed to identify downstream targets of LINE1 inhibition in vascular calcification. Gene expression levels were calculated using the Fragment Per Kilobase of Million mapped reads, and differential expression was assessed using the DEGseq package.

first: Jianshuai

last: Ma

first: Dayu

last: He

first: Aoran

last: Huang

first: Ziting

last: Zhou


title: Transcriptomic analysis in 6 primary RMS tumors and their corresponding PDX.

first: Júlia

last: Perera-Bel

summary:
Gene expression analysis of Rhabdomyosarcoma patient biopsies and their Patient derived xenograft tissues. Transcriptimic and Functional analysis correlated with in vivo Ipatasertib efficacy.
PRKG1 mRNA levels in Rhabdomyosarcoma biopsies and PDX.

overall_design: Patient biopsy of pediatric rhabdomyosarcoma tumors and their corresponding subcutaneous patient derived xenograft were studied at trasncriptomic level using Human Genome U219 Array Plate (Thermo Fisher Scientific).


title: Protein arginine methyltransferase 7 regulates the cell cycle and promotes the progression of prostate cancer

status: Public on Jul 14 2025

city: Wuxi

first: Hongyuan

last: Wan

state: Jiangsu

address: Wuxi Medical College, Jiangnan University, Wuxi 214122, Jiangsu Province, China

summary: Background: Prostate cancer (PCa) is the second most common cancer in males worldwide. Arginine methyltransferase 7 (PRMT7) expression is associated with tumor proliferation, as it can drive tumor cell growth and promote its invasiveness in several types of cancer. However, its mechanism in PCa remains unknown. In this study, we investigated the function and related mechanism of PRMT7 in PCa cells. Method: The relationship between PRMT7 and PCa was analyzed using the TCGA online database. We used tissue chip techniques method to identify the clinical relevance of PRMT7 expression. PRMT7 expression levels in PCa tissues and cells were verified using RT-qPCR. Cell cycle, migration, proliferation, and apoptosis of PC3 and DU145 cells were observed using flow cytometry, CCK8, wound healing, plate cloning, and cell invasion assays. Gene set enrichment analysis and chip expression profiles were used to predict the potential signaling pathway involved in the action of PRMT7 in PCa. Results: First, TCGA, tissue microarray analysis, and RT-qPCR revealed that PRMT7 expression was increased in PCa tissues and cells. Furthermore, siRNA-mediated PRMT7 knockdown led to a significant reduction in the proliferation of cells, increased cell apoptosis, affected the cell cycle, and decreased cell migration and invasion. Additionally, PRMT7 regulated the functions of YY1, TP53, CCND2, CDK6, and RB1 in PCa. Conclusion: PRMT7 may promote proliferation, migration, and metastasis in PCa cells by regulating the activity of YY1,TP53,CCND2,CDK6, and RB1 in the cell cycle signaling pathway.

overall_design: RNA sequencing analysis was performed on PC3 cells with siPRMT7 and siCtrl knockdown.

first: Hangshen

first: Jiandong

last: Gui

first: Dongjie

last: Yang

first: Lijie

last: Zhu

first: Ninghan

last: Feng

first: Yuanyuan

last: Mi


title: Molecular Cartography of the Human and Mouse Down Syndrome Brain [MERFISH]

status: Public on Jul 11 2025

first: Brian

last: Kalish

address: 220 Longwood Ave

department: Neurobiology

institute: Boston Children's Hospital

summary:
Given the importance of linking human and model system pathobiology, we also performed highly multiplexed RNA in situ spatial transcriptomics on a well-established trisomic mouse model (Ts65Dn) to study the cellular landscape of the trisomic brain during early life and aging. We profiled the spatial transcriptome of > 240,000 cells in the mouse brain and identified trisomy-associated gene expression patterns in  the molecular control of neurogenesis, gliogenesis, and myelination.
Multiplexed error-robust fluorescence in situ hybridization (MERFISH) was performed on postnatal day 0 (P0) and 6 month (6mo) euploid and trisomic (Ts65Dn) mice (n=3 per condition). Coronal sections of the entire brain were used for analysis.

overall_design: Min Yi, Feng

first: Wuxinhao

last: Cao

first: Gen

last: Li

first: Bharti

last: Kukreja

first: Nareh

last: Tahmasian

first: Bianca

last: Rusu

first: Ji-Young

last: Youn


title: Molecular Cartography of the Human and Mouse Down Syndrome Brain [Slide-seq]

summary: To gain molecular insight into the prenatal neurobiology of DS, we performed single-nucleus sequencing, spatial transcriptomics, and proteomics on mid-gestational prenatal human brain tissue. We captured altered expression dynamics of lineage commitment genes in DS neural progenitor cells, which suggest changes to the fate and functionality of neuronal and glial cells.

overall_design: We performed Slide-seq on mid-gestational prenatal human samples (n=3 euploid, n=3 Down Syndrome).

first: Min Yi


title: Gene expression profiling of developing ovine embryonic fat tail tissues across nine stages (from E50 to E80) at single cell level

city: Dublin

first: Jiangang

last: Han

address: 59 Donnybrook Manor, Dublin 4

country: Ireland

institute: University College Dublin

summary: In mammals, whit adipose tissue (WAT) acts as the primary energy reservoir to modulate glucose and lipid homeostasis, and can also intervene several aspects of organismal physiology by endocrine manor. Hypertrophic development of WAT is associated with various metabolic disease, but hyperplastic adipogenesis is more responsible for metabolic health and distinct metabolic response across depots. However, our understating for cellular origins of adipocytes, the hierarchy of adipogenic progenitor population and the crucial regulons governing adipogenesis remains uncompleted. In this study, by constructing global gene expression and chromatin accessibility profiling for developing ovine fat tail tissue covering the whole stage of adipogenesis at single cell resolution, we identified several causal genes promoting adipogenesis and three cellular origins promising the congenital, repaid and massive fat deposition, including one progenitor and stem cell population (MCM5+/SFRP4+), two connective tissue progenitor clusters (COL6A6+/ALDH1A1+), and one vascular smooth muscle cell population (GUCY1B1+/RAI14+). Meanwhile, we also systemically investigated causal genes driving the dynamic specialization of angiogenesis, osteogenesis, chondrogenesis and myogenesis that accompanying fat tail development. Furthermore, by comprehensive integration of scRNA-seq and scATAC-seq data, we deciphered the enhancer-driver gene regulation networks (eGRNs) underpinning each lineage specialization in an unbiased manner. Collectively, our study broadens the understating for progenitor population hierarchy, enriches the available specific markers for various cell types, and provides new insights into cellular origins of adipocytes and molecular mechanism underpinning dynamic differentiation processes of multi lineages.

overall_design: The embryonic ovine tail tissues at E50, E55, E60, E63, E66, E69, E72, E75 and E80 were used to make single cell suspension and perform scRNA-seq, one replicate each time point. Sheep breed, Tan sheep, a kind of fat tailed sheep.

first: Lin

last: Jiang

first: Yuehui

last: Ma

first: David

last: MacHugh


title: Mouse embryo limb bud regeneration

city: Montpellier

first: Jholy

last: De la cruz

state: hérault

address: 80 avenue Augustin Fliche

country: France

institute: INSERM U1183

summary: Mouse embryos at the E10.5 stage display the ability to regenerate their limb buds, however this is quickly lost during embryogenesis . In the present study, we identified the E12.5 stage as the stage at which regeneration is lost. To deepen our understanding of the transcriptomic programs established during regeneration we generated microarray data from post-amputation tissues at E10.5 and E12.5 stages with a particular focus on early response to amputation observed at 1 and 3hpa. We believe this dataset will help understand how regeneration works in mammals as well as the key differences in a non-regenerative context.

overall_design: Microarray data was generated from 0,1 and 3 hours post-amputation for both E10.5 and E12.5 stages containing 3 biological replicates for each sample type.

first: Béryl

last: Laplace-Builhé

first: Gautier

last: Tejedor

first: Farida

last: Djouad


title: scRNAseq and TCRseq of tumor infiltrating CD8 T cells from samples

city: Shanghai

first: Feixiang

last: Wang

state: Shanghai

address: Chongqing South Road 280

institute: Shanghai Jiaotong University School of Medicine

summary:
The goal of this study is to investigate the role of ageing on tumor infiltrating CD8 T cells
Ageing is a major risk factor for various cancers, and patients aged 65 years or older represent up to 60% of newly diagnosed cancer patients. Ageing results in remodeling of T cell immunity, causing poor clinical outcomes in patients with cancer. During ageing, T cells undergo age-dependent changes and gradually lose their physiological function. Numerous studies have revealed that T cells mediate the surveillance and elimination of tumors, and substantial therapeutic strategies have been developed to improve tumor-specific T cell responses. However, these experimental studies were almost exclusively conducted in young but not old individuals. Therefore, how age-associated T cell dysfunction impacts antitumor immunity requires further investigation.

overall_design:
Fresh cancer patient tissues were collected and isolated into single cell for scRNAseq and TCRseq

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


title: LIGHT in Combination with IL-13 or IL-17 Drives Inflammatory Phenotypes in Human Pulmonary Fibroblasts

status: Public on Jul 10 2025

city: La Jolla

first: Jeamin

last: Jung

state: CA

address: 9420 Athena Cir

department: Bioinformatics Core

institute: La Jolla Institute for Immunology

summary: Fibroblasts are primary structural cells involved in tissue remodelling, but recent transcriptomic data have highlighted the ability of fibroblasts to display molecules that contribute to inflammation. Which factors might drive such inflammatory phenotypes are unclear. LIGHT (TNFSF14) is a cytokine that we previously showed was involved in inflammation of the lungs and may be central to lung diseases exhibiting fibrosis and inflammation, including asthma and interstitial lung disease. With RNA-seq, we investigated the activity of LIGHT in human pulmonary fibroblasts compared to IL-13 and IL-17, two other cytokines linked to lung disease. While all three cytokines individually induced both unique and overlapping gene transcripts, when fibroblasts were stimulated with LIGHT and IL-13 they upregulated more inflammatory transcripts including CCL2, CCL26, CXCL2, CXCL3, CXCL5, CXCL6, IL32, CSF2, VCAM1, ICAM1, IL18R1, IL1RL1, TNFRSF12A, TNFRSF4, TNFRSF8, ITGA2, ITGA4, and ITGAV; and when stimulated with LIGHT and IL-17, inflammatory transcripts included CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, IL32, IL33, CSF2, TSLP, IL1A, IL6, IL18, VCAM1, ICAM1, IL18R1, IL1RL1, TNFSF4, TNFRSF4, TNFRSF8, ITGA2, ITGA4, and ITGAV. Furthermore, multiple cell cycle-related transcripts were induced with the combinations of LIGHT with IL-13 or IL-17. Providing physiological significance, some of the fibroblast transcriptional signatures induced by these cytokines were found to be present in subsets of fibroblasts isolated from patients with interstitial lung disease. This study highlights the synergistic activities of LIGHT in lung fibroblasts and suggests it could drive inflammatory activities relevant for several diseases dependent on the availability of other classical cytokines made in the lungs.

overall_design: Bulk RNA seq. analysis from human pulmonary fibroblasts stimulated with 50 ng/ml LIGHT, 25 ng/ml IL-13, and 100 ng/ml IL-17A and in combination of IL13 or Il17A with LIGHT

first: Nandita

last: Ghosh

first: Rinkesh

middle: K

last: Gupta

first: Kai

last: Fung

first: Michael

last: Croft


title: Unanchored K63-linked polyubiquitin chains: a novel second messenger involved in G protein-coupled receptors early signaling events

status: Public on Jul 07 2025

city: Montreal

first: Marc

middle: J

last: Servant

state: Quebec

address: P.O. Box 6128, Downtown Station

department: Faculty of Pharmacy

country: Canada

institute: Université de Montréal

summary: GPCR rapidly transduced extracellular cues via their ability to activate effector proteins leading to the production of a variety of well-characterized second messenger molecules. We describe here that the E3 ubiquitin ligase tumor necrosis factor receptor associated factor 6 (TRAF6) is required for the rapid and transient production of unanchored lysine (K)63-linked polyubiquitin chains in primary and transformed cells exposed to vasoactive agonists Angiotensin II (Ang II), Lysophosphatidic acid (LPA) and Thrombin (Thr). We further show that unanchored K63-linked polyubiquitin chains accumulate in Transforming Growth Factor beta-activated kinase 1 (TAK1) and IkappaB kinase beta (IKKbeta) immunocomplexes and are required for the T-loop phosphorylation of TAK1 leading to IKKbeta, c- Jun N-terminal kinases (JNK1/2) and p38 mitogen-activated protein kinases (p38) phosphorylation and the induction of transcriptional events. Our results support a novel paradigm in field of GPCR signal transduction, identifying unanchored K63-linked polyubiquitin chains as novel second messenger molecules.

overall_design: RNASeq analysis conducted on HaCat cells stimulated with Lysophosphatidic acid (LPA). Production of stable HaCaT expressing FLAG 4x ZnF UBP : Platinum-A (Plat-A) retroviral packaging cell line (Cells BIOLABS) were transfected with the pMRX-ires-puro vector or with the pMRX-ires-puro Flag 4x ZnF UBP vector using Lipofectamine 3000 Transfection Reagent (Invitrogen) according to the manufacturer's instruction. The retroviral pseudoviruses were collected 48 hours after transfection and passed through a 0.45 µm filter. 1 600 000 HaCaT cells were infected with 2 ml of virus containing 10 mg/ml of polybrene for 48 hours and selected for 4 days with 1.5 µg/ml of puromycin, creating stable populations expressing either the pMRX-ires-puro vector or the pMRX-ires-puro Flag 4x ZnF UBP.  2) Stimulations: Serum-starved cells were stimulated with LPA (10 µM) for 15, 30 and 60 min or left untreated. RNA was extracted and submitted to RNASeq analysis

first: Priscilla

last: Doyon

first: Mohamad-Ali

last: El-Mortada

first: Jiunn

last: Roy

first: Firas

first: Florence

last: Dô

first: Simon-Pierre

last: Gravel


title: Molecular Cartography of the Human and Mouse Down Syndrome Brain [snRNA-seq]

first: Brian

last: Kalish

first: Min Yi

last: Feng

first: Wuxinhao

last: Cao

first: Gen

last: Li

first: Bharti

last: Kukreja

first: Nareh

last: Tahmasian

first: Bianca

last: Rusu

first: Ji-Young

last: Youn


title: ATAC-seq of  NCI-H358 cells treated with KRAS G12C inhibitor sotorasib

city: Nagoya

first: Hiromichi

last: Ebi

state: Aichi

address: 1-1, Kanokoden, Chikusa-ku

department: Division of Molecular Therapeutics

institute: Aichi Cancer Center Research Institute

summary: ATAC-seq of  sotorasib-resistant NCI-H358 cells treated with sotorasib

overall_design: NCI-H358 cells were treated with DMSO or 1uM sotorasib for 72 hour

first: Kentaro

last: Hirade

first: Takaomi

last: Sanda

first: Rui

last: Yamaguchi


title: Culturing of primary mouse hepatocytes is associated with major changes to the proteome and transcriptome

city: Copenhagen

first: Lars

middle: Roed

last: Ingerslev

address: Blegdamsvej 3B

department: NNF Center for Basic Metabolic Research

country: Denmark

institute: Copenhagen University

summary: Primary hepatocytes are a commonly used in vitro model for studying liver metabolism, but prolonged culturing results in dedifferentiation. Here we characterized the transcriptome and proteome of whole liver and primary hepatocytes as either freshly isolated cells or after 24 hours of 2D-culturing. We found that after 24 hours of 2D-culturing, hepatocytes showed differential expression of over  10,000 genes and 3,000 proteins compared to freshly isolated cells. This was accompanied by a reduced transcriptional heterogeneity and a loss of zonal markers. Cultures contained ~10% non-hepatocytes, including stellate- and dedifferentiated endothelial cells. Culturing also increased abundance of proteins associated with oxidative stress and inflammation, and changed mitochondrial, extracellular, and ribosomal protein abundance.  The data generated are available in the shiny-app “Hepamorphosis, https://cbmr-rmpp.shinyapps.io/hepamorphosis/”. Our finding show that primary mouse hepatocytes undergo significant changes in culture, limiting their utility for studying physiological and molecular mechanisms related to the liver.

overall_design: Single nuclei sequencing from liver biopsies (L), freshly isolated liver cells in suspension (CS), and primary hepatocytes following 24 hours of culture on collagen (PH)

first: Morten

last: Dall

first: Ben

last: Stocks

first: Daniel

last: Cervone

first: Atul

last: Deshmukh

first: Jonas

last: Treebak


title: Expression data from Rhabdomyosarcoma human cells treated with Ipatasertib or Miransertib.

first: Júlia

last: Perera-Bel

summary:
The AKT inhibitors Ipatasertib and Miransertib show differential anti-tumor activity against RMS.
We use microarrays to compare the transcriptomic effects of each AKT inhibitor in RMS and to identify the diffential gene signature of each drug in RMS.

overall_design: Rhabdomyosarcoma fusion positive cell line (RH4) was treated with vehicle (DMSO), Ipatasertib or Miransertib for 24h. The analysis of differential expressed genes was based on the comparison of RH4 cells treated (Ipatasertib or Miransertib)  versus vehicle (control) cells.

first: Estela

last: Prada

first: Jaume

last: Mora

first: Inmaculada

last: Muñoz


title: Enhancing CAR T Cell Therapy in Patients with Pancreatic Cancer

first: Gregory

last: Donahue

address: 3400 Civic Center Blvd, Bldg 421

department: Cell & Developmental Biology

institute: The University of Pennsylvania

summary: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a median survival time of less than a year, highlighting the urgent need for treatment advancements. We conducted a phase 1 clinical trial assessing the safety and feasibility of intravenous and local administration of anti-mesothelin CAR T cells in patients with unresectable or metastatic PDAC. Though therapy was well tolerated, limited clinical efficacy was observed. Analyses of patient samples provide insights into mechanisms of treatment resistance. Using single-cell genomic approaches, we found that CAR T cells post-infusion express exhaustion signatures, including previously identified transcription factors ID3 and SOX4, and display enrichment for Treg and GZMK+ phenotypes. Single knockout of ID3 or SOX4 appeared to enhance efficacy in xenograft models, but eventually failed, whereas double-knockout ID3 and SOX4 CAR T cells exhibit prolonged relapse-free survival, demonstrating sustained therapeutic effect and a potential avenue for engineering a more potent CAR T cell in pancreatic cancer.

overall_design: Examines gene expression by single-cell RNA-seq in T cells isolated from two patients undergoing a CAR T cell clinical trial, with isolation at 7 or 26 days post-CAR T infusion (isolation time not replicated); or tumor-infiltrating lymphocytes (TILs) extracted from three mice with recurrent tumors that had been treated with human CAR T cells, with two replicates subject to SOX4 knockout and one WT control.

first: M

middle: A

last: Aznar

first: Charly

last: Good

first: Julie

last: Barber-Rotenberg

first: Sangya

last: Agarwal

first: Wesley

last: Wilson

first: Alex

last: Watts

first: Zhen

last: Zhang

first: Donna

last: Gonzales

first: Greg

first: Wei-Ting

last: Hwang

first: Austin

last: Rennels

first: Andrew

last: Rech

first: Shunichiro

last: Kuramitsu

first: Karl

middle: M

last: Glastad

first: Katherine

last: Alexander

first: Gabriela

last: Plesa

first: Emily

last: Dowd

first: Andrea

last: Brennan

first: Donald

middle: L

last: Siegel

first: Janos

last: Tanyi

last: Haas

first: Drew

last: Torigian

last: Nadolski

first: Vanessa

middle: E

last: Gonzalez

first: Elizabeth

middle: O

last: Hexner

first: Joseph

last: Fraietta

last: Jadlowsky

first: Regina

last: Young

first: Shelley

last: Berger

first: Carl

last: June

first: Mark

last: O’Hara


title: KRAS G12C inhibition combined with CD47 and immune checkpoint blockage overcomes intrinsic resistance to concomitant KRAS G12C and immune checkpoint inhibitor therapy

first: Hiromichi

last: Ebi

summary: Although KRAS G12C inhibitors have altered the treatment strategy of patients with KRAS G12C mutant lung cancer, their efficacy is insufficient to eliminate tumors. Here, we identified that inhibition of mutant KRAS promotes escape from macrophage phagocytosis by upregulating the expression of ‘don’t eat me’ signal proteins, including CD47. CD47 was induced by the binding of FOXA1 to the super-enhancer of CD47. The addition of an anti-CD47 antibody restored macrophage phagocytosis and phenotype of macrophages.

overall_design: LLC Nras KO syngeneic lung tumors were treated with vehicle, sotorasib (100mg/kg), anti-CD47 (100μg/body), or the combination of these drugs at the same doses for 3 days. Tumors were harvested and subjected to spatial transcriptomics analyses.

first: Kentaro

last: Hirade

first: Noritaka

last: Tanaka

first: Rui

last: Yamaguchi


summary: THP-1 derived macrophage samples with phagocytosis and non-phagocytosis of tumor cells (duplicates for each condition).

overall_design: THP-1 derived M0 macrophages were co-culture with NCI-H358 for 24 hours and sorted into phagocytic macrophages and non-phagocytic macrophages.


title: Social isolation promotes hyperglycemia through sympathetic activation of inguinal white adipose tissue

status: Public on Jul 01 2025

first: Chao

last: Wu

state: 上海

address: 上海市普陀区真南路500号同济大学

institute: Tongji University

summary: Social isolation is a growing global public health concern, associated not only with mental health disorders but also with metabolic diseases such as type 2 diabetes.  This study investigates the molecular mechanisms by which chronic social isolation disrupts glucose homeostasis via sympathetic nervous system activation.  To elucidate adipose tissue transcriptional responses under socially isolated conditions, inguinal white adipose tissue (iWAT) was collected from male C57BL/6J mice subjected to either standard group housing or single housing for 8 weeks (n = 3 per group).  Bulk RNA sequencing was performed to characterize differential gene expression.  Analysis revealed substantial transcriptional reprogramming in iWAT from isolated mice, including upregulation of thermogenic and lipid metabolic pathways, such as Ucp1, and activation of key transcriptional regulators like Pparg.  These findings suggest that social isolation induces sympathetic-driven metabolic remodeling in adipose tissue.  The dataset provides valuable insight into how psychosocial stress influences peripheral metabolic gene networks and may contribute to stress-related metabolic disorders.

overall_design: Six 8-week-old C57BL/6J mice were evenly divided into two groups and raised separately or in groups, respectively, to simulate social isolation. After 8 weeks, the mice were euthanized, and subcutaneous fat from the inguinal region was collected for RNA-seq analysis.

first: Keran

last: Chen

first: Konglin

last: Huo


title: single-cell multiomics data for the developing human pelvic girdle [spatial]

status: Public on Jul 04 2025

city: Cambridge

first: Gayani

last: Senevirathne

address: 11 Divinity Avenue

department: Human Evolutionary Biology

institute: Harvard University

summary: Human pelvic girdle, especially the ilium is considered an evolutionary novelty. To understand the genetic architecute behind the formation of this structure, we conducted single cell multiomics across developmental stages.

overall_design: Fresh ilium samples were dissected out (along with the soft tissues surrounding them), flash frozen in OCT, and were processed using 10X Genomics visium spatial transcriptomics protocol. Each 10X genomics visium run has raw fatq files and input files

first: G


title: single-cell multiomics data for the developing human pelvic girdle [Multiomics]

overall_design: Fresh ilium samples were dissected out (along with the soft tissues surrounding them) and were processed using 10X Genomics multiomics protocol. Each 10X genomics multiomics run has raw fatq files for RNA and ATAC, along with the same processed files.


title: Coinfection with Fowl Adenovirus Serotypes 1 and 4 (FAdV-1 and -4) Enhances FAdV-4 Replication through FAdV-1-mediated Upregulation of HSPA2 Expression

status: Public on Jul 12 2025

city: Yangling

first: xiaoxuan

last: Li

state: ShaanXi

address: 3 Taicheng Street

institute: Northwest A & F University

summary: Fowl adenoviruses (FAdVs) are widely distributed in poultry populations around the world, and many diseases are associated with FAdV infection in chickens. This study documented the first characterization of coinfection with fowl adenovirus serotypes 1 and 4 (FAdV-1 and -4) associated with hydropericardium hepatitis syndrome (HHS) in Chinese layer flocks, revealing a novel viral cooperation mechanism. Two novel strains (CH/SX/201805-1 and -4) were identified and isolated, with whole-genome sequencing showing CH/SX/201805-1 clustering with FAdV-1 (99.7% identity to FAdV-A-61/11z), whereas CH/SX/201805-4 displayed characteristic ORF19/27/29 deletions mirroring emergent Chinese FAdV-4 variants. Experimental coinfection in SPF chickens resulted in 87.5% mortality, which was 16.7% greater than that resulting from infection alone, with exacerbated pathology. In vitro coinfection experiments demonstrated concurrent viral replication within same LMH cells, a previously unreported phenomenon, where FAdV-1 increased FAdV-4 replication efficiency 21-fold (P<0.001). Transcriptomic profiling revealed heat shock protein A2 (HSPA2) as the most differentially expressed gene, which was upregulated 2.8-fold during coinfection compared with infection with FAdV-4 alone. Functional validation through HSPA2 knockdown reduced FAdV-4 replication, establishing that FAdV-1 potentiates FAdV-4 through HSPA2-mediated host modulation. These findings provide the first evidence of HSPA2-dependent interserotype synergy in avian adenoviruses and can be used to develop a cellular model for FAdV coinfection studies. These insights redefine the understanding of FAdV pathogenesis and create new avenues for targeted intervention strategies against emerging poultry adenoviral coinfections.

overall_design: LMH cells were seeded in 6-well plates and divided into four groups: the FAdV-1 alone group, the FAdV-4 alone group, the coinfection group and the control group. The cells were inoculated with CH/SX/201805-1 (MOI = 1), CH/SX/201805-4 (MOI = 1), or a mixture of both (MOI = 0.5 each). At 12 hpi, total RNA was extracted via TRIzol (TaKaRa, Tokyo, Japan) and sequenced via a NovaSeq 6000 sequencer (Illumina Inc., San Diego, CA) by Beijing Biotechnology Company Ltd. (Beijing, China). The raw reads were processed via fastp (https://github.com/OpenGene/fastp), and the sequences were mapped to the Gallus gallus genome (NCBI GCF_000002315.6) via HISAT2.2.4. DEGs were identified via edge R with a log2 (fold change) ≥ 1 and P < 0.05.

first: Miao

last: Dan

first: Dongying

last: Liu

first: Binbin

last: Ren

first: Yifan

last: Ge

first: Yayu

first: Julian. A

last: Hiscox

first: James P.

last: Stewart

first: Qin

last: Zhao

first: Mingzhi

last: Liao

first: Yani

last: Sun


title: Resuscitation from Near Cell Death Unleashes Developmental Cues that Enhance Tissue Repair and Regeneration

city: Hyderabad

first: Nitesh

middle: Kumar

last: Singh

state: Telangana

address: Habsiguda

department: Bioinformatics

country: India

institute: Center for Cellular and Molecular Biology

summary: Resuscitation from near-cell death conditions is an intriguing but not well-understood cell biology phenomenon. First, we conclusively demonstrate that cells could revive from the early cell death phase evoked by LLOMe and other lysosomotropic agents. The resuscitation phase was found to be a highly orchestrated cellular and molecular process, where the fragmented cell organelles of the death phase fully renewed themselves within a few hours. Remarkably, the initiation of the resuscitation phase was accompanied by the upregulation of pathways of embryonic development, tissue repair, regeneration, and stemness. This was followed by the induction of networks of genes of vital cellular and metabolic pathways. Prompted by in vitro results, we tested whether LLOMe could affect tissue repair, regeneration, and stemness in vivo. Indeed, LLOMe dramatically induced repair in skin wound and corneal alkali burns mouse models. Also, it stimulated the production of hematopoietic stem/progenitor cells in the Drosophila melanogaster, enhanced tadpole tail regeneration in the frog, and promoted axon regeneration in the Caenorhabditis elegans. Fascinatingly, LLOMe treatment of frog tadpoles resulted in accelerated developmental growth. Among others, NF-ĸB signaling was found to be most critical for the revival of cells as well as the regeneration process. Thus, for the first time, we demonstrate that resuscitation from near-cell death conditions is an elegantly programmed process and that this process could be harnessed for therapeutic advances in regenerative medicine.

overall_design: Distribution of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) using Oxford Nanopore sequencing with DNA isolated from control and LLOMe treated MEF cells (30mins, 3hours and 24hours).

first: Kollori

last: Dhar

first: Kautilya

last: Jena

first: Reuben

last: Mathew

first: Soumya

last: Kundu

first: Divya

middle: T

last: Sowpati

first: Santosh

last: Chauhan


title: Chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage

city: Birmingham

first: Wioletta

last: Czaja

state: AL

address: 1918 University Blvd

department: Department of Genetics

institute: University of Alabama at Birmingham

summary: The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair, and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.

overall_design: RNA-seq profiling of wildtype HAP1 cells (C631) and their HELLS KO derivative.

first: Arko

last: Sen


title: The mosquito transcriptome is shaped by the individual and interactive effects of warmer temperature and aging

city: Nashville

first: Julian

last: Hillyer

state: TN

address: VU Station B, 35-1634

department: Department of Biological Sciences

institute: Vanderbilt University

summary: In mosquitoes, warmer temperature accelerates the progression of senescence, weakening their ability to survive and respond to an infection. Thus, we hypothesized that this phenomenon is driven by changes in gene expression. To test this hypothesis, we employed an RNA-sequencing approach to investigate how warmer temperature and aging, individually and interactively, shape the transcriptome of the female African malaria mosquito, Anopheles gambiae. Warmer temperature increases the expression of genes involved in metabolism and cell signaling but decreases the expression of genes involved in replication, transcription, translation, and protein processing. Aging decreases the expression of metabolism-related genes but increases the expression of protein processing and transcriptional genes. However, early and late aging have opposing effects on many biological processes, with 1-day-old mosquitoes having a largely different transcriptomic profile than older mosquitoes. Importantly, warmer temperature and aging interactively shape gene expression patterns, where, for example, aging-dependent changes in immune gene expression accelerate at warmer temperatures. Altogether, warmer temperature and aging, individually and interactively, alter the mosquito’s transcriptomic profile, reflecting changes in their ability to survive and overcome an infection.

overall_design:
We set out to investigate how warmer temperature and aging, individually and interactively, shape the transcriptome of naïve and immune-induced mosquitoes. To do so, we reared Anopheles gambiae (Giles sensu stricto) at 27°C, 30°C or 32°C, and allocated adult females that were 1, 5, 10, and 15 days post-eclosion to two immune treatment groups: (i) naïve and (ii) immune induced by intrathoracic injection of heat-killed Escherichia coli.
At 6 h post immune treatment we isolated RNA from pools of 15 whole-body female mosquitoes for each temperature-age combination. We completed 5 independent biological trials, resulting in 120 samples derived from 1772 mosquitoes.
We then conducted RNA-sequencing and analysis to identify how immune induction, warmer temperature, aging, and the interaction between warmer temperature and aging, alter gene expression profiles.

first: Lindsay

last: Martin

first: Jordyn

middle: S

last: Barr

first: Tania

middle: Y

last: Estévez-Lao

first: Jean-Philippe

last: Cartailler

first: Shristi

last: Shrestha

first: Julián


title: Extracellular Vesicles Derived from Mesenchymal Stromal Cells Reduce Pseudomonas aeruginosa Burden and the Inflammatory Response in Cystic Fibrosis Mouse Lung

status: Public on Jun 30 2025

city: Hanover

first: Sharanya

last: Sarkar

state: NH

address: Dewey Field Road, HB 7550

department: Microbiology and Immunology

institute: Geisel School of Medicine at Dartmouth

type: Non-coding RNA profiling by high throughput sequencing

summary: Chronic lung infections and presistent inflammation are a leading cause of morbidity and mortality in people with cystic fibrosis and therefore there is a need for therapies that can simultaneously eliminate infection and the hyperinflammatory lung environment in CF. Mesenchymal stromal cell-derived extracellular vesicles (MSC EVs) represent a promising solution, offering potent anti-inflammatory, immunomodulatory, and antimicrobial properties while being safe and non-toxic. This study demonstrates the efficacy of MSC EVs in a CF mouse model of acute Pseudomonas aeruginosa lung infection. MSC EVs reduced Pseudomonas burden, immune cell infiltration, and pro-inflammatory cytokine levels in the lungs.

overall_design: MSCs were transfected with either 1) a mimic miRNA (negative control) with no known targets in P. aeruginosa or mice or 2) miRNA let-7b-5p. EVs were isolated from the MSCs and inoculated into the lungs of CF mice with an acute P. aeruginosa infection. These smRNA-seq data are from the MSC EVs and their parent MSCs.

first: Lily

last: Taub

first: Bruce

last: Stanton

first: Barnaby

last: Roxanna


title: Transcriptomic Changes in Human Pulmonary Fibroblasts Following Microplastics Exposure

city: Krakow

first: Tomasz

last: Szmatoła

state: Małopolskie

address: Mickiewicza 21

department: OMEI

country: Poland

institute: University of Agriculture in Krakow

summary: To assess the cellular effects of polystyrene (PS) micro- and nanoparticles, human pulmonary fibroblasts (HPFs) were exposed to spherical PS particles of two diameters (100 nm and 1 µm) across multiple concentrations. For 100 nm particles, the concentrations were 0.1 g/L (A), 0.01 g/L (B), and 0.001 g/L (C); for 1 µm particles, 0.1 g/L (A), 0.05 g/L (D), 0.01 g/L (B), and 0.001 g/L (C) were tested. In summary, our data show that both particle size and concentration critically influence the cellular response to microplastics. At low concentrations (0.001 g/L), smaller particles (100 nm) induced transcriptional activation of mitochondrial and biosynthetic genes, suggesting early metabolic adaptation. In contrast, high concentrations (0.1 g/L), particularly of larger particles (1 µm), led to suppression of metabolic, mitochondrial, and proteostatic pathways, indicating functional impairment and potential cellular stress.

overall_design: HPFs were obtained from PromoCell GmbH (cat. no.: C-12360; Germany) and cultured in Dulbecco’s Modified Eagle Medium (DMEM, High Glucose; Thermo Fisher Scientific, USA), supplemented with 10% fetal bovine serum (FBS; Thermo Fisher Scientific, USA) and an antibiotic-antimycotic solution containing penicillin (10,000 U/mL), streptomycin (10,000 µg/mL), and amphotericin B (25 µg/mL; Thermo Fisher Scientific, USA). Cells were maintained at 37°C in an atmosphere containing 5% CO₂. To assess the cellular effects of PS micro- and nanoparticles, HPFs were exposed to spherical PS particles of two different diameters.  For the 100 nm particles, three concentrations were selected: 0.1 g/L (A), 0.01 g/L (B), and 0.001 g/L (C). For the 1 µm particles, four concentrations were included: 0.1 g/L (A), 0.01 g/L (B), 0.001 g/L (C) and 0.05 g/L (D) .

first: Joanna

last: Chwiej

first: Ewa

last: Ocłoń

first: Magdalena

last: Wytrwał

first: Karolina

last: Papacz

first: Igor

last: Jasielczuk

first: Artur

last: Gurgul

first: Aleksandra

last: Wilk


title: Integrated ERK-PKA-YAP/TAZ-SHH Signaling Orchestrates Cortical Radial Glia Identity and Lineage Diversification

first: TongYe

last: Fu

address: 138 Yi Xue Yuan Road

institute: Fudan University

summary: The signaling pathways governing cortical neurogenesis and gliogenesis in mice are well-defined, yet how they integrate to control the lineage progression of cortical radial glia (RGs) remains incompletely understood. Here, using mouse genetic models, it is demonstrated that ERK and PKA signaling cooperate to preserve the neurogenic capacity of cortical RGs by suppressing the gliogenic pathways YAP/TAZ and SHH. Specifically, YAP/TAZ signaling drives cortical RGs toward an ependymal fate, while SHH signaling promotes the generation of tripotential intermediate progenitor cells that produce cortical astrocytes and oligodendrocytes, and olfactory bulb interneurons. Reanalysis of published human cortical scRNA-seq data further revealed that the functional roles of these signaling pathways are conserved between mouse and human cortical RGs. Furthermore, human cortical outer RGs acquire dominant ERK/PKA signaling through a self-reinforcing loop that suppresses both YAP and SHH signaling, markedly enhancing self-renewal and extending neurogenesis. Thus, a tripartite network of ERK/PKA, YAP/TAZ, and SHH whose cross-repressive logic coordinates neurogenesis with gliogenesis and may underlie evolutionary expansion, providing a framework for understanding cortical development and evolution, is identified.

overall_design: The whole mouse cortex was dissected under a microscope for single-cell RNA sequencing (scRNA-seq) analysis. Briefly, mouse embryos and postnatal brains were collected and immediately submerged in fresh ice-cold Hanks' Balanced Salt Solution (Gibco 12175-095). The cortex was then finely dissected, cut into small pieces, and dissociated into a single-cell suspension using a Papain Cell Dissociation Kit (Miltenyi Biotec, catalog no. 130-092-628) according to the manufacturer’s instructions. Single-cell RNA-seq libraries were generated using the Chromium droplet-based sequencing platform (10X Genomics) following the manufacturer’s protocol (manual document part number: CG00052 Rev C). After cellular quality filtering, the number of cells included in the dataset were as follows: E15.0 cortex: control (Map2k1/2 without Cre), 12,128 cells, 2,673 genes/cell; Emx1-Cre; Map2k1/2-dcko mice, 9,291 cells, 2,850 genes/cell. FlashTag labling at E15.5 and FACS at E16.5: control (SuperHippo without Emx1-Cre), 13,194 cells, 2,582 genes/cell; Emx1-Cre; SuperHippo mice, 14,641 cells, 2,616 genes/cell. FlashTag labling at E15.5 and FACS at E16.5: control (wild-type littermate) brains, yielding 14,800 cells, 1,504 genes/cell, hGFAP-Cre; SuperHippo brains, yielding 13,171 cells, 1,544 genes/cell. IUE (dnPKA) labling at E15.0 and FACS at E18.0: hGFAP-Cre; SmoF/F +dnPKA, 11,508 cells, 2,369 genes/cell. FlashTag labling at P0 and FACS P2: control (SmoF/F), 14,292 cells, 2,498 genes/cell; hGFAP-Cre; SmoF/F mice, 7,694 cells, 2,681 genes/cell. FlashTag labling at P0 and FACS P2: control (SuperHippo without hGFAP-Cre), 12,054 cells, 2,258 genes/cell; hGFAP-Cre; SuperHippo mice, 11,539 cells, 2,120 genes/cell. This dataset provides a comprehensive transcriptomic landscape of cortical cells at different developmental stages under various genetic and experimental conditions

first: Zhuangzhi

last: Zhang

first: Zhejun

last: Xu

first: Tongye

first: Jialin

last: Li

first: Zhengang

last: Yang


title: Analysis of tumor infiltrating lymphocytes from murine PAN02 subcutaneos tumors under SMAC mimetic and BET inhibitor treatment

city: Vienna

first: Martin

last: Aichinger

address: Dr. Boehringer-Gasse 5-11

country: Austria

institute: Boehringer-Ingelheim

summary: A multi-omic analysis of CITE-seq and advanced flow cytometry of a syngeneic model of PDAC unveils distinct phenotypic correlations of augmented anti-tumor immunity and a substantially reduced immunosuppressive tumor microenvironment (TME). This study presents BETi and SMACm as a promising drug combination for cancer patients with a multi-layered impact on both tumor cell intrinsic, as well as TME-dependent mechanisms.

overall_design: In vivo treatment of mice harboring subcutaneous PAN02 PDAC tumors, analysis of the tumor microenvironment using CITEseq.

first: Florian

last: Ebner

first: Artem

middle: V

last: Artemov

first: Jesse

last: Lipp


title: Transposable elements function as mechanical sensors [CUT&RUN]

city: Durham

first: Tongyu

last: Sun

state: NC

address: 307 research drive

institute: Duke university

summary: Transposable elements (TEs), comprising almost half of the genome, are tightly controlled by intrinsic factors. However, how TEs are modulated by extrinsic mechanical forces remains unknown. To address this question, we culture human embryonic stem cells on hydrogels with different rigidity and comprehensively analyze the changes in transcriptome, epigenome and genome architecture of TEs, and find that TEs are able to sense mechanical forces. Upon sensing changes in substrate rigidity, a majority of TEs exhibit elevated or declined transcription, accompanied by corresponding chromatin state alterations. Moreover, mechanotransducer YAP binds directly to a subset of TEs, especially LTR7/HERV-H, and its loss partly recapitulates effects of soft substrate on TEs. Notably, mechanical forces are required for TEs’ chromatin interaction through YAP and CTCF cooperation. Functionally, mechano-sensing TE-enhancer directs definitive endoderm formation through the regulation of distal target, FAM189A2. Overall, our results demonstrate that TEs are mechanical sensors, and that TE-enhancers dictate cell fate.

overall_design: Cells were cultured on the hydrogels with different rigidity, and were collected for RNA-seq, ChIP-seq and HiCAR.

first: Yarui

last: Diao


title: Transposable elements function as mechanical sensors [ChIP-seq]


title: Hematopoietic loss of Y chromosome activates immune checkpoints to impair senescent cell clearance contributing to renal disease

status: Public on Jul 09 2025

city: Charlottesville

first: Nicholas

middle: W

last: Chavkin

address: 415 Lane Road

institute: University of Virginia

summary: The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Notably, hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan. Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease due to its well-documented connection with aging and senescence. Herein, a prospective cohort study revealed that LOY in blood is associated with an increased incidence of kidney diseases. Analyses of transcriptional signatures in human kidneys found that immune cell LOY is enriched in patients with kidney disease and associated with greater levels of cellular senescence. In mice, hematopoietic LOY led to renal dysfunction that was accompanied by senescent cell accumulation in models of kidney injury and advanced age. Accordingly, treatment with a senolytic agent promoted senolysis and preferentially inhibited the progression of renal dysfunction in LOY mice. The hematopoietic LOY condition led to the upregulation of multiple immune inhibitory receptors. Treatment with the combination of antibodies targeting PD-1 and SIRP reduced senescent cell accumulation and rescued the renal pathology conferred by hematopoietic LOY. These data indicate that hematopoietic LOY contributes to pathologic conditions by impairing the clearance of senescent cells through upregulation of immune checkpoint proteins.

overall_design: Kidney tissue was isolated from aged mice undergoing bone marrow transplantation to generate hematopoietic Control or LOY conditions, some of which were treated with Conrtol or Senolytic ABT-263 compound. Total RNA was purified, prepped for RNA sequencing, and sequenced. Raw sequencing output was aligned.

first: Yohei

last: Arai

first: Kenneth

last: Walsh


title: LKB1-deficient NSCLC cells show vulnerability to high-dose AA-induced pyroptosis.

status: Public on Jun 28 2025

city: Guangzhou

first: Xiang-yu

state: Guangdong

address: China

institute: Nanfang Hospital,southern Medical University

summary: The deficiency of LKB1 in tumor cells impairs their ability to sense metabolic stress appropriately,ultimately leading to redox imbalance. LKB1-deficient NSCLC cells predominantly take up ascorbic acid. Inflammatory PCD, including necroptosis, pyroptosis and PANoptosis, could release inflammatory mediators and switch the inflammatory state of TIME. Previous study demonstrated that high-dose AA could promote lung cancer cell death, but the modality of cell death still remained unclear. To further investigated the precise modality of the above inflammatory PCD, we performed RNA sequencing on cells with deficient or intact LKB1 pretreated with high-dose AA or not and then analyzed the established different forms of programmed cell death signaling gene.

overall_design: Gene expression profiling analysis of RNA-sequencing of A549 cells with deficient or intact LKB1 pretreated with or without high-dose AA, 3 replicates for each group.

first: Xiangyu

first: Xuejun

last: Guo

first: Xiaoting

last: Cai

first: Zhongyi

last: Dong

first: Dehua

last: Wu

first: Xue

last: Bai


title: Partial removal of visceral epididymal white adipose tissue in obese Ldlr-/-.Leiden mice alters adipokine secretion and improves cerebrovascular health

status: Public on Jul 02 2025

city: Leiden

first: Eveline

last: Gart

state: Zuid Holland

address: Sylviusweg 71

department: MHR

country: Netherlands

institute: TNO

summary: Visceral white adipose tissue (WAT) dysfunction is thought to contribute to obesity-related brain impairments but no causal relationship has been demonstrated yet. We herein investigated the impact of visceral epididymal WAT (eWAT) lipectomy on brain health and obesity-associated comorbidities (liver steatosis, atherosclerosis, WAT dysfunction) in obese Ldlr-/-.Leiden mice. To do so, high-fat diet (HFD)-fed mice with manifest obesity underwent sham surgery or partial removal (~70%) of eWAT. A separate group of mice was kept on chow diet (control). Liver disease, atherosclerosis and three WAT depots were examined histologically, and WAT biopsies were also used for ex vivo culture experiments. Brain structure and function were monitored longitudinally using neuroimaging and cognitive tests. Brain pathology was further analyzed using histological analyses and hippocampal RNA sequencing. The portion of eWAT depot which was surgically removed appeared to secrete multiple adipokines and pro-inflammatory factors ex vivo. Histological analyses at the end of the study showed that partial eWAT lipectomy had no effect on the development of liver pathology and atherosclerosis, but it reduced the number of severely hypertrophic adipocytes in the residual-eWAT. This was consistent with reduced secretion of adipokines (e.g., leptin, adiponectin) and pro-inflammatory mediators (e.g., PAI-1, MIP-1α, IL-17) in ex vivo residual-eWAT culturing experiments. Importantly, partial eWAT lipectomy also alleviated HFD-induced adverse effects on hippocampal vasoreactivity, increased cortico-hippocampal (resting-state) functional connectivity and prevented the development of sedentary behavior. Hence, partial eWAT lipectomy in mice with manifest obesity partly prevents hippocampal cerebrovascular disturbances, demonstrating a causal involvement of visceral WAT in obesity-associated brain impairments. The beneficial effects of eWAT lipectomy may, at least partly, be mediated by the observed changes in the release of adipokines and inflammatory mediators.

overall_design: At the start of the experiment the animals (Male Ldlr-/-.Leiden, fed on standard Chow diet ) were 10-12 weeks old (corresponding to young adults). A healthy control group was (Chow) was kept for 28 weeks on Chow diet (n=15). Another group was kept for 28 weeks on obesigenic energy-dense diet (HFD = High Fat Diet, n=34). At 8 weeks half of the HFD group underwent a surgical procedure to remove 70% of eWAT tissue (HFD+WATx group, n=17), while the other half underwent sham surgery (HFD+sham, n=17). Sham surgery is a similar operation as WATx without removing the WAT tissue and serves as a control for operation effects. At 28 weeks mice were sacrified and RNAseq was performed on isolated right hemisphere hippocampi totRNA.

first: Florine

last: Seidel

first: Martine

middle: C

last: Morrison

first: Ilse

last: Arnoldussen

first: Vivienne

last: Verweij

first: Joline

last: Attema

first: Christa

last: de Ruiter

first: Wim

last: van Duyvenvoorde

first: Jessica

last: Snabel

first: Bram

last: Geenen

first: Ayla

last: Franco

first: Maximilian

last: Wiesmann

first: Robert

last: Kleemann

first: Amanda

last: Kiliaan


title: Distinct Molecular Patterns in R6/2 HD Mouse Brain: Insights from Spatiotemporal Transcriptomics

status: Public on Jun 24 2025

city: Irvine

first: Ricardo

last: Miramontes

address: 845 Health Sciences Rd

institute: UC Irvine

summary: Huntington’s disease (HD) is a progressive neurodegenerative disease marked by widespread cellular disruption. To understand disease mechanisms by investigating transcriptional differences, we and others have utilized bulk and single cell transcriptomics which provide cell type information but limited spatial information. We therefore utilized 10x Genomics Visium spatial transcriptomics integrated with matched single nuclei-RNA-seq in the HD R6/2 mouse brain (postnatal day 0, 4- and 12-week) to examine disease trajectories across regions in a rapidly progressing model. Our data suggests regional, temporal and cell type specific regulatory pathways that establish distinct gene expression changes in brain. Synaptic dysfunction is observed broadly throughout the brain. We observed early dysregulation of the transcription factor Tcf-4 that may drive cortical changes. Mitochondrial deficits are the earliest changes, beginning at P0 in striatum prior to overt symptom onset together with increased expression of striatal identity genes that then become progressively downregulated. Finally, we identified a time-dependent dysregulation of neuropeptide Y signaling and potential interaction with the cAMP/PKA pathway, which may be involved in early imbalance between Drd1 and Drd2 neuron vulnerability.

overall_design: 10x Genomics FLEX snRNAseq was conducted on a rapidly progressing Huntington's disease mouse model, R6/2, and non-transgenic controls at three time points: postnatal day 0, presymptomatic 4-week and symptomatic 12-week (n=3 Males/group/genotype).

first: Mara

last: Burns

first: Jie

first: Madhu

last: Saddala

first: John

last: Reidling

first: Vivek

last: Swarup

first: Albert

last: La Spada

first: Ryan

last: Lim

first: Leslie

last: Thompson


title: Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD

city: New York

first: Li

last: Gan

state: NY

address: 413 East 69th Street, 9th Floor BB904

department: Helen and Robert Appel Alzheimer’s Disease Research Institute

institute: Weill Cornell Medicine

summary: Genetic mutations in the progranulin gene, GRN, cause frontotemporal dementia and a lysosomal storage disorder. Using single-nuclei RNA sequencing of the post-mortem brain tissue from heterozygous pathogenic granulin variant (GRN+/-) carriers we found dysregulation of microglia, phagocytosis and the phagocytic receptors MERTK and AXL. Exogenous progranulin regulated MERTK and AXL RNA expression in human microglia induced from iPSCs irrespective of GRN mutation status, without directly binding to MERTK or AXL proteins. We generated double knock-out mice and found that constitutive homozygous loss of Grn and Mertk (Grn-/-;Mertk-/-) rescued microglial disease signature while constitutive homozygous loss of Grn and Axl (Grn-/-;Axl-/-) worsened the microglial disease signature. Higher levels of AXL protein, but not MERTK protein, in the post-mortem superior temporal gyrus correlated with worse cross-sectional functional impairment (CDR sum of boxes) by both GRN+/- mutation carriers and non-carrier controls. These data explain in part the inflammation seen in GRN-FTD and are applicable to other inflammatory states in which PGRN, MERTK and AXL play regulatory roles, including cancer, sepsis, stroke, diabetes and obesity. The interaction between GRN, MERTK and AXL opens potential new therapeutic avenues to intervene on this inflammatory axis.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Droplet-based single nuclear RNA sequencing from superior frontal gyrus from 7 patients with GRN+/- loss of function mutations and 8 GRN+/+ aged controls without neurological disease; thalamic cells from WT control, single KO mice (Grn-/-, Mertk-/- and Axl-/- mice) and double KO mice (Grn-/-;Mertk-/- and Grn-/-;Axl-/-).

first: Claire

last: Clelland

last: Fan

first: Jon

middle: I

last: Etchegaray

first: Chad

middle: R

last: Altobelli

first: Sally

last: Salomonsson

first: Alisha

last: Maltos

first: Aradhana

last: Sachdev

first: Yaqiao

last: Li

first: Yungui

last: Zhou

first: David

last: Le

first: Chao

last: Wang

first: Gillian

last: Carling

first: Lay

last: Kodama

first: Faten

last: Sayed

first: Juan

last: Perez-Bermejo

first: Ethan

last: Geier

first: Jennifer

last: Yokoyama

first: Howie

last: Rosen

first: Alissa

last: Nana

first: Salvatore

last: Spina

first: Lea

last: Grinberg

first: William

last: Seeley

first: Fanny

last: Elahi

first: Michelle

last: Arkin


title: Evolution of the human autopod skeleton [Human RNA-seq]

status: Public on Aug 20 2025

first: Terence

last: Capellini

state: MA

summary: We investigate the genetic architecture of autopod development at the regulatory and transcriptomic level.

overall_design: Examination of open chromatin regions (ATAC-seq) and differentially expressed genes (RNA-seq) in the developing autopod skeleton.

first: Alexander

last: Okamoto

middle: D


title: Distinct Molecular Patterns in R6/2 HD Mouse Brain: Insights from Spatiotemporal Transcriptomics [Spatial Transcriptomics]

first: Ricardo

last: Miramontes

overall_design: 10x Genomics Visium spatial transcriptomics was conducted on brain tissue of a rapidly progressing Huntington's disease mouse model, R6/2, and non-transgenic controls at three time points: postnatal day 0, presymptomatic 4-week and symptomatic 12-week (n=2-3 Males/group/genotype).

first: Mara

last: Burns

first: Jie

last: Wu

first: Madhu

last: Saddala

first: John

last: Reidling

first: Vivek

last: Swarup

first: Albert

last: La Spada

first: Ryan

last: Lim

first: Leslie

last: Thompson


title: Drug and single-cell gene expression integration identifies sensitive and resistant glioblastoma cell populations [RNA-Seq]

status: Public on Jun 23 2025

city: Washington, DC

first: Nagi

last: Ayad

state: District Of Columbia

address: 3970 Reservoir Rd NW

department: Department of Oncology

institute: Georgetown University

summary: Glioblastoma (GBM) remains the most common and lethal adult malignant primary brain cancer with few treatment options. One of the most significant issues hindering GBM therapeutic development is intratumor heterogeneity. GBM tumors consist of multiple neoplastic cell types with distinct transcriptional profiles. Identifying compounds that target these different cell types requires a platform that predicts differential sensitivity and resistance of cells within GBM tumors. To address this, we developed a novel framework to generate tumor cell-type-specific disease signatures and their predicted drug sensitivity. We performed single-cell RNA sequencing of newly diagnosed and recurrent GBM tumors and identified compounds from the LINCS L1000 database with transcriptional response signatures selectively discordant with distinct single-cell transcriptional states within GBM tumors. We then validated in silico predictions with in vivo findings in mice as the aurora kinase inhibitor alisertib induced a shift from NPC-like to MES-like transcriptional states upon treatment. To allow other investigators to predict selective tumor cell type drug sensitivity in silico we developed a platform termed ISOSCELES (Inferred cell Sensitivity Operating on the integration of Single-Cell Expression and L1000 Expression Signatures).  Our studies suggest that ISOSCELES is a novel platform to identify cell populations that are sensitive and resistant to targeted therapies in GBM, which can inform treatment decisions in future clinical trials.

overall_design: RNA sequencing of GBM8 PDX Cells (Mayo Clinic) treated with DMSO, 100nM CT-179, or 200nM CT-179.

middle: G

first: Robert

middle: K

last: Suter


title: Transposable elements function as mechanical sensors [RNA-seq]

first: Tongyu

last: Sun

summary: Transposable elements (TEs), comprising almost half of the genome, are tightly controlled by intrinsic factors. However, how TEs are modulated by extrinsic mechanical forces remains unknown. To address this question, we culture human embryonic stem cells on hydrogels with different rigidity and comprehensively analyze the changes in transcriptome, epigenome and genome architecture of TEs, and find that TEs are able to sense mechanical forces.  Upon sensing changes in substrate rigidity, a majority of TEs exhibit elevated or declined transcription, accompanied by corresponding chromatin state alterations. Moreover, mechanotransducer YAP binds directly to a subset of TEs, especially LTR7/HERV-H, and its loss partly recapitulates effects of soft substrate on TEs. Notably, mechanical forces are required for TEs’ chromatin interaction through YAP and CTCF cooperation. Functionally, mechano-sensing TE-enhancer directs definitive endoderm formation through the regulation of distal target, FAM189A2. Overall, our results demonstrate that TEs are mechanical sensors, and that TE-enhancers dictate cell fate.

first: Yarui

last: Diao


title: Inhibition of S1PR4 and supplementation of APOM in Alport Podocytes

status: Public on Jun 20 2025

city: Miami

first: Matthew

last: Tolerico

state: FL

address: 1580 NW 10th Ave

institute: University of Miami

summary: Background: Renal lipid dysmetabolism contributes to glomerular disease progression, including Alport Syndrome. We recently identified alterations in the apolipoprotein M/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 4 signaling axis in glomeruli from patients with glomerular disease. Methods: We utilized Col4a3 knockout mice and immortalized podocytes derived from these mice as a mouse model of Alport Syndrome. Mice and podocytes were treated with recombinant apolipoprotein M or the sphingosine-1-phosphate receptor 4 antagonist, CYM50358. Results: Col4a3-/- glomeruli and podocytes exhibited reduced apolipoprotein M and increased sphingosine-1-phosphate receptor 4 expression and increased sphignsoine-1-phosphate levels, mirroring findings in patients with glomerular disease. Treatment with apolipoprotein M or CYM50358 reduced albuminuria, BUN, and plasma creatinine, and ameliorated glomerulosclerosis, tubulointerstitial fibrosis, podocyte loss and foot process effacement. Both treatments reduced triglyceride and cholesterol accumulation in glomeruli and podocytes. RNA-seq analysis of Col4a3-/- revealed that sphingosine-1-phosphate receptor 4 antagonism upregulated lysosomal and autophagy-related genes. Western blot analysis confirmed increased LC3-II/LC3-I ratios and decreased p62, indicating enhanced autophagic flux. Treated podocytes showed increased lysosome numbers and co-localization with lipid droplets. In contrast, apolipoprotein M had no effect on autophagy but promoted cholesterol efflux. Conclusions: The apolipoprotein M/sphingosine-1-phosphate axis is dysregulated in Col4a3-/- podocytes. Targeting this pathway through apolipoprotein M supplementation or sphingosine-1-phosphate receptor 4 antagonism improves renal function and reduces lipid accumulation by enhancing either cholesterol efflux or autophagy, respectively. These findings suggest that restoring lipid homeostasis via targeting the APOM/S1P/S1PR4 axis may be a promising therapeutic strategy for Alport Syndrome and other glomerular diseases.

overall_design: We treated Col4a3-/- podocytes with either a s1pr4 antagonist (CYM50358) or treated them with exogenous apolipoprotein M for 24 hours and extracted RNA

first: Alessia

last: Fornoni

first: Sandra

last: Merscher

first: Anthony

last: Griswold


title: Pharmacologic Activation of Angiotensin-Converting Enzyme II Alleviates Diabetic Cardiomyopathy in db/db Mice by Reducing Reactive Oxidative Stress

city: Gwangju

first: Woo

middle: Ju

last: JEONG

address: 123 Cheomdangwagi-ro

country: South Korea

institute: Gwangju Institute of Science and Technology

summary: Angiotensin-converting enzyme 2 (ACE2) is the main key for reducing angiotensin II (Ang II) in renin-angiotensin-aldosterone system (RAAS) inducing diabetic cardiomyopathy (DCM). ACE2 modulates cardioprotective activity not only by reducing deleterious Ang II signaling but also generating the protective peptide Ang-(1-7). Recently, several studies have reported that depletion of ACE2 worsens DCM, whereas ACE2 activation attenuates Ang II-induced cardiac dysfunction. In the present study, we aimed to evaluate the hypothesis that the enhancement of ACE2, using a US Food and Drug Administration (FDA)-approved ACE2 activator (diaminazene aceturate, DIZE), would have cardioprotective roles in a murine DCM. DIZE was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using qRT-PCR and western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM. DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse heart. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM.

overall_design: We used the murine strain with db/db mice for assessing cardiac function in diabetic. db/db mice were separated with the vehilce group and the DIZE group which is administering DIZE.

first: Sung

last: Cho

first: Chang-Myung

last: Oh

first: Raekil

last: Park

first: Donghyun

last: Kim

first: Wooju

last: Jeong

first: Yumin

first: Jibeom

last: Lee


title: Effect of depletion of Dnmt3a on gene expression during the appearance of endometriosis

city: Houston

first: Nuri

last: Sung

state: Texas

address: One Baylor plaza, Houston, Rm807

department: Molecular and Cellular biology

institute: Baylor college of Medicine

summary: Endometriosis is a benign yet invasive condition in which endometrial-like tissue grows outside the uterus. Recent evidence highlights the role of epigenetic mechanisms—particularly DNA methylation—in its development. DNA methyltransferases (DNMTs), including DNMT1, DNMT3B, and DNMT3A—regulate these modifications. DNMT3A is uniquely upregulated in the eutopic endometrium of women with endometriosis and may affect reproductive potential via altered gene expression.  To investigate DNMT3A's role, we compared the incidence of endometriosis and transcriptomic profiles in Dnmt3a knockout (KO) mice and wild-type controls. RNA sequencing of KO samples revealed upregulation of pathways such as E2F_TARGETS, MYC_TARGETS_V1, G2M_CHECKPOINT, and UNFOLDED_PROTEIN_RESPONSE, and downregulation of NOTCH_SIGNALING, COAGULATION, HEDGEHOG_SIGNALING, ANGIOGENESIS, and ADIPOGENESIS. Several immune-related genes were also differentially expressed, including IL-6, CXCL1, CXCL2, IL-1β, TNFα, CCL5, CXCL5, TGFβ1, IL-10, CXCL9, CXCL10, CX3CL1, CCL2, CCL22, CCL17, and CXCL12.  These findings suggest that elevated DNMT3A expression may contribute to immune suppression in endometriosis, and its loss leads to reactivation of immune response genes, highlighting DNMT3A as a potential therapeutic target.

overall_design: RNA-seq profiling was conducted on endometriosis samples using both wild-type DNMT3A and its knockout mice, four weeks post-disease onset.

first: Sang Jun

last: Han


title: Culture conditions differentially regulate the inflammatory niche and cellular phenotype of tracheobronchial basal stem cells

city: Glendale

first: Crystal

last: Marconett

state: CA

address: 1856 Kirkby Rd

department: Translational Genomics

institute: Keck School of Medicine

summary: Bronchial epithelial cells derived from the tracheobronchial regions of human airways (HBECs) provide a valuable in vitro model for studying pathological mechanisms and evaluating therapeutics. This cell population comprises a mixed population of basal cells (BCs), the predominant stem cell in airways capable of both self-renewal and functional differentiation. Despite their potential for regenerative medicine, BCs exhibit significant phenotypic variability in culture. To investigate how culture conditions influence BC phenotype and function, we expanded three independent BC isolates in three media: airway epithelial cell growth medium (AECGM), dual-SMAD inhibitor (DSI)-enriched AECGM, and PneumaCult Ex plus (PEx+). Analysis through RNA sequencing, immune assays, and impedance measurements revealed that PEx+ media significantly drove cell proliferation and a broad proinflammatory phenotype in BCs. In contrast, BCs expanded in AECGM and displayed increased expression of structural and extracellular matrix components at higher passage. AECGM increased expression of some cytokines at high passage, whereas DSI suppressed inflammation implicating the involvement TGF-β in BC inflammatory processes. Differentiation capacity of BCs declined with time in culture irrespective of expansion media. This was associated with an increase in PLUNC expressing secretory cells in AECGM and PEx+ media consistent with the known immune modulatory role of PLUNC in the airways. These findings highlight the profound impact of media conditions on inflammatory niche established by, and function of, in vitro expanded BCs. The broad proinflammatory phenotype driven by PEx+ media, in particular, should be considered in the development of cell-based models for airway diseases and therapeutic applications.NEW & NOTEWORTHY Airway basal cells, vital for airway regeneration and potential therapies, show significant changes based on culture conditions. Our study reveals that media composition and culture duration greatly affect basal cell properties with profound changes in the proinflammatory phenotype and extracellular matrix deposition driven by changes in growth conditions. These results underscore the critical impact of culture conditions on BC phenotype, influencing cell-based models for airway disease research and therapy.

overall_design: Basal cells were isolated from donors using established protocols and grown to 80% confluency in the specified media. Total RNA was isolated and underwent PE150 sequencing using the Illumina NovaSeq S2 at Azenta (formerly Genewiz). Data was parsed to ~43M reads per sample and pseudoaligned to the hg38 genome using Kallisto which is contanined in the processed data. Kallisto-generated BAM files were converted to .Bigwidg (processed data files).

first: Shuba

last: Murthy

first: Denise

last: Seabold

first: Lalit

last: Gautam

first: Adrian

last: Caceres

first: Rosemarie

last: Sease

middle: N

first: Amy

last: Ryan


title: Cataloging the potential functional diversity of Cacna1e splice variants using long-read sequencing

status: Public on Jul 03 2025

city: Boston

first: Shamsuddin

last: Bhuiyan

address: 60 Fenwood Rd, 7006, Hale

institute: Harvard Medical School and Brigham & Women's Hospital

summary: The degree to which alternative RNA splicing influences the function and structure of voltage gated calcium channel (VGCC) splice variants is poorly understood. Here we used long-read RNA-sequencing to catalog rat Cacna1e (Cav2.3) splice variants, and computationally prioritize which are likely to impact channel function. We sequenced Cacna1e transcripts from rat thalamus using Oxford Nanopore sequencing yielding the structure of 2,110 Cacna1e splice variants. Of these, up to 154 had the potential encode for a functional channel based on predicted amino acid sequences. Our analysis revealed a total of 31 cassette splicing events (in various combinations) potentially affecting channel function, with three cassette exons appreciably expressed and conserved.

overall_design: We characterized the splicing profile for Cacna1e using ONT RNA-seq data from the rat thalamus

first: John

last: Tyson

first: Terrance

last: Snutch

first: Paul

last: Pavlidis


title: Cell layer-specific modification of cell wall is associated with  exo-mesocarp split in pistachio (Pistacia vera L.)

status: Public on Jun 18 2025

city: Davis

first: Shuxiao

last: Zhang

address: One Shields Ave

department: Plant Sciences

institute: UC Davis

summary: Pistachio (Pistacia vera) is a drought and salinity-tolerant perennial whose fruit features a fleshy exo-mesocarp, or “hull,” that protects the kernel. Hull development and degradation are key to kernel quality, yet the anatomy and mechanisms driving hull breakdown during late-stage development remain largely unknown. Here, we show that the hull contains anatomically distinct layers of hypodermal parenchyma and filler parenchyma. Using a combination of transcriptome analyses and immunohistochemistry, we show that changes in pectin associated gene expression and modification of this polysaccharide are involved in hull cell size increase, loss of cell-cell adhesion, and softening. Anatomical analysis shows that filler parenchyma expands during late-stage hull development while hypodermal parenchyma remains constant in size. Field data suggest that irrigation and humidity affect pistachio hull split, implicating a role for water status in cell expansion. In summary, the complex interplay between molecular, cellular, and environmental changes suggests that cell layer–specific modifications of the cell wall are linked to exo-mesocarp splitting, forming a model for understanding the mechanism of fruit split during ripening in non-berry fruit crops.

overall_design: RNAseq of whole pistachio hull samples for 'Golden Hills' and 'Lost Hills' cultivars with different phenotypes (intact, cracked or tattered) collected 91 and 133 days post anthesis.

first: Minmin

last: Wang

first: Shaina

last: Eagle

first: Alisa

last: Chernikova

first: Kaleigh

middle: M

last: Bedell

first: Phuong

last: Tran

first: Chaehee

first: Jaclyn

middle: A

last: Adaskaveg

first: Yiduo

last: Wei

first: Rolando

last: Lopez

first: Annamarie

last: Basco

first: Phoebe

last: Gordon

first: Barbara

last: Blanco-Ulate

first: Grey

last: Monroe

first: Georgia

last: Drakakaki


title: The Nrf2-HMOX1 pathway as a therapeutic target for reversing cisplatin resistance in non-small cell lung cancer via ferroptosis inhibition

status: Public on Jun 17 2025

city: Nantong City

first: Lili

last: Ji

address: No.1 Build 19 Qixiu Road, Nantong City Jiangsu Province, China

institute: Medical School of Nantong University

summary: Cisplatin resistance is a major cause of poor prognosis in non-small cell lung cancer (NSCLC). Cisplatin-induced lung cancer cell death is associated with ferroptosis, a type of recently identified programmed cell death. Nrf2 is a critical component of the antioxidant system, and its pro-tumorigenic activity in lung cancer has been extensively studied. However, the role of Nrf2 in cisplatin-induced ferroptosis and drug resistance remains elusive. Here, we demonstrate that cisplatin treatment induced ferroptosis in parental A549 lung adenocarcinoma cells, and that this effect was significantly reduced in cisplatin-resistant A549/DDP cells. Knocking down Nrf2 sensitized A549/DDP cells to cisplatin-induced cytotoxicity by enhancing ferroptosis. Moreover, we demonstrated that Nrf2 promotes the expression of HMOX1, and the Nrf2-HMOX1 pathway is critical in mediating the anti-ferroptotic function. Additionally, immunohistochemical analysis of NSCLC specimens indicated that the Nrf2 expression was correlated with HMOX1, and high levels of Nrf2 and HMOX1 were associated with poor patient survival. These findings suggest that the HMOX1-Nrf2 pathway significantly influences treatment outcomes in NSCLC. Ultimately, we demonstrated that treatment with Nrf2 inhibitor ML385 promoted ferroptosis by inhibiting the Nrf2-HMOX1 pathway, restoring cisplatin sensitivity in drug-resistant cells. Our findings provide insights into the mechanism underlying cisplatin resistance and suggests that targeting the Nrf2-HMOX1 pathway enhances cisplatin-induced ferroptosis and improves NSCLC treatment outcomes.

overall_design: RNA-seq profiling of A549/DDP cells and their knockdown derivatives (shNrf2)

first: Xiaorong

last: Zhou

first: Xinru

last: Zou

first: Ling

last: Zuo

first: Shuning

last: Hu

first: Yixuan

last: Fang


title: Digital reconstruction of spatiotemporal atlas unveils the cellular origins and signaling networks underlying early mouse organogenesis

status: Public on Jun 19 2025

city: nanjing

first: yi

last: yang

address: sipailou 2

institute: southeast university

summary: Spatiotemporal gene expression and signaling orchestration are pivotal for shaping the patterns of early embryonic development. Here we profiled 360 serial sections (10-mm thickness) across 6 whole embryos during early organogenesis to generate a comprehensive spatial transcriptomic map at single-cell resolution. We developed SEU-3D to reconstruct "digital embryos", providing a virtual representation and investigation of regionalized gene expression in its native spatial context. By combining these measurements with space-informed gene-cell co-embedding analysis, we have systematically characterized the spatial atlas of endoderm and mesoderm over time, elucidating the intricate networks of cell signaling that traverse germ layers and cell types. Furthermore, we observed regionalized identity of cells along the anterior boundary between embryonic and extra-embryonic tissues of the cardiac crescent, which reflects their cellular origins, and the coordinated signaling further patterning these cells into cardiac-specific territories. Collectively, the reconstruction of single-cell resolution whole “digital embryo” provides significant insights into early mouse organogenesis, offering a unique platform for future investigations into the mechanisms underlying embryonic development.

overall_design:
Stereo-seq on whole mouse embryos at E7.5, E7.75 and E8.0 stages (replicates per stage). Replicates were OCT-embeded and sequenced together.  Samples were collected by sereal coronal sections of 10-µm thickness.
On January 18, 2026, the processed data files were updated.

first: Yi

last: Yang


title: HNRNPAB interacted with mRNAs in estrogen receptor positive (ER+) breast cancer [RIP-Seq]

city: Hefei

first: Xu

last: Junchao

state: Anhui

address: No. 443, Mount Huangshan Road, Daoxiangcun Street

institute: University of Science and Technology of China

summary: Breast cancer (BC) is the most prevailing type of cancer among women in the world. HNRNPAB belongs to heterogeneous nuclear ribonucleoproteins (hnRNPs) subfamily.In recent years, studies have found that HNRNPAB can be involved in the progression of various human cancers. It not only combines with DNA and RNA, but also mediates mRNA nuclear transport, regulates gene transcription and translation, and regulates the proliferation, migration, invasion, aging, and other phenotypes of tumor cells. HNRNPAB is closely related to the poor prognosis of cancer patients. In addition, HNRNPAB is also involved in regulating the infection process of influenza virus. It has been simply reported that the relevance of HNRNPAB as a prognostic value in BC.

overall_design: RIP assay was performed by using anti-HNRNPAB antibody (ab199724, Abcam, Cambridge, UK) and according to the manufacturer’s protocol of the EZ-Magna RIP™ Kit (17-701, Millipore, Darmstadt, Germany). Finally, RNA was purified after proteinase K digestion and extracted using TRIzol reagent (GK20008, GlpBio, California, USA). Then we sent the RIP experiment's input group and the anti-HNRNPAB antibody enrichment group to Aksomics (KangChen Bio-tech, Shanghai, China) for RIP-seq.

first: Junchao

last: Xu

first: Tao

last: Zhu


title: Transposable elements function as mechanical sensors [HiCAR]

first: Tongyu

last: Sun

overall_design: Cells were cultured on the hydrogels with different rigidity, and were collected for RNA-seq, ChIP-seq and HiCAR.

first: Yarui

last: Diao


title: The effects of FOXA1 and FOXA2 on gene expression in Ythdc1-HKO livers

status: Public on Jun 15 2025

city: Harbin

first: Zheng

last: Chen

state: Heilongjiang

address: 92 Xidazhijie  Harbin Institute of Technology

institute: Harbin Institute of Technology

summary: The goal of this study is to investigate how FOXA1 and FOXA2 regulates gene expression in Ythdc1-HKO livers. Four-week-old male Ythdc1flox/flox mice were injected with AAV8-TBG-βGal via tail vein. Four-week-old male Ythdc1-HKO mice were injected with equal amounts of AAV8-TBG-βGal, AAV8-TBG-FOXA1, or AAV8-TBG-FOXA2 via tail vein. Mice were sacrificed three weeks later.Total RNA was extracted from liver tissues using Tripure Isolation Reagent (Roche, Mannheim, Germany).  RNA-seq was performed using Illumina  novaseq x plus (n=3 for each group).

overall_design: Methods: Three independent biological replicates for each group were used for RNA-seq. RNA-seq was performed by deep sequencing using an Illumina  novaseq x plus. Paired-end clean reads were aligned to the mouse reference genome(grcm39) with Hisat2 (2.2.1), and the aligned reads were used to quantify mRNA expression by using featureCounts (2.0.6).

first: Xinzhi

last: Li