title: Spatial Transcriptomic Profiling of the Mouse Adrenal Gland and Adjacent Adipose Tissue

status: Public on Aug 07 2025

city: Poznan

first: Marcin

last: Rucinski

address: Swiecicki 6

department: Histology and Embryology

institute: Poznan University of Medical Sciences

summary: This study employs spatial transcriptomics to map the molecular landscape of the mouse adrenal gland, focusing on distinct cortical zones (zona glomerulosa, zona fasciculata, X-zone) and the adrenal medulla, as well as adjacent adipose tissue. Using Visium CytAssist technology, we analyzed adrenal sections from male CD-1® IGS mice, identifying seven distinct cell clusters, including brown and white adipose tissues.

overall_design:
Four sexually mature male CD-1® IGS mice, 10 weeks old with a body weight of approximately 37 g were used in this study.  Mice were housed in colony cages in a pathogen-free environment with temperature maintained at 21-23°C and relative humidity between 55-60% and under a 12h light/12 h dark cycle. All mice were given standard chow and water ad libitum. The mice were euthanized by decapitation and the harvested adrenals were immediately preserved in 10% buffered formalin for further analysis.
Grant ID: 2020/38/E/NZ4/00020
Grant title: The role of MOTS-c peptide in the regulation of adrenal cortex physiological function
Funding source: National Science Centre, Poland (NCN)
Grantee: Marcin Rucinski

first: Małgorzata

last: Blatkiewicz

first: Szymon

last: Hryhorowicz

first: Marta

last: Szyszka

first: Joanna

last: Suszyńska-Zajczyk

first: Andrzej

last: Pławski

first: Adam

last: Plewiński

first: Andrea

last: Porzionato

first: Ludwik K.

last: Malendowicz


title: Subnuclear genome compartmentalization controls bivalent chromatin activity [RNA-seq]

status: Public on Aug 06 2025

city: San Francisco

first: Mitchel

last: Cole

state: CA

address: 35 Medical Center Way

department: Neurological Surgery

country: USA

institute: UCSF

type: Expression profiling by high throughput sequencing

summary: The nuclear genome is spatially organized into a three-dimensional architecture by physical association of large chromosomal domains with subnuclear compartments including the nuclear lamina at the radial periphery and nuclear speckles within the nucleoplasm1,2,3,4,5. However, how higher-order spatial genome architecture regulates human development has been overlooked, and the interplay between chromatin state and subnuclear genome compartmentalization is poorly understood. Here we generate high-resolution maps of genomic interactions with the lamina and speckles in cells of the neurogenic lineage isolated from mid-gestational human cortex, identifying an intimate association between subnuclear genome compartmentalization, chromatin state and transcription. During cortical neurogenesis, subnuclear genome compartmentalization is extensively remodelled, relocating hundreds of neuronal genes from the lamina to speckles, including key neurodevelopmental genes bivalent for trimethylation of histone H3 at Lys27 (H3K27me3) and Lys4 (H3K4me3). At the lamina, bivalent genes have exceptionally low expression, and relocation to speckles enhances resolution of bivalent chromatin to H3K4me3 monovalency and increases transcription more than eightfold. We further demonstrate that proximity to the nuclear periphery—not the presence of H3K27me3—maintains the lowly expressed, poised state of bivalent genes embedded in the lamina. We find that the repressive environment of the lamina is associated with spatial segregation of the transcriptional elongation machinery from the nuclear periphery. Our results establish a paradigm in which knowing the spatial location of a gene is necessary for understanding its epigenomic regulation.

overall_design: RNA-seq of iPSC-derived NPCs and iPSC-derived neurons (iN); RNA-seq of ESC-derived NPCs treated with DMSO or EZH2 inhibitor, EPZ-6438

first: Chujing

last: Zhang


title: Subnuclear genome compartmentalization controls bivalent chromatin activity

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design:
LaminB1 GO-CaRT followed by sequential ChIP (LaminB1 GO-CaRT.ChIP-reChIP) and H3K27me3/H3K4me3 CUT&RUN of iPSC-derived NPCs; LaminB1 CUT&Tag, H3K27me3/H3K4me3 CUT&Tag of iPSC-derived NPCs and iPSC-derived neurons (iN); LaminB1 GO-CaRT and H3K27me3/H3K4me3 CUT&RUN of ESC-derived NPCs treated with DMSO or EZH2 inhibitor, EPZ-6438; H3K27me3 CUT&RUN and LaminB1 GO-CaRT of HEK293T cells with or without Fab blocking

**Raw data for human tissue deposited in dbGAP**


title: Transcriptome analysis of liver tissue from patients with Autoimmune Hepatitis, Primary Biliary Cholangitis, and Chronic Hepatitis B

city: Huzhou

first: Yunliang

last: Yao

state: Zhejiang

address: 759 East Second Ring Road

department: Medical School

country: China

institute: Huzhou Normal University

summary: This study aims to identify immune-related genes in Autoimmune Hepatitis (AIH) by analyzing liver tissue transcriptomes. Bulk RNA sequencing was performed on liver biopsies from patients with AIH and two disease control groups: Primary Biliary Cholangitis (PBC) and Chronic Hepatitis B (CHB). Differential expression analysis was used to compare AIH against both control groups. By intersecting the resulting differentially expressed genes (DEGs) with immune gene databases, we identified 19 common immune-related DEGs (IRDEGs). Gene Ontology (GO) analysis of these genes highlighted functions related to lymphocyte-mediated immunity and T-cell receptor signaling. This dataset provides a resource for exploring liver gene expression changes in AIH.

overall_design: Overall Design: Bulk RNA sequencing was used to compare liver tissue transcriptomes from three patient cohorts: Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), and Chronic Hepatitis B (CHB). Sample Processing and Sequencing: Total RNA was isolated from residual liver biopsy tissues. Strand-specific libraries were prepared using the Illumina TruSeq Stranded Total RNA kit and sequenced on an Illumina NovaSeq 6000 platform. Data Analysis: Differentially expressed genes (DEGs) between the AIH group and the two control groups (PBC and CHB) were identified using the DESeq2 R package. The significance threshold was set at a p-value < 0.05 and an absolute log2 fold change > 1.

first: Jiapeng

last: Gao


title: PFOS perturbs mitochondrial metabolism in skeletal muscle in vivo

status: Public on Aug 01 2025

city: Clemson

first: William

last: Baldwin

state: SC

address: 132 Long Hall

institute: Clemson University

summary: The purpose of this project was to investigate the effects of PFOS on skeletal muscle in vivo. To perform this work, Cyp2b-null and hCYP2B6-Tg mice were treated with 0, 1, or 10 mg/kg/day PFOS for 21 days. Gastrocnemius muscle was collected during necropsy and various assays were performed. RNA seq was performed to determine what gene expression changes occured due to PFOS treatment and the difference between genotypes.

overall_design: Male and female Cyp2b-null and hCYP2B6-Tg mice (n = 3-5) were treated with 0, 1, or 10 mg/kg/day PFOS via oral gavage for 21 days. Mice were euthanized via carbon dioxide asphyxiation followed by heart puncture. Gastrocnemius muscle was collected and snap frozen in liquid nitrogen.

first: Jazmine

middle: A

last: Eccles-Miller

middle: S

first: Lanie

last: Williams


title: Comparative Analysis of the Transcriptome and Methylome in Distinct Trophoblast Populations During Embryo Implantation in Mares

status: Public on Aug 05 2025

city: Olsztyn

first: Dawid

last: Tobolski

state: Warmińsko-mazurskie

address: Kazimierza Jaroszyka

department: Department of Large Animal Diseases and Clinic

country: Poland

institute: Institute of Veterinary Medicine, Warsaw University of Life Sciences

type: Methylation profiling by high throughput sequencing

summary:
Abstract Background During equine implantation, two trophoblast subpopulations are distinguished: the invasive (chorionic girdle) and non-invasive (allantochorion). The invasive chorionic girdle is believed to interact with the maternal immune system and contribute to embryo attachment to the endometrium. However, the mechanism regulating attachment and immune tolerance to these two distinct trophoblast subpopulations remain incompletely understood. The present study aimed to investigate the regulation of gene expression and the biological processes involved in trophoblast attachment, development and maintenance of immune tolerance by comparing the transcriptomes and methylomes of the allantochorion and chorionic girdle trophoblast before and after implantation, that is, between days 33 and 42 of gestation. Results Irrespective of gestational day, allantochorion (N=4) was enriched in TGFB and its receptors TGFBR1 and TGFBR2. Across implantation, expression of regulatory macrophage markers, as IL33, IL4|1, PLG-RKT, or CD163, also increased in that membrane in addition to TFEB and SERPINE1. Invasive chorionic girdle (CG33, N=4) had higher, than the non-invasive allantochorion (ALC33, N=4), expression of NLRC5, a transcriptional regulator of MHC I, and expression of that factor further decreased in allantochorion from gestational day 33 to 42. Furthermore, B2M, which encodes the MHC I light chain, was hypermethylated in the allantochorion. Some genes were differentially methylated and expressed between the two trophoblasts (CAVIN1, LHB, INSR) or beginning and end of implantation (IFNGR1, CD177). Analysis of GOterms and canonical pathways showed that both differentially expressed and methylated genes were involved in critical for implantation processes and pathways as these including cell movement and adhesion, TGFB signaling, fibrosis, wound healing, or leukocyte extravasation.   Conclusions Allantochorion may contribute to the formation of the attachment with the endometrium and maintenance of maternal tolerance. Expression of IL33, IL4|1 or CD163 suggests involvement of regulatory macrophages in the implantation. TFEB might be involved in the support of allantochorion steroidogenic functions and maturation. Spatial-temporal differential methylation of genes expressed by the chorionic girdle and allantochorion may contribute to the control of trophoblast invasion and its attachment to endometrium.  Finally, methylation of B2M and differential expression of NLRC5, are involved in the control of MHC I expression on equine trophoblasts during implantation.
Background: During equine implantation, two distinct trophoblast subpopulations are identified: the invasive chorionic girdle (CG) and the non-invasive allantochorion. The invasive CG is believed to modulate the maternal immune response and facilitates embryo attachment to the endometrium, while the allantochorion contributes to placental development without breaching the endometrium. However, the mechanisms underlying differential adhesion and immune modulation by these two lineages remains poorly understood. This study aimed to investigate the regulation of biological processes underlying trophoblast attachment, development and maintenance of immune tolerance by comparing the transcriptomes and methylomes of CG and allantochorion trophoblasts before and after implantation, that is, between gestational days 33 and 42. Results: Irrespective of gestational day, allantochorion (n=4) was enriched in TGFB and its receptors TGFBR1 and TGFBR2. Across the implantation window, expression of regulatory macrophage markers such as IL33, IL4|1, PLG-RKT, and CD163 increased in the allantochorion, along with upregulation of TFEB and SERPINE1. The invasive GC (CG33, n=4) showed higher expression of NLRC5, a transcriptional regulator of MHC I, compared to the non-invasive allantochorion (ALC33, n=4). Notably, NLRC5 expression declined in the allantochorion from day 33 to 42. Furthermore, B2M, which encodes the MHC I light chain, was hypermethylated in the allantochorion. Several genes, including CAVIN1, LHB, and INSR, were both differentially expressed and methylated between the two trophoblast types, while others, such as IFNGR1, CD177, showed differential regulation across the implantation window. Gene Ontology and pathway analyses revealed that differentially expressed and methylated genes were enriched in biological processes and pathways critical for implantation, including cell migration and adhesion, TGFB signaling, fibrosis, wound healing, and leukocyte extravasation.Conclusions: The allantochorion plays an active role in establishing the attachment to the endometrium and sustaining maternal immune tolerance during implantation. The upregulation of IL33, IL4|1, and CD163 suggests the that the allantochorion may promote the recruitment or polarization of macrophages toward a regulatory phenotype, thereby modulating the local immune environment. TFEB may contribute to the steroidogenic activity and functional maturation of the allantochorion. Spatial and temporal differences in gene methylation between CG and allantochorion suggest involvement of epigenetic regulation in trophoblast invasion and attachment to the endometrium. Finally, combined B2M hypermethylation and differential expression of NLRC5 point to epigenetic and transcriptional control of MHC I expression in the equine trophoblasts during implantation.

overall_design: Equine allantochorion (ALC) and chorionic girdle (CG) samples  were collected with non-surgical uterine lavage at gestational days 33 (N ALC =4; N CG=4) and 42 (N=4) from physiologically progressing pregnancies. RNA was isolated from each sample using PureLink™ RNA Mini Kit (Ambion) with DNAse digestion between washing. Its quality and quantity were measured on a NanoDrop2000 and a TapeStation 2200 system (RNA tapes, Agilent). Acceptable samples had an RIN over 9.5. According to the manufacturer's protocol, cDNA libraries cells were prepared using the VAHTS Universal V8 RNA-seq Library Prep Kit for Illumina from 300 ng aliquots of purified RNA samples. The final cDNA library concentration was 10 nM. The quality and quantity of cDNA libraries was assessment using D1000 tapes on TapeStation2200 and on Quibit. The cDNA were sequenced over 150PE cycles on a HiSeq 3000 System (Illumina, San Diego, CA, USA) in outdoor facilities (Admera Health Biopharma Services).

last: Jaworska

first: Tomasz

last: Szmatoła

first: Katarzyna

last: Ropka-Molik

last: Ząbek

first: Anne

last: Kahler

first: Shebl

last: Salem

first: Izabela

last: Wocławek - Potocka

last: Piórkowska

first: Amanda

last: De Mestre


title: Epigenetic Editing Balances TCR Suppression and Persistence in CAR T cells

city: Dresden

first: Frank

last: Buchholz

address: Tatzberg 47/49

department: UCC / Medical Faculty and University Hospital Carl Gustav Carus

country: Germany

institute: Technische Universität Dresden

summary: Allogeneic chimeric antigen receptor (CAR) T cell therapies offer a scalable, off-the-shelf option for cancer treatment, but their clinical use is limited by the risk of graft-versus-host disease (GvHD), mediated by the endogenous T cell receptor (TCR). Conventional strategies to eliminate TCR expression rely on genome editing tools such as CRISPR/Cas9 or base editing, which introduce permanent DNA changes and pose safety concerns. Here, we present an epigenetic editing approach that enables efficient, specific, and reversible silencing of the CD3ε gene, a critical component of the TCR complex, without altering the genome. Through systematic optimization of the epigenetic editor and guide RNA design, we achieved robust TCR silencing in primary T and CAR T cells while preserving CAR expression, activation, and effector function. Transcriptome analysis confirmed minimal off-target effects. In vivo observation suggest the epigenetically silenced T cells to prevent GvHD while persisting longer than TCR-knockout cells, supporting the notion that transient TCR suppression may help balance safety and long-term efficacy. Our findings establish epigenetic editing as a non-genotoxic alternative to genome editing, offering a flexible and safer route to generate next-generation allogeneic CAR T cells.

overall_design: RNA-seq profiling of human T cells samples from the same donor which were either untreated, mock electroporated, CRISPR/Cas9 TRAC knocked out or CD3E epigenetically silenced

first: Pascal

middle: Y

last: Schönberg

first: Ángela

middle: M

last: Ovalle

first: Haidy

last: Saleh

first: Eugenia

last: Crespo

first: Anja

last: Feldmann


title: Detection of statistically robust interactions from diverse RNA-DNA ligation data [nucRNA-seq]

city: Frankfurt

first: Simonida

last: Zehr

state: Hesse

address: Theodor-Stern-Kai 7

department: Institute for Cardiovascular Physiology

institute: Goethe University, Frankfurt am Main, Germany,

summary: Chromatin-localized RNAs play diverse roles in gene regulation and nuclear architecture. Mapping genome-wide RNA-DNA interactions is possible using a variety of molecular methods, including using bridging oligonucleotides to ligate RNA and DNA in proximity. While molecular methods have progressed, a robust computational method for calling biologically meaningful RNA-DNA interactions from these data is lacking. Herein, we present RADIAnT, a reads-to-interactions pipeline for analyzing RNA-DNA ligation data. RADIAnT calls interactions against a dataset-specific, unified background which considers RNA binding site-TSS distance and genomic region bias. By scaling the background with RNA abundance, RADIAnT is sensitive enough to detect specific interactions of lowly expressed transcripts, while remaining specific enough to discount false positive interactions of highly abundant RNAs. RADIAnT outperforms previously proposed methods in the accurate recall of genome-wide Malat1-DNA interactions, and in a use-case, was utilized to identify dynamic chromatin-associated RNAs in the physiologically- and pathlologically-relevant process of endothelial-to-mesenchymal transition.

overall_design: nucRNA-sequencing was performed on 3 HUVEC replicates, once in wildtype (endothelial) phenotype (CTL), once after IL-1β + TGF-β induced phenotypic switch to mesenchymal-like cells (EMT).

first: Sandra

last: Seredinski

first: Matthias

last: Leisegang

first: Ralf

middle: P

last: Brandes

first: Marcel

middle: H

last: Schulz

first: Timothy

last: Warwick


title: A-to-I editing and adr mutant gene expression in C. elegans germlines

city: BLOOMINGTON

first: Emily

middle: Ann

last: Erdmann

state: IN

address: 1001 E Third Street

department: Biology

institute: Indiana University

summary: In this study, we performed high-throughput RNA-seq on young adult germline samples from wild-type and adr-2(-) C. elegans hermaphrodites. A-to-I editing sites were identified using SAILOR. Differential gene expression analysis was performed using DESeq2.

overall_design: Germlines were isolated from synchronized young adult C. elegans hermaphrodites raised at 20 degrees C. Strains used include N2 and BB20 (adr-2(ok735)). RNA was extracted and poly-A selection was performed prior to library preparation.

first: Heather

last: Hundley


title: Detection of statistically robust interactions from diverse RNA-DNA ligation data [ATAC-seq]

overall_design: ATAC-sequencing was performed on 3 HUVEC replicates, once in wildtype (endothelial) phenotype (CTL), once after IL-1β + TGF-β induced phenotypic switch to mesenchymal-like cells (EMT).


title: Detection of statistically robust interactions from diverse RNA-DNA ligation data [RADICL-seq]

overall_design: RADICL-sequencing was performed on HUVEC batch 405Z013, once in wildtype (endothelial) phenotype (CTL), once after IL-1β + TGF-β induced phenotypic switch to mesenchymal-like cells (EMT).


title: Hidden stop codons dictate mRNA fate by ambushing ribosomal frameshifting

status: Public on Jul 31 2025

city: Kunming, Yunnan

first: fei

last: li

address: Dongwaihuan South Road, University Town, Chenggong District, Kunming City, Yunnan Province

institute: Yunnan university

summary: In eukaryotes, the intrinsic mRNA stability is generally dictated by codon usage bias, the uneven preferences for synonymous codons, in a translation-dependent manner. However, the conserved mechanism underlining this phenomenon remains elusive. Hidden stop codons (HSCs), which are stop codons located in the +1 or -1 frame relative to canonical open reading frames (ORF), are sidespread across all genomes but have long been overlooked. We demonstrate that in both fungi and mammals, HSCs play an important role in regulating mRNA decay across the genome by immediately terminating out-of-frame translations promoted by nonoptimal codons, primarily through +1 ribosomal frameshifting. In the filamentous fungus Neurospora, partially deleting HSCs via synonymous substitutions in the clock gene frequency disrupts the circadian rhythm due to increased mRNA stability. Similarly, in human cells, impaired translation termination caused by rapid depletion of eRF1 leads to globally increased stability of mRNAs enriched with non-optimal codons and HSCs, which are in part degraded through the NMD pathway via UPF1. Given that from yeasts to humans the occurrence of HSCs is genome-widely associated with the presence of nonoptimal codons, these findings suggest that in eukaryotes, HSCs might coevolve with codon usage to modulate mRNA stabilities via immediately terminating different levels of ribosomal frameshifting events promoted by nonoptimal codons.

sample_organism:
Neurospora crassa
Homo sapiens

platform_organism:
Neurospora crassa
Homo sapiens

overall_design:
SLAM-seq assay was performed for HCT116 cell line and N. crassa strains ( WT and upf1 KO) to observe mRNA decay profile.  Timepoints: 0, 10, 20, 40, 60 minutes.
Ribo-seq assay was performed for WT and eRF1 KD HCT116 cell line

first: Zhanbiao

last: Li

first: Shimin

last: Gong

first: Yunkun

last: Dang


title: A Spatial and Temporal Transcriptomic Atlas of Mouse Intestinal Regeneration in the Jejunum

status: Public on Jul 29 2025

city: Piscataway

first: Verzi

last: Michael

state: New Jersey

address: 145 bevier road

department: Genetics

institute: Rutgers University

summary: The highly proliferative intestine is prone to damage, making it an ideal model for studying tissue regeneration. We performed spatial transcriptomics to characterize intestinal healing over a six-day period, revealing shifts in the spatial organization of epithelial and stromal cell populations, as well as changes in gene expression patterns and functional roles across tissue compartments. Furthermore, our analysis recapitulates known features of intestinal regeneration, highlighting the robustness of the dataset and its value as a resource for developing novel therapeutic strategies.

overall_design: 23 C57BL/6J mice were included in the study to generate 4 spatial transcriptomics datasets. Mice were treated with 12Gy whole-body irradiation (IR). Control (non-IR) mice, and mice post-IR days 1 through 6 were analyzed using Visium HD spatial transcriptomics. The platform uses near-genome scale probes to capture transcripts within a 2x2um array. A supplementary file (README_spatial_data_guide.pdf) is provided with instructions for accessing the datasets, and includes a description of the treatment post-IR per mouse, per each dataset.

first: Rachel

last: Ofer

first: Tyler

last: Tran

first: Ping

last: He

first: Xia

last: Qiu

first: Xinyu

last: Hu

first: Emmanual

last: Zachariah

first: Curtis

last: Krier

first: Ankit

last: Saxena

first: Lei

last: Chen

first: Jiekun

last: Yang

first: Michael

last: Verzi


title: Transcriptomic Analysis of iPSC-derived Cortical Neurons Under TSA and Aβ Treatment

city: Indianapolis

first: Madeline

last: Peyton

address: 410 W 10th St

summary: This study investigates the transcriptional effects of TSA and Aβ oligomers on human neuronal cells using RNA sequencing of iPSC-derived cortical neurons subjected to various treatment conditions. The experimental design included four distinct groups: untreated control, TSA treatment alone, Aβ exposure alone, and combined TSA treatment and Aβ exposure. Each condition was evaluated with four biological replicates, with an additional technical replicate for each condition to assess reproducibility.

overall_design: RNA-seq analysis of iPSC-derived cortical neurons with 4 treatment conditions: (1) Control (untreated), (2) TSA treatment alone (60 ng/ml), (3) Aβ oligomer exposure alone (5 μM), and (4) Combined TSA pre-treatment (60 ng/ml for 24h) followed by Aβ oligomer exposure (5 μM). Cells were treated at DIV 4 and RNA was extracted using Total RNA Purification Kit. Four biological replicates per condition with additional technical replicates.

first: Travis

last: Johnson


title: Multiomics analyses reveal the role of Glis3 in polycystic kidney disease

status: Public on Jul 30 2025

city: New Haven

first: Stefan

last: Somlo

state: CT

address: 333 Cedar Street

institute: Yale University

summary: We performed unbiased transcriptional profiling and chromatin accessibility analyses on adult kidney tissues from allelic series of Pkd1 and Glis3 inactivation mouse models. Glis3 is a modifer of cyst progression whose inactivation exacerbates polycystic kidney disease. Through the integration of multiomic datasets, we generated hypotheses to explain the worsening phenotype observed in Pkd1 and Glis3 double mutants.

overall_design: We performed RNA-Seq and ATAC-Seq on the same kidney tissues using the following genotypes: wild type, Glis3fl/fl; Pax8rtTA; TetOCre (Glis3KO), Pkd1fl/fl; Pax8rtTA; TetOCre (Pkd1KO), and Glis3fl/fl; Pkd1fl/fl; Pax8rtTA; TetOCre (Pkd1KO+Glis3KO). All mice received oral doxycycline from postnatal day 28 to 42 (P28-P42) and kidney tissues were harvested at P49 (7 weeks).

first: Zemeng

last: Wei


title: Pulsatile stretch stimulates endothelial PDGFB secretion to maintain arterial vascular smooth muscle

city: Dallas

first: Thomas

last: Carroll

address: 6000 Harry Hines Blvd.

institute: UT Southwestern

summary: The endothelial cells (ECs) that line blood vessels are remarkably sensitive to mechanical force. Hemodynamic force impacts ECs in three dimensions: laminar shear stress, intraluminal pressure, and circumferential stretch. The magnitude of these forces in arteries is pulsatile in nature—a quality that is lost in veins. The role of pulsatility in shaping these vessels is not well understood. Here we examine loss of pulmonary arterial pulsatility following the Glenn surgery (surgical palliation of single ventricle congenital heart disease). Using cultured pulmonary arterial ECs, we define the transcriptional changes driven by pulsatility within each dimension. We identify pulsatile stretch as a critical stimulus for endothelial secretion of PDGFB—a known driver of vascular smooth muscle cell (VSMC) proliferation—and show that loss of arterial pulsatility in vivo leads to thinning of VSMCs. This work provides a mechanistic understanding of how arterial pulsatility maintains the structure that supports arterial hemodynamic force.

overall_design: Human pulmonary artery endothelial cells (HPAECs) exposed to either static, pulsatile, or non-pulsatile conditions of flow, stretch, or pressure

first: Stephen

last: Spurgin

first: Chris

last: Cheney

first: Ondine

last: Cleaver


title: Single-Cell Transcriptional Analysis of Murine Mesenteric Lymph Nodes Following Oral Lyso-phosphatidylserine Nanoparticle Administration Reveals Cellular Heterogeneity in Tolerance Features

city: Buffalo

first: Jonathan

middle: E

last: Bard

state: New York

address: 701 Ellicott Street

department: Genomics and Bioinformatics Core

institute: University at Buffalo

summary: Unwanted immune responses against self-proteins or exogenous therapeutic proteins can trigger autoimmune diseases or compromise the safety and efficacy of life-saving therapeutic biologics. To address this issue, we utilized the ability of phosphatidylserine (PS) to convert an immunogen into a tolerogen and rationally developed a LysoPS-containing tolerogenic nanoparticle platform to prevent and mitigate unwanted immune responses. We demonstrated that prophylactic oral treatment with LysoPS-containing proteins prevents unwanted immune responses by inducing tolerance. However, the biological processes and cellular communication involved in LysoPS-mediated oral tolerance remain unclear. Therefore, this study aimed to characterize immune cell interactions and the potential tolerogenic mechanism in mice treated with LysoPS using Single-cell RNA sequencing (scRNA-seq). Our data showed that LysoPS nanoparticles increased the expression of RNAs associated with tolerogenic features in B cells, T cells, and NK cells, primarily through TGF-β responses.

overall_design: Animals were continuously fed Buffer, Free OVA, and LysoPS-OVA for four weeks via oral administration. Mesenteric lymph nodes (MLNs) were collected, enzymatically digested, and purified into a single live cell suspension before scRNA-seq. Six animal per group were used in this study and animal from the same group were pooled together for scRNA

first: Vincent

last: Chak

first: Edwin

middle: J

last: Ovalle

first: Elizabeth

last: Wohlfert

first: Jason

middle: G

last: Kay

first: Sathy

last: Balu-Iyer


title: single cell RNA-seq of CD45+ cell from DSS induced colitic

status: Public on Jul 28 2025

city: Fuzhou

first: Qingxiang

last: Gao

state: FuJian

address: Qiuyang Road No1.

institute: Fujian University of Traditional Chinese Medicine

summary:
Objective: Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn’s disease (CD), represents a challenging group of chronic gastrointestinal inflammatory disorders. While trained immunity, a form of innate immune memory, has shown promise in combating infection and cancer, its role in chronic inflammatory diseases, particularly inflammatory bowel disease (IBD), remains relatively underexplored. This study aims to investigate the potential of trained immunity to ameliorate IBD.
Results: BG induced trained immunity significantly ameliorates DSS-induced colitis. Mechanistically, β-glucan primed the hematopoietic compartment, leading to a profound shift in monocyte fuction. Both bone marrow transplantation from trained donors to naïve recipients and adoptive transfer of trained peripheral monocytes provided protection against DSS colitis. Notably, trained mice displayed enhanced bactericidal activity against intestinal bacterial infections. Furthermore, single-cell RNA sequencing revealed that β-glucan-induced trained immunity resulted in an expansion of reparative Cx3cr1 intestinal macrophages originating from Ly6Chi monocytes, facilitating faster recovery of the colon epithelium.
Conclusion: Our findings demonstrate that β-glucan effectively induces trained immunity, leading to a multifaceted protective response against experimental colitis. These findings provide compelling evidence for the therapeutic potential of harnessing trained immunity to treat IBD and offer a novel approach to modulating intestinal inflammation and restoring gut homeostasis。

overall_design: Mice were i.p. injected with one dose of BG (1 mg) on day -7 (designated day0, D ), Then, Mice received 3% indicated DSS (36,000 to 50,000 molecular weight; MP Biomedicals) in their drinking water for 5 days, followed by 2 days(D7).

first: Yinyin

last: Lv

first: Qiongyun

last: Chen


title: Genetic etiology and phenotypic characteristics of fetuses with 11q deletion (11q23.3-q25) syndrome

status: Public on Jul 21 2025

city: Shenzhen

first: Tong

last: Zhang

address: Longgang District Maternity & Child Healthcare Hospital of Shenzhen City

summary:
To investigate the clinical phenotype, genetic etiology, and diagnosis of 11q deletion (11q-) syndrome.
The differences and severity of fetal phenotypes may depend on the types and quantities of functional genes contained in fragments of different sizes.

overall_design: In this study, pregnant women were selected from prenatal testing in Longgang Maternal and Child Health Hospital of Shenzhen. After screening for prenatal serological analysis, noninvasive prenatal genetic testing screening (NIPS), chromosome karyotype analysis, and chromosome microarray analysis (CMA), 4 pregnant women diagnosed with 11q- syndrome were selected for retrospective analysis.

first: Weiqiang

last: Liu


title: Enhancing Non-Small Cell Lung Cancer Treatment Utilizing Natural Killer Cell-Derived Extracellular Vesicles (NKEVS) As A Novel Adoptive Cellular Therapeutic [tumor]

status: Public on Jul 09 2025

city: Phoenix

first: Eric

last: Alsop

state: AZ

address: 445 N. Fifth Street

institute: TGen

summary: An established mechanism contributing to Immune Checkpoint Inhibitor (ICI) therapy failure is tumor evasion of T-cell responses via downregulation of human leukocyte antigen (HLA). Conversely, the effector function of Natural Killer (NK) cells is enhanced in the absence of HLA expression, making NK-based cellular therapies an attractive option for tumors that are resistant to ICIs. We investigated the preclinical efficacy of using selective isolation of NK cells and harvesting of NKEVs in NSCLC. Single-cell RNAseq (scRNAseq) was used to examine the cellular landscape in PBMCs and tumor tissue. NK cells were isolated from PBMCs, expanded in vitro, and NK-derived EVs (NKEV) were collected and the EV RNA and protein cargo was characterized using proteomics and transcriptomics. The functional capabilities of patient derived NKEVs were assayed with 3-dimensional organoid-like structures derived from patient tumor cells.  This work described the cellular landscape in NSCLC circulating and tumor infiltrating immune cells. Additionally, it demonstrated that NKEVs can be successfully harvested from patient derived, expanded NK cells, and highlighted their anti-tumor properties in combination with standard-of-care therapies.

overall_design: Samples from NSCLC patients (n=10) enrolled in the study were collected at Baylor Scott and White, by trained medical personnel. Specifically, a blood sample was collected pre- and post- tumor resection surgery, and PBMCs were isolated via density gradient separation. From the tumor resection, whatever tissue was left behind after pathology and diagnostic tests, was snap frozen in preparation for scRNAseq. Everything was collected, and kept frozen at Baylor Scott and White, and shipped to the Translational Genomics Research Institute for analysis.

first: Ronan

last: Kelly

first: Kendall

last: Van Keuren Jensen

first: Joanna

last: Palade


title: Enhancing Non-Small Cell Lung Cancer Treatment Utilizing Natural Killer Cell-Derived Extracellular Vesicles (NKEVS) As A Novel Adoptive Cellular Therapeutic [EV RNA]

overall_design: Samples from NSCLC patients (n=10) enrolled in the study were collected at Baylor Scott and White, by trained medical personnel. Specifically, a blood sample was collected pre- and post- tumor resection surgery, and PBMCs were isolated via density gradient separation. From the tumor resection, whatever tissue was left behind after pathology and diagnostic tests, was snap frozen in preparation for scRNAseq. Everything was collected, and kept frozen at Baylor Scott and White, and shipped to the Translational Genomics Research Institute(TGen) for analysis. At TGen, PBMCs were thawed, the NK cells were isolated via negative selection and magnetic beads, and cultured in suspension for 2-4 weeks. Cell culture medium was retrieved every 48 hours, and size exclusion chromatography was used to isolate the extracellular vesicles.


title: Enhancing Non-Small Cell Lung Cancer Treatment Utilizing Natural Killer Cell-Derived Extracellular Vesicles (NKEVS) As A Novel Adoptive Cellular Therapeutic [PBMC]


title: Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumours

status: Public on Jul 07 2025

city: New York

first: Laszlo

last: Halasz

state: NY

address: 1470 Madison Avenue

department: Department of Oncological Sciences

institute: Mount Sinai Icahn School of Medicine

summary: Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME) and tumour-enhanced myelopoiesis in the bone marrow fuels these populations. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression. NRF2 activity is amplified during monocyte differentiation into mo-macs in the TME to regulate stress and drive immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced the survival and immunosuppression of mo-macs in the TME, restoring natural killer and T cell anti-tumour immunity and enhancing checkpoint blockade efficacy. Our findings identify a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the lung TME and highlight the potential of early interventions to reprogram macrophage fate for improved immunotherapy outcomes.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors [dataset 1]

summary: Monocyte–derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs’ survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.

overall_design:
Mouse: Gene expression and chromatin accessibility (scRNA-seq, n = 3; scATAC-seq, n = 4) of myeloid cells from lung, blood and bone marrow of naive and KP tumor-bearing mice.
Human: Gene expression and chromatin accessibility (multiome, n = 14; scATAC-seq, n = 27) of CD45-positive cells from PBMC, Tumor and Adjacent Normal tissues of 14 patients with non-small cell lung cancer (NSCLC).
Mouse: Chromatin accessibility (scATAC-seq, n = 4) from lung and bone marrow of naïve or KP tumor-bearing mice.

first: Samarth

last: Hegde

first: Miriam

last: Merad


title: The mitotic STAG3–cohesin complex shapes male germline nucleome

city: Kyoto

first: Yukihiro

last: Yabuta

state: Kyoto

address: Yoshida-Konoe-cho, Sakyo-ku

department: Anatomy and Cell Biology

country: Japan

institute: Kyoto University, Graduate school of medicine

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


title: Evaluation of Vitamin D and Doxercalciferol Effect on Uterine Fibroid Growth

status: Public on Jul 02 2025

city: Valencia

first: Ana

last: Corachán

state: València

address: Avenida Fernando Abril Martorell, 106, torreA, Planta 7

country: Spain

institute: IVIRMA Global Research Alliance, IVI Foundation, IIS La Fe

summary: Uterine fibroids (UF) are the most common pelvic tumor in women of reproductive age. Despite its high prevalence, there is an unmet need in the field for a non-hormonal fertility-friendly anti-fibroid treatment. Vitamin D deficiency has been linked to a higher risk of UF, and its efficiency as a treatment to reduce UF size has been demonstrated in vitro and in vivo. However, long-term vitamin d treatments could induce hypercalcemia, and vitamin D analogs have been proposed as an alternative since they show less calcemic activity. Our study aims to describe the signaling pathways and molecular mechanisms by which Vitamin D (VD3) and Doxercalciferol (a Vitamin D analog) (DCL) reduces UF size in a UF patient-derived xenograft (PDX).

overall_design: MED12-mutant human uterine fibroids (UF) were collected from African American women undergoing hysterectomy or myomectomy for symptomatic UF (n=10). Female NOD-SCID mice (n=14) were used to generate the PDX mouse model. Mice were hormonally supplemented with 60-day release pellets with 17ß-estradiol (0.2 mg) and progesterone (50 mg). One week after the xenograft surgery, animals were treated for 6 weeks with the bioactive form of Vitamin D3 (VD3), 1α,25(OH)2D3 and the synthetic Vitamin D2 analog Doxercalciferol (DCL). According to the treatment two different studies were conducted: 1) VD3 0.5 µg/kg/day (n=3) and 2) DCL 0.3 µg/kg/day (n=4). Each study had her own control group, in which animals were treated with the corresponding drug vehicle. At the end of the treatment, animals were euthanized and UF xenografts were collected. Each study had her own control group, in which animals were treated with the corresponding drug vehicle.

first: Maria

middle: V

last: Bariani

first: Mohamed

last: Ali

first: Qiwei

last: Yang

first: Hortensia

last: Ferrero

first: Ayman

last: Al-Hendy


title: MTA1 Rewires Prostate Cancer Transcriptomes: Direct RNA Interactions Govern Oncogenic Gene Expression and Splice Variant Networks [RNA-Seq]

status: Public on Jul 01 2025

city: Hefei

first: Lei

last: Chen

address: No. 678, Furong Road, Shushan District

institute: The Second Affiliated Hospital of Anhui Medical University

summary: MTA1, a well-characterized epigenetic modifier, plays pivotal roles in cancer progression. However, its involvement in RNA-mediated regulatory mechanisms remains poorly understood. This study unveils MTA1’s dual functionality as a chromatin remodeler and RNA-binding protein (RBP) in prostate cancer (PCa) pathogenesis. By integrating RNA sequencing (RNA-seq) and formaldehyde-crosslinking RNA immunoprecipitation sequencing (fRIP-seq) in PC-3 cells, we demonstrate that MTA1 knockdown dysregulates 1,248 genes and modulates 2,367 alternative splicing events (ASEs). Functional annotation links MTA1-associated differentially expressed genes (DEGs) to extracellular matrix (ECM) remodeling, PI3K-Akt signaling, and hypoxia responses, while ASEs implicate spliceosome activity and RNA processing pathways. fRIP-seq identifies direct MTA1-bound RNAs enriched with GC-rich motifs, with integrative analyses revealing significant overlaps between MTA1 RNA targets and DEGs/ASEs. Our findings establish MTA1 as a multifunctional RBP bridging transcriptional and post-transcriptional networks, offering novel mechanistic insights into PCa progression.

overall_design: This study utilized prostate cancer PC-3 cells as the model system to systematically investigate the role of MTA1 in transcriptional and post-transcriptional regulation through MTA1 knockdown (KD) combined with RNA-seq and fRIP-seq analyses. RNA-seq identified 1,248 differentially expressed genes (DEGs) and 2,367 alternative splicing events (ASEs). Functional analysis revealed that DEGs were primarily enriched in ECM remodeling, PI3K-Akt signaling, and hypoxia response, while ASEs were associated with spliceosome activity and RNA processing. fRIP-seq identified MTA1 directly bound RNAs, which exhibited a preference for GC-rich motifs, and integrative analysis demonstrated significant overlap between MTA1 RNA targets and DEGs/ASEs. These findings confirm MTA1's dual functionality as an RNA-binding protein (RBP) in transcriptional and splicing regulation, providing novel mechanistic insights into prostate cancer progression.

first: Guanlin

last: Qu

first: Fuhao

last: Li

first: Bin

last: Wu

first: Enlai

first: Shen

last: Xu


title: Stage-specific extracellular vesicle cargo from Schwann cells orchestrates peripheral nerve regeneration

city: Cincinnati

first: Leyla

last: Esfandiari

state: OH

address: 2600 Clifton Ave

institute: University of Cincinnati

type: Non-coding RNA profiling by high throughput sequencing

summary: Schwann cells (SCs) play a critical role in peripheral nerve regeneration, undergoing dynamic phenotype transitioning from myelinating to repair stages following injury. While SC-derived extracellular vesicles (SC-EVs) have emerged as key mediators of intercellular communication during nerve repair, their stage-specific molecular cargo and functional roles remained incomplete understood. Here, we delineate protein, microRNA   and lncRNA landscapes of SC-EVs across distinct differentiation stages, including immature, myelinating, and repair phenotypes, using an in vitro model of primary rat SCs. We show that myelinating SC-EVs are enriched with reprogramming factor SOX2 and neurotrophin receptor p75NTR, while repair SC-EVs carry distinct microRNAs predicted to modulate genes involved in myelin ensheathment, neuronal differentiation and neurogenesis.   Moreover, repair SC-EVs contain long non-coding RNAs (lncRNAs) that may regulate miRNA activity. These findings reveal a novel mechanism by which SC-EVs orchestrate neuronal regeneration through stage-specific molecular cargo, and establishes a foundational model for investigating SC plasticity in peripheral nerve repair

overall_design: Schematic of the in vitro differentiation model used to induce Schwann cells (SCs) to induce myelination, followed by reversion to a repair phenotype. Rat primary SCs were treated with 1 mM dbcAMP in rat SC basal media for 72 h to induce differentiation into myelinating SCs, followed by dbcAMP withdrawal to reprogram into repair SCs. Conditioned culture media was used to extract small extracellular vesicles. Total RNA was extracted from cell lysates and EV samples and then sequenced for mRNA, miRNA, and lncRNA.

first: Manju

last: Sharma

first: Supasek

last: Kongsomros

first: Maulee

last: Sheth

first: Somchai

last: Chutipongtanate


title: The mitotic STAG3–cohesin complex shapes male germline nucleome [SC3-seq]

first: Yukihiro

last: Yabuta

summary: Germ cells are unique in that they tailor chromatin toward generating totipotency. Accordingly, mammalian spermatogonia, including spermatogonial stem cells (SSCs) which constitute the source for male gametes, acquire distinctive chromatin organization with weak insulation, but the underlying mechanism remains unknown.  Here, we show that STAG3, this far known to exclusively form meiotic cohesins, generates a mitotic cohesin for male germline nucleome programming in mice.  Due to its shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs), rewires enhancer–promoter and Polycomb-mediated repressive interactions, and facilitates finer and more strengthened compartments, establishing a distinctive spermatogonial nucleome.  Moreover, in the absence of STAG3–cohesin, SSCs show an impaired differentiation priming for spermatogenesis.  Mitotic STAG3–cohesin is also expressed in human B cells and their malignant variations, promoting their propagation.  Our findings on mitotic STAG3–cohesin elucidate a principle of male germline nucleome programming, demonstrate an unexpected mitotic role for STAG3 and might potentially improve understanding of human malignancies.

overall_design: SC3-seq (Nakamura et al., 2015) for STAG3-cohesin characterization in WT and Stag3 KO GSCs and female and male germ cells in vivo.

first: Masahiro

last: Nagano

first: Bo

last: Hu

first: Kosuke

last: Ogata

first: Fumiya

last: Umemura

first: Yukiko

last: Ishikura

first: Shinnosuke

last: Suzuki

first: Christos

middle: C

last: Katsifis

first: Masanori

last: Yoshinaga

first: Gabriele

last: Litos

first: Kota

last: Nagasaka

first: Wen

last: Tang

first: Yoshiaki

last: Nosaka

first: Hiromichi

last: Sasada

first: Hanbo

last: Wang

first: Daichi

last: Kondo

first: Yoshitaka

last: Kato

first: Ken

last: Mizuta

first: Hiroshi

last: Ohta

first: Francisca

middle: N

last: de Luna Vitorino

last: Arima

first: Takafumi

last: Ichikawa

first: Michele

last: Gabriele

first: Jacek

last: Majewski

first: Benjamin

last: Garcia

first: Osamu

last: Takeuchi

first: Shosei

last: Yoshida

first: Anders

last: Hansen

first: Jan-Michael

last: Peters

first: Yasushi

last: Ishihama

first: Mitinori

last: Saitou


title: MTA1 Rewires Prostate Cancer Transcriptomes: Direct RNA Interactions Govern Oncogenic Gene Expression and Splice Variant Networks [RIP-Seq]

first: Lei

last: Chen

first: Guanlin

last: Qu

first: Fuhao

last: Li

first: Bin

last: Wu

first: Enlai

first: Shen

last: Xu


title: Genome-wide maps of chromatin state in MHCC97L cells

city: Shanghai

first: Xianghuo

last: He

address: No 270, Dong An Road

institute: Fudan University

summary: We report the application of chromatin immunoprecipitation sequencing (ChIPseq) for high-throughput profiling of histone modifications in MHCC97L cells.

overall_design: ChIP-seq were performed with antibodies against acetylated H3K27 (H3K27ac), H3K4me1, and H3K4me3 to detect the genome-wide maps of chromatin state in HCC cells.

first: Zhiao


title: Foxc1 ChIP-seq in Gli2-mGFP NIH3T3 cells stably expressing Foxc1 ORF

status: Public on Jun 27 2025

city: Edmonton

first: Serhiy

last: Havrylov

state: Alberta

address: 8-29 Medical Sciences Building

department: Medical Genetics

country: Canada

institute: University of Alberta

summary: To interrogate occupany sites of Foxc1 transcription factor whole genome ChIP-sequencing was performed on Gli2-mGFP NIH3T3 reporter cells stably expressing Foxc1, using different anti-Foxc1 antibodies.

overall_design: Two independent Foxc1 antibodies (ab1, ab2) were used, together with an isotype-matched control immunoglobulin as control for Foxc1 peak specificity.

first: Ordan

last: Lehmann


title: Gene expression changes associted with overexpression of Foxc1 transcription factor in NIH3T3 fibroblasts

summary: To identify pathways transcriptionally controlled by Foxc1, NIH3T3 fibroblasts stably overexpressing Foxc1 ORF, or an empty retroviral vector control, were subjected to RNA-sequencing.

overall_design: RNA-seq profiling of NIH3T3 fibroblasts stably expressing muouse Foxc1 ORF or an empty pLXSH vectr control.


title: A Transcriptomics-Based Computational Drug Repositioning Pipeline Identifies Simvastatin And Primaquine As Therapeutics For Endometriosis

status: Public on Jun 25 2025

city: San Francisco

first: Marina

last: Sirota

institute: UCSF

summary: Endometriosis is a disease with limited medical treatment options and a strong need for new therapeutic strategies. We previously applied a transcriptomics-based computational drug repositioning pipeline to publicly available bulk transcriptomic data to identify potential therapeutics for endometriosis. The drug candidates identified in silico includes fenoprofen, primaquine, and simvastatin. Validation of these drugs in our rat endometrial model determined that they significantly reduced endometriosis-associated vaginal hyperalgesia, a surrogate marker for endometriosis-related pain. The signatures of DEGs from uteri and lesions demonstrated reversal of the endometriosis disease signature with simvastatin and primaquine treatment.

overall_design: RNA profiling on a rat model of endometriosis with a WT (no endo+no drug) group and five treatment groups: vehicle, fenoprofen, primaquine, simvastatin, and ibuprofen (positive control). Each group included six rats.

first: Tomiko

middle: T

last: Oskotsky

first: Xinyu

last: Tang

first: Erin

last: Arthurs

first: Arpita

last: Govil

first: Linda

last: Giudice

first: Stacy

middle: L

last: McAllister


title: Age-dependent Transcriptional and Circuit Alterations in the brain Underlie Post-Anesthesia Neurobehavioral Dysfunction

city: Baltimore

first: Hangnoh

last: Lee

state: MD

address: 670 W Baltimore St

institute: University of Maryland School of Medicine

summary: With rising life expectancy, an increasing number of elderly individuals are undergoing surgery, highlighting the need to understand postoperative neurological complications. General anesthesia (GA) has been linked to olfactory dysfunction (OD) and cognitive impairment after surgery, but the underlying mechanisms remain poorly defined. In this study, 20-month-old male C57BL/6 mice underwent laparotomy followed by 2 hours of isoflurane exposure to examine the molecular effects of GA and surgery up to 5 weeks post-intervention using bulk RNA sequencing (RNAseq). Transcriptomic analysis of the olfactory bulb (OB) at 1 day post-GA/operation revealed upregulation of ubiquitin-related proteins and catabolic pathways in aged mice compared to shams. In contrast, RNAseq of the hippocampus (HI) at 5 weeks post-GA/OP showed broader molecular changes, coinciding with delayed cognitive decline. Compared to young adults, aged GA/OP mice exhibited elevated expression of innate immune genes and reduced neurogenesis in the OB, along with increased gliogenesis and impaired RNA splicing in the HI.

overall_design: RNA-Seq gene expression profiling was performed on mice aged 10–12 weeks or approximately 20 months, subjected to either sham treatment or GA (isoflurane) exposure followed by surgery (midline laparotomy). Olfactory bulb and hippocampus tissues were collected at 24 hours or 5 weeks post-GA/operation. Transcriptomic differences between GA/OP and Sham mice were analyzed.

first: Yun

first: Junfang


title: Role of ATF4 in regulation of kidney gene expressions, signaling pathways and functions

first: Genomics-core-facility

last: WCM

address: 1300 York Ave.

institute: Weill Cornell Medicine


title: Inactivated Rothia nasimurium promotes a persistent antiviral immune status in porcine alveolar macrophages

city: Bellaterra, Catalonia

first: Jordi

last: Argilaguet

address: Campus de la Universitat Autònoma de Barcelona (UAB)

department: Sanitat animal

institute: IRTA-CReSA

summary: Globalization has increased in the incidence of infectious diseases in livestock, further aggravated by the reduction of antibiotic consumption. To minimise the resulting economic consequences to the meat production industry, as well as the higher risk of zoonotic events, immunostimulants have risen as a potential strategy to enhance animal resilience to diseases. The capability of bacterial-based immunostimulants to modulate innate immune cells functionality makes them cost-effective candidates to be used in livestock, whether as vaccine adjuvants, as antimicrobials, or as preventive immunostimulators inducing long-term innate immune memory. Here we characterized in vitro the immunostimulatory properties of a strain of Rothia nasimurium isolated from warthog fecal microbiota. Stimulation with heat-inactivated bacteria induced cytokine production by porcine immune cells, and a robust innate immune transcriptomic signature in porcine alveolar macrophages. Interestingly, the bacteria induced inflammasome activation and IL1b production, thus confirming its proinflammatory properties, and suggesting its potential as vaccine adjuvant. Importantly, this immunostimulatory status functionally resulted in an antimicrobial state, hampering the replication levels of two major porcine viral pathogens: the porcine reproductive and respiratory syndrome virus (PRRSV) and the African swine fever virus (ASFV). Moreover, alveolar macrophages showed an enhanced cytokine response upon ASFV infection several days after heat-inactivated bacteria stimulation, suggesting the induction of an innate immune memory phenotype. This nonspecific response resulted in a significant reduction of ASFV replication kinetics, demonstrating the capacity of the bacteria to induce a more resistant state in macrophages against a highly lethal virus infection. Altogether, these results demonstrate the immunostimulatory capability of heat-inactivated Rothia nasimurium in porcine macrophages, showing potential to enhance animal resilience to diseases through the modulation of innate immune cells responsiveness to infections.

overall_design: Four lots of PAMs were seeded at 5x10^6 cells/well in a 24-well flat-bottom plate with RPMI supplemented with 10% FCS, 1% of P/S, 1% of L-glutamine, and 0.5% of nystatin, and left overnight at 37ºC and 5% CO2. Cells were then stimulated for 6 or 24 hours with LPS (tlrl-eblps InvivoGen) at 10 ug/ml, Pam3CKS (InvivoGen tlrl-pm2s-1) at 10 ug/ml, or heat-inactivated Rothia nasimurium (HI-Ro) at MOI 50. Non-stimulated cells were used as a reference.

first: Aida

last: Tort-Miró

first: Uxia

last: Alonso

first: Beatriz

last: Martín-Mur

first: Anna

last: Cardona-Coma

first: Jordana

last: Muñoz-Basagoiti

first: Yan

last: Zeng

first: David

last: Marín-Moraleda

first: Enrique

last: Ezcurra

first: Sergio

last: Montaner

first: Maria Jesus

last: Navas

first: Marta

last: Muñoz

first: Paula

last: Monleón

first: Esmeralda

last: Cano

first: Carles

last: Vilalta

first: Marc

last: Caballé

first: Lourdes

last: Criado

first: Karl

last: Kochanowski

first: Francesc

last: Accensi

first: Virginia

last: Aragón

first: Flor

last: Correa

last: Esteve-Codina

first: Fernando

last: Rodríguez


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

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: BET bromodomain inhibitors attenuate transcription of a subset of IL-1-induced NF-κB target genes that promote inflammation in β-cells

city: Milwaukee

first: Joshua

last: Nord

state: WI

address: 8701 W Watertown Plank Rd

institute: Medical College of Wisconsin

summary: Cytokine-stimulated transcription of NF-κB target genes is linked to the development of multiple inflammatory and autoimmune diseases. Inhibitors of bromodomain and extraterminal domain (BET) epigenetic reader proteins attenuate inflammatory gene transcription and delay the onset of several inflammatory diseases, including autoimmune diabetes. Our previous studies showed that BET bromodomain inhibitors disrupt the interaction between BET family member BRD4 and NF-κB transcription factor p65 in β-cells, thus attenuating cytokine-stimulated NF-κB-dependent gene and functional changes. However, the role of NF-κB in developing inflammatory disease is controversial, as NF-κB inhibition can promote disease progression in some contexts. NF-κB target genes play both physiological and pathophysiological roles in regulating the cellular response to cytokines. Here, using cytokine-stimulated pancreatic β-cells as an inflammatory disease model, we show that NF-κB-dependent gene products that participate in inflammation are sensitive to BET bromodomain inhibition. In contrast, gene products that maintain cellular homeostasis or protect β-cells from stressors are largely insensitive to BET bromodomain inhibition. These studies define a novel and selective role for BET bromodomain-containing proteins in regulating inflammatory gene activation.

overall_design: INS 832/13 rat insulinoma cells treated with BET bromodomain inhibitor (+)-JQ1 (dissolved in DMSO). DMSO was used as a control.

first: Savannah

last: Makowski

first: Paul

middle: F

last: Sidlowski

first: Karina

last: Bursch

last: Corbett

first: Brian

last: Smith


title: Role of ATF4 in regulation of kidney gene expressions, signaling pathways and functions [mouse]

first: Genomics-core-facility

last: WCM

summary: Activating transcription factor 4 (ATF4) is a transcription factor that mediates the response to stress at the cellular, tissue, and organism level. We deleted the gene encoding ATF4 in the kidney proximal tubules of the wild type (WT) and TRACK (TRAnsgenic model of Cancer of the Kidney (TRACK)) mice by using a temporal and cell type-specific approach. We show that ATF4 plays a major role in regulating the transcriptome and proteome, which, in turn, influences the metabolome and kidney functions. ATF4 deletion changed transcripts of some transporters responsible for nutrient uptake and waste excretion. It modulates metabolisms of fatty acid and glucose in the mouse model of ccRCC. It also changes metabolism in RCC4 cells. These data indicate that ATF4 plays an important role in regulation of kidney functions.

overall_design: RNA seq profiling of cortices from mice of wild type, ATF4 KO, TRACK and TRACK-ATF4, profiing of parental RCC4 cells and RCC4 ATF4 KO cells.

first: Lorraine

last: Gudas

first: Yuling

last: Chi

first: Eduardo Mere

last: Del Aguila


title: Injury-induced niche factors Cxcl12 and Shh/Ihh coordinate suture stem cell activation during calvarial bone regeneration

status: Public on Jun 23 2025

city: Boston

first: Yuchen

last: Liu

state: Massachusetts

address: 188 Longwood Avenue, REB 514B

institute: Harvard school of dental medicine

summary: Suture stem cells (SuSCs) are important for homeostasis and regeneration of cranial bone and can be used as a model to understand stem cell regulation for bone regeneration at a distance. Using a mouse cranial bone injury model, we identified the chemokine Cxcl12 and the Hedgehog family ligands Shh and Ihh as injury-induced interacting niche factors that coordinately regulate Gli1+ SuSC expansion, directional migration,and osteoblastic differentiation. Cxcl12 increased in the early inflammatory phase after injury, and Cxcl12-mediated activation of its cognate receptor, Cxcr4, in Gli1+ SuSCs promoted bone regeneration by stimulating SuSC proliferation and migration. Cxcl12-Cxcr4 signaling induced Shh and Ihh expression, which promoted Gli1+ SuSC proliferation and osteoblastic differentiation.

overall_design: RNA-seq was profiled of the cranial suture tissues, including coronal, sagittal, and lambdoid sutures of new-born wildtype mouse pups.

first: Takehito

last: Ochi

first: Bo

last: Li

first: Yingzi

last: Yang


title: Role of ATF4 in regulation of kidney gene expressions, signaling pathways and functions [human RCC4]


title: Spatial transcriptomics from paired pancreas and associated draining lymph nodes reveals a lymphotoxin-beta signature in human type 1 diabetes

city: Gainesville

first: Miguel

last: Medina-Serpas

state: FL

address: 1275 Center Dr

institute: University of Florida

summary: This study explores the inflammatory response involved in type 1 diabetes (T1D) using multi-cell resolution spatial transcriptomics (ST) to assay paired pancreas and pancreatic lymph node (pLN) samples from human donors across the natural history of T1D. Integration of ST with public single-cell RNA sequencing data enabled interrogation of transcriptional alterations in T1D across both tissues at the cellular scale. In the T1D pancreas, we identified global upregulation of inflammation-associated transcripts, including multiple regenerating islet-derived (REG) family genes, complement factor 3 (C3), SOD2, and OLFM4, and highlighted cellular candidates potentially contributing to these signatures. Within the T1D pLN, we observed spatially restricted upregulation of lymphotoxin- (LTB) alongside follicular dendritic cell (FDC)-associated transcripts including FDCSP, CLU, and FCER2. Collectively, these findings highlight a distinct inflammation signature in the pancreas and evidence of enhanced follicular activity in the associated pLN.

overall_design: Spatial transcriptomics using the 10x Genomics Visium spatial gene expression assay performed on human donor pancreas and associated pancreatic lymph node sections from non-diabeitc controls, non-diabetic islet autoantibody positive donors at high risk, and T1D donors.

first: Todd

last: Brusko


title: Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromes [ChIP-Seq]

city: Bronx

first: Kith

last: Pradhan

state: ny

address: 1300 Morris Park Ave

institute: Einstein College of Medicine

summary: Anemia is the primary clinical manifestation of myelodysplastic syndromes (MDS), but the molecular pathogenesis of ineffective erythropoiesis remains incompletely understood. Luspatercept, an activin receptor 2B (ACVRIIB-Fc) ligand trap, has been approved to treat anemia, however its molecular mechanism of action is unclear. We found that the ACVR2B, its ligand GDF11, and effector, SMAD2, are upregulated in MDS patient samples. GDF11 inhibited human erythropoiesis in vitro and caused anemia in zebrafish, effects that were abrogated by luspatercept. Upon GDF11 stimulation of human erythroid progenitors, SMAD2 binding occurred in the erythroid regulatory regions, including at GATA1 intron. Intronic SMAD2 binding led to skipping of exon 2 of GATA1, resulting in a shorter, hypomorphic isoform (GATA1s). CRISPR deletion of the SMAD2 binding intronic region decreased GATA1s production upon GDF11 stimulation. Expression of gata1s in a mouse model led to anemia, rescued by a murine ActRIIB-Fc (RAP-536). Finally, RNA-seq analysis of samples from the Phase 3 MEDALIST trial revealed that responders to Luspatercept had a higher proportion of GATA1s compared to non-responders. Moreover, the increase RBCs post-treatment was linked to a relative decrease in GATA1s isoform. Our study indicates that GDF11-mediated SMAD2 activation results in an increase in functionally impaired GATA1 isoforms, consequently contributing to anemia and influencing responses to Luspatercept in MDS.

overall_design: A total of 25 million cells were treated with GDF11 and TGF-β1. After a 2-hour treatment, the cells were pelleted at 350 x g for 15 minutes at 4°C. They were then washed once with ice-cold PBS. The following steps were followed using the Diagenode HighCell ChIP Kit (Cat# C01010060), according to the manufacturer's protocol.

first: Srinivas

last: Aluri

first: Amit

last: Verma


title: RNF126 Promotes Endoplasmic Reticulum Stress in Fetal Growth Restriction via Ubiquitination-Mediated Degradation of the MYH9/MYH10 Complex

status: Public on Jun 20 2025

city: Guangzhou

first: Jing

state: Guangdong

address: Jingxi Street

department: Department of Obstetrics and Gynecology

institute: Southern Medical University Nanfang Hospital

summary: Fetal growth restriction (FGR) stands as a prominent cause of neonatal morbidity and mortality, yet its underlying mechanisms remain elusive. Through a multi-omics analysis of the human placentas, including quantitative proteomics and ubiquitination-modified proteomics, our team find that the E3 ligase Ring finger protein 126 (RNF126) might be a potentially pivotal protein in the development of FGR. Here, we have discovered that RNF126 can induce endoplasmic reticulum stress (ERS) in placental trophoblasts through RNA sequencing, leading to an increase in apoptosis rates. Subsequent studies have confirmed that RNF126 promotes the degradation of the MYH9/MYH10 complex via the ubiquitin-proteasome pathway, thereby contributing to ERS and inducing trophoblast dysfunction. Meanwhile, Our RNF126 placenta-specific knockout mouse model (cKO) validates these findings in vivo. These events significantly contribute to the occurrence and progression of FGR. This study provides new insights and highlights the promising potential of RNF126 as a therapeutic target for FGR treatment.

overall_design: We conducted RNA-seq on BeWo cells that were stably overexpressed with empty vector (OE-NC) or RNF126 (OE-RNF126) using lentiviruses. n = 3 biologically independent experiments.

first: Lilin

last: Lu

first: Xiaomei

last: Ye

first: Jiawen

last: Lan

first: Shuxiu

last: Xu

first: Manyu

last: Cheng

first: Chenlin

last: Lv

first: Jun

last: Zhou


title: Genome reorganization and its functional impact during breast cancer progression [Micro-C]

status: Public on Jun 16 2025

city: Bethesda

first: Kathleen

middle: Shaindel Metz

last: Reed

address: 41 Medlars Dr, B507

department: Genetics and Molecular Biology

institute: National Cancer Institute, NIH

summary: We used Micro-C to explore conformational changes in the cancer genome, using the MCF10 cell line as a model for breast cancer progression. We have generated 5kb-resolution maps in normal (MCF10A), pre-malignant (MCF10AT1), and metastatic (MCF10CA1a) breast cancer cell lines, and aim to identify differential enhancer-promoter interactions between the different stages of cancer progression that may contribute to oncogenesis.

overall_design: Micro-C in MCF10A, MCF10AT1, and MCF10CA1a cell lines (2 biological replicates per cell line, 4 technical replicates per biological rep). Micro-C was conducted by Cantata Bio.

last: Metz Reed

first: Tom

last: Misteli

first: Andrew

last: Fritz

first: Haley

last: Greenyer

first: Seth

last: Frietze

first: Janet

last: Stein

first: Gary


title: Inactivation of histone chaperone HIRA unmasks a link between normal embryonic development of melanoblasts and maintenance of adult melanocyte stem cells

status: Public on Jun 13 2025

city: La Jolla

first: Peter

middle: D.

last: Adams

state: CA

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program

institute: Sanford Burnham Prebys Medical Discovery Institute

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

overall_design: Refer to individual Series


title: Arabidopsis chromatin remodeler SPLAYED is required for abscisic acid-mediated post-germination growth arrest

status: Public on Jun 12 2025

first: Po-Kai

last: Hsu

address: 9500 Gilman Dr

department: Cell and Developmental Biology

institute: UC San Diego

summary: The phytohormone abscisic acid (ABA) promotes seed dormancy, inhibition of seed germination, and post-germination growth arrest. It remains unclear how chromatin remodeling influences ABA responses during early seedling establishment. In this study, an artificial microRNA targeting two Sucrose non-fermenting 2 (SNF2)-family chromatin remodeling ATPases, SPLAYED (SYD) and PHOTOPERIOD-INDEPENDENT EARLY FLOWERING1 (PIE1), was identified through unbiased forward genetic screening of artificial microRNA (amiRNA)-expressing pooled seed libraries exhibiting ABA insensitivity during the seed-to-seedling transition. T-DNA insertional mutants of syd and pie1, along with amiRNA-expressing knockdown lines amiR-SYD and amiR-PIE1, confirmed that SYD is required for ABA inhibition of post-germination growth. Transcriptomic analyses revealed that, under ABA treatment, amiR-SYD mutant seeds exhibited increased expression of the ABA catabolism gene CYP707A3 and the gibberellin (GA) biosynthesis genes GA20OX2, GA20OX3, GA3OX1, GA3OX2, and GA3OX4. Concurrently, the ABA-responsive genes KIN1 and EM6 were less strongly induced, whereas the GA-responsive genes GASA4 and GASA6 were more strongly induced. The ABA hyposensitivity observed in amiR-SYD mutants was reversed by treatment with uniconazole, an inhibitor of ABA catabolism and GA biosynthesis. These findings suggest that the SYD-associated chromatin remodeling complex positively regulates ABA-mediated post-germination growth arrest by modulating the balance between ABA and GA responses, in contrast to its close homolog BRAHMA (BRM), which negatively regulates ABA responses through an ABI5-mediated checkpoint.

overall_design: Expression profiling of amiR-HsMYO control and amiR-SYD seeds germinated on ½ MS medium with either 0.002% EtOH (control) or 2 μM (±)-ABA under long-day conditions for 24 h. Please see the associated samples for the experimental design.

middle: K

first: Julian

middle: I

last: Schroeder


title: Functional relevance of naturally occurring single nucleotide polymorphisms in bovine leukemia virus-encoded microRNAs.

status: Public on Jun 15 2025

city: Pulawy

first: Aneta

last: Pluta

state: Lublin

address: Av Partyzantow 57

department: Department of Virology and Viral Animal Diseases

institute: National Veterinary Research Institute

summary:
Background: Bovine leukemia virus (BLV) microRNAs (miRNAs) contribute to viral latency and immune evasion. Naturally occurring single-nucleotide polymorphisms (SNPs) within the BLV miRNA cluster have been associated with persistent lymphocytosis in cattle, yet their functional impact remains unclear.
Aims: This study aims to (1) evaluate how SNPs in BLV miRNAs affect miRNA biogenesis and mature miRNA levels; (2) determine whether specific SNPs alter miRNA–mRNA interactions and identify affected targets; and (3) characterize transcriptomic changes induced by reference versus SNP-bearing miRNAs.
Methods: BLV miRNA loci were PCR-amplified and sequenced from 53 blood samples of infected cattle. Both reference and SNP-containing precursors were cloned into expression vectors and co-transfected with an miRNA-deficient BLV clone into HEK293T cells. Mature miRNA levels were quantified via stem-loop RT-qPCR. Computational target prediction (miRanda) validated changes in mRNA targeting. Gene-expression effects were assessed using Agilent microarrays, with selected findings confirmed by RT-qPCR and subjected to pathway enrichment analysis (IPA).
Significance: This work will elucidate how BLV miRNA polymorphisms modify miRNA maturation and target recognition, reshape host gene networks, and contribute to viral persistence and immune modulation.

overall_design: Fifty‐three blood samples were collected from cattle naturally infected with BLV. BLV miRNA coding regions were PCR‐amplified and sequenced to identify isolates carrying either the reference miRNA sequence or specific SNP variants. Selected miRNA precursors (both reference and SNP‐containing) were cloned into expression vectors and co‐transfected with an miRNA‐deficient BLV clone into HEK293T cells in three independent biological replicates. Mature miRNA levels were quantified by RT‐qPCR. For transcriptomic profiling, total RNA from the three independent transfections for selected miRNA variants (reference, V29, V90) and from two control groups (empty vector ± BLV) were pooled by group and analyzed using Agilent two‐color microarrays in six technical replicates. Differentially expressed genes were validated by RT‐qPCR and then subjected to pathway enrichment analysis (IPA).

first: Kerstin

last: Skovgaard


title: Human airway submucosal gland organoids to study respiratory inflammation and infection [bulk RNA-seq]

city: Utrecht

first: Carla

last: Pou Casellas

address: Uppsalalaan 8

country: Netherlands

institute: Hubrecht Institute

summary: The human airway lining consists of two physiologically distinct compartments: the surface airway epithelium (SAE) and the submucosal glands (SMGs). Despite their critical role, SMGs have remained largely overlooked in airway in vitro modeling of respiratory inflammation and infection. In this study, we leverage long-term cultured organoids derived separately from SAE and SMG to investigate their unique physiological characteristics. Single-cell RNA sequencing (scRNA-seq) analysis confirms that these organoid models accurately replicate the cellular heterogeneity inherent to each tissue type. Specifically, SMG organoids are enriched in MUC5B-producing mucous cells and generate alpha-Smooth Muscle Actin (αSMA)-expressing myoepithelial cells. We identify ANPEP/CD13 as a specific cell surface marker for SMG secretory cells. Exposure to cytokines elicits distinct transcriptomic responses in SMG secretory cells, providing insights into the cellular mechanisms underpinning inflammatory pathogenesis. Infection assays with human alpha-coronavirus 229E (HCoV-229E) reveal a selective vulnerability of CD13-positive secretory cells within SMG organoids, triggering a specific unfolded protein response associated with endoplasmic reticulum (ER) stress. These findings broaden the utility of airway organoids for precision modeling of respiratory (patho-)physiology

overall_design: Bulk RNA sequencing of CD13- and CD13+ cells from human primary tissue-derived SMG organoids (3 different donors) unexposed or exposed to hCoV-229E-EGFP

first: Lin

last: Lin

first: Hans

last: Clevers


title: Cardiomyocyte OTUD1 drives diabetic cardiomyopathy via directly deubiquitinating AMPKα2 to inhibit AMPK activity and induce mitochondrial dysfunction

status: Public on Jun 11 2025

city: hangzhou city

first: liu

middle: guo

last: xuan

address: No. 182 Tianmushan Road, Hangzhou City, Zhejiang Province

institute: Hangzhou Medical College

summary: To analyze the mRNA profile of DUBs in diabetic heart, we performed a scRNA-seq of  heart cells from the wild type (WT) mice and db/db mice, a typical T2DM model mouse.

overall_design: wild type (WT) mouse (n=1) and  typical T2DM model mouse (n=1)

first: Guang

last: Liang

first: Xue

last: Han


title: Single cell RNA Sequencing of murine tdTomato positive skin cells with or without HIRA knockout


title: Inactivation of histone chaperone HIRA unmasks a link between normal embryonic development of melanoblasts and maintenance of adult melanocyte stem cells (ATAC-Seq)

summary: Evidence indicates that the integrity of in utero embryonic development can influence late life healthy or unhealthy aging. However, specific links between embryonic development and late life aging are not well defined. Histone chaperone HIRA is thought to play a role in both early development and aging. Here, we explore the relationship between HIRA’s roles in development and aging by comparing lineage-specific constitutive and conditional Hira knock out in the murine pigmentary system, with constitutive knock out initiated during embryogenesis and conditional knock out in young adults. Embryonic Hira knockout leads to reduced melanoblast numbers during embryogenesis but wild type numbers of differentiated melanocytes at birth, normally functioning juvenile and young adult melanocyte stem cells (McSCs), and only a very mildly hypopigmented first hair coat. However, on closer analysis of these mice, Hira knockout melanocytic cells of newborn mice exhibit molecular markers characteristic of cell aging and proliferative deficits. As they age, mice with Hira knock out initiated during embryogenesis display marked defects in McSC maintenance and premature hair graying. Importantly, these defects are only observed when HIRA is inactivated during embryogenesis, but not in young adults. This genetic model shows that HIRA function during early development lays a foundation for subsequent maintenance of adult tissue specific stem cells during aging.

overall_design: ATAC sequencing was used to study the chromatin accessibility changes of HIRA KD on in-vitro melb-a cells. We used two control lenti- shRNAs (shLuciferase, shScramble), as well as two lenti- shRNAs to knock down HIRA (shHIRA I, shHIRA II). Chromatin accessibility analysis was performed using data obtained from bulk-ATAC seq of 4 samples.

first: Rouven

last: Arnold

first: Rabi

last: Murad

first: Farah

last: Jaber-Hijazi

middle: D


title: Single cell RNA Sequencing of murine tdTomato positive skin cells with or without HIRA knockout [dataset 2]

summary:
Skin samples from wild type or HIRA knockout mouse embryos were dissociated to give cellular suspensions, then single cell RNA sequencing was performed using the 10X platform.
Method: Cellular suspensions of skin cells from wild type and HIRA knockout mice were prepared, then sequencing was performed using the Chromium 10X system. Data were then processed using Cellranger version 2.2.0.

overall_design: Isolated single cells from E15.5 skin from wild type and HIRA knockout mice were sequenced using the 10X Genomics platform.

first: Kathryn

last: Gilroy


title: Inactivation of histone chaperone HIRA unmasks a link between normal embryonic development of melanoblasts and maintenance of adult melanocyte stem cells (RNA-Seq)

overall_design: RNA sequencing was used to study the transcriptomic changes of HIRA KD on in-vitro melb-a cells. We used parental non-transduced cells, two control lenti- shRNAs (shLuciferase, shScramble), as well as two lenti- shRNAs to knock down HIRA (shHIRA I, shHIRA II). Gene expression analysis was performed using data obtained from bulk-RNA seq of 20 samples (4 independent replicates per experimental group).

first: Arnold

last: Rouven

first: Jaber-Hijazi

last: Farah


title: Clonal CD8 T cells orchestrate arrhythmogenic inflammation in immune checkpoint inhibitor-associated myocarditis

city: Houston

first: Sung Wook

last: Kang

state: TX

address: one plaza

department: Surgery

institute: Baylor college of medicine

summary: Objective: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but are frequently associated with immune-related adverse events, particularly in combination regimens. ICI-associated myocarditis (ICI-M) is rare but highly lethal, with a mortality rate approaching 50% and a notable risk of fatal ventricular arrhythmias. Prevention and effective management of ICI-M remain significant clinical challenges. This study aims to elucidate the immune landscape and spatial organization of immune cells in ICI-M using single-cell multi-omics in a preclinical mouse model. Methods: We utilized Ctla4+/–Pdcd1–/– mice, modeling human ICI-induced myocarditis. Single-cell RNA (scRNAseq) and T cell receptor (TCR) sequencing were performed on heart-infiltrating immune cells and peripheral blood mononuclear cells (PBMCs). Spatial transcriptomics was applied to map immune infiltration in cardiac tissue. Results: Approximately half of Ctla4+/–Pdcd1–/– mice died after 100 days, while Ctla4+/+ mice showed normal survival. ECG monitoring identified ventricular arrhythmias in 15% of Ctla4+/–Pdcd1–/– mice. Histology revealed severe myocardial inflammation and fibrosis. Cardiac scRNAseq data indicated that T cells were the predominant immune population in ICI-M hearts. TCR sequencing demonstrated substantial overlap in TCR clonotypes between cardiac-infiltrating and circulating CD8+ T cells. These TCR-shared CD8+ T cells exhibited an activated phenotype and were enriched in pathways associated with allograft rejection and inflammation. Spatial mapping revealed localization near the AV node and subendocardium, implicating potential CD8+ T cell–mediated conduction disruption. Conclusion: Clonal, activated CD8+ T cells contribute to arrhythmogenic myocarditis in ICI-M. Targeting specific TCR-peptide-MHC interactions may enable myocarditis prevention without impairing antitumor efficacy.

first: Hyun-sung

last: Lee


title: Single cell RNA Sequencing of murine tdTomato positive skin cells with or without HIRA knockout [dataset 1]

first: Peter

last: Adams


title: Decoding cellular stress states for toxicology using single-cell transcriptomics

status: Public on Jun 10 2025

city: Research Triangle Park

first: Imran

last: Shah

state: NC

address: Mail Code: D143-02

department: Office of Research and Development

institute: US Environmental Protection Agency

summary: Single-cell transcriptomics (SCTr) offers a powerful platform for decoding the complexities of cellular stress responses to chemical exposures, capturing rare and transient subpopulations that can be obscured in bulk measurements. This study employs SCTr to profile the responses of HepaRG liver cells to various stress-inducing chemicals, providing detailed insights into adaptive stress response pathways (SRPs), encompassing the response to unfolded proteins, oxidative stress, heat shock, and DNA damage. By leveraging SCTr, we identify distinct cellular subpopulations and elucidate their transcriptomic profiles, linking specific gene expression patterns to biological mechanisms underlying stress responses. Our findings demonstrate the utility of SCTr in discerning the dose-dependent effects of chemicals at a granular level, highlighted by key differences between pseudo-bulk and single-cell analysis. Chemicals such as troglitazone, brefeldin A, rotenone, and tunicamycin induced unique transcriptional signatures associated with specific stress response pathways. Single-cell connectivity mapping with signatures of SRPs and cell fates, including autophagy and apoptosis, revealed clusters of cells with adaptive and potentially adverse phenotypes. These SCTr data have implications for identifying toxicological and disease mechanisms involving adaptive stress pathways. The data can also provide unique insights into toxicological processes by beginning to resolve adaptive chemical exposures, where cells recover, from those that are adverse from which cells do not recover, offering potentially new approaches for chemical safety assessments.

overall_design: We profiled reference perturbagens known to induce stress responses, including the unfolded protein response (UPR), oxidative stress response (OSR), heat-shock response (HSR), response to hypoxia (HPX), and DNA damage response (DDR), in the differentiated HepaRG human liver cell model at three different concentrations. HepaRG cells were dissociated and fixed for single-cell transcriptomic (SCTr) assessments. Here, cells were profiled with Biospyder TempO-LINC v1.0.

first: David

last: Gallegos

first: Brian

last: Robinette

first: Bryant

last: Chambers

first: Dennis

last: Eastburn

first: Douglas

last: Bell

first: Salvatore

last: Camiolo

first: Kevin

last: White

first: Nicole

last: Martin

first: Gioele

last: Montis

first: Joel

last: McComb

first: Bruce

last: Seligmann

last: Chorley


title: Defective plasticity in dermatomyositis patients muscle stem cells is associated with sustained intrinsic inﬂammatory signaling and disruption of the histone H3.3 chromatin loading pathway [CUT&RUN]

status: Public on Jun 08 2025

city: Leuven

first: Wilhelm

last: Bouchereau

email: wilhelm.bouchereau@kuleuven.be, patrick.lomonte@univ-lyon1.fr, benedicte.chazaud@inserm.fr, armelle.corpet@univ-lyon1.fr

state: Vlaams brabant

address: ON4 - Herestraat 49 PB 804

department: Stamcelinstituut Leuven

country: Belgium

institute: KU-Leuven

summary: Skeletal muscle regeneration is driven by muscle stem cells (MuSC). They proliferate then differentiate to restore muscle function. This process, known as myogenesis, is driven both by intrinsic properties of MuSCs and by extrinsic inflammatory signals. While proinflammatory signals are necessary for healthy muscle regeneration, chronic inflammation participates in different pathologies affecting the skeletal muscle, including cancer-associated cachexia, Duchenne muscular dystrophy (DMD) or auto-immune disorders. Dermatomyositis (DM) is characterized by infiltration of immune cells in the peri-fascicular area which is associated with chronic inflammation. Although anti-inflammatory treatments are commonly used to combat the disease, most patients never fully regain their muscle strength. MuSCs derived from dermatomyositis patients exhibit impaired myogenesis in vitro, indicating that these cells may have acquired intrinsic defects that contribute to the disease. We compared the transcriptomes of MuSCs from healthy individuals and DM patients, finding that the latter are unable to effectively execute the myogenic transcriptomic program during ex vivo differentiation. Additionally, they exhibit an intrinsically activated canonical TNF signaling. MuSC from DM patients also exhibit reduced expression of H3.3 and its chaperone genes, coupled with a decrease in H3.3 deposition across the entire genome. The global loss of H3.3 combined with elevated intrinsic TNF signaling is associated with a failure of DM-derived MuSCs to suppress inflammatory signals and achieve proper myogenesis, suggesting a mechanistic link between epigenetic dysregulation and defective muscle regeneration.

overall_design: CUT&RUN against H3.3 profiling of human skeletal muscle stem cells derived from either healthy control or dermatomyositis patients grown in vitro in either proliferating condition and after day 3 of switch to differentiating condition.

first: Linda

last: Chenane

first: Lola

last: Lessard

first: Michèle

last: Weiss-Gayet

first: Yseult

last: Cardona

first: Rémi

last: Mounier

first: Laure

last: Gallay

first: Yves

last: Allenbach

first: Olivier

last: Benvéniste

first: Armelle

last: Corpet

first: Bénédicte

last: Chazaud

first: Patrick

last: Lomonte


title: Defective plasticity in dermatomyositis patients muscle stem cells is associated with sustained intrinsic inﬂammatory signaling and disruption of the histone H3.3 chromatin loading pathway [RNA-seq]

overall_design: RNA-seq profiling of human skeletal muscle stem cells derived from either healthy control or dermatomyositis patients grown in vitro in either proliferating condition and after day 1 and day 3 of switch to differentiating condition.


title: Gastruloids enable modeling of the earliest stages of human cardiac and hepatic vascularization

status: Public on Jun 04 2025

city: Stanford

first: Oscar

last: Abilez

address: Clark Center E276, 318 W Campus Dr

department: Cardiothoracic Surgery

institute: Stanford University

summary: Here we show that spatially micropatterned human pluripotent stem cell (hPSC)-derived gastruloids enable in vitro modeling of the earliest developmental stages of cardiac vascularization, roughly corresponding to the first three weeks of in vivo human development (Carnegie Stages 9 and 10). Using clues from developmental biology, we identified a growth factor/small molecule cocktail, that when added to micropatterned hPSCs, generated a spatially organized, branched, and lumenized vascular network within a multi-lineage cVO comprising endocardial, myocardial, epicardial, and neuronal cell types.

overall_design:
Our single cell RNA-seq (scRNA-seq) data includes one (1) Control (standard cardiac differentiation) and four (4) groups of cVOs (standard cardiac differentiation + vascular factors).

Our bulk RNA-seq (bRNA-seq) includes data for cardiac and hepatic systems. In the cardiac system, there are three groups and a total of 39 samples: 1. hESC-3R at D0 only (3 replicates/timepoint x 1 timepoint = 3 total samples); 2. Control at Days 2, 5, 8, 10, 12, and 16 of differentiation (3 replicates/timepoint x 6 timepoints = 18 total samples); 3. cVO at Days 2, 5, 8, 10, 12, and 16 of differentiation (3 replicates/timepoint x 6 timepoints = 18 total samples). In the hepatic system, there are four groups and a total of 12 samples: 1. hESC-3R at D0 only (3 replicates/timepoint x 1 timepoint = 3 total samples) *Note: this group/replicates were used both for cardiac and hepatic systems; 2. Control at Day 20 of differentiation (3 replicates/timepoint x 1 timepoint = 3 total samples); 3. hVO-D3 at Day 20 of differentiation (3 replicates/timepoint x 1 timepoint = 3 total samples); 4. hVO-D6 at Day 20 of differentiation (3 replicates/timepoint x 1 timepoint = 3 total samples).

Our single cell RNA-seq (scRNA-seq) data includes one (1) Control (standard cardiac differentiation) and four (4) groups of cVOs (standard cardiac differentiation + vascular factors).

first: Joseph

last: Wu

first: Ioannis

last: Karakikes


title: Interleukin-6 Trans Signaling and STAT-3 Activation Promote Neutrophilic Inflammation in Alcohol-Associated Hepatitis

status: Public on Jun 01 2025

city: Davis

first: Gaurav

last: Sarode

address: 6404A GBSF, 451 E. Health Sciences Dr.

department: Internal Medicine

institute: University of California, Davis

summary: Alcohol associated hepatitis (AH) is characterized by neutrophilic inflammation leading to liver injury. Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates hepatic regeneration and hepatic acute phase responses. In the liver IL-6 can signal through either membrane-bound or soluble IL-6 receptors (IL-6R).Aims:to determine the role of IL-6 trans signaling in the pathogenesis of alcohol-associated hepatitis.Methods:Using human liver RNA-Seq, we compared expression of IL-6 signaling pathway components in 51 patients with no liver disease (N=10), early alcohol-related steatohepatitis (early ASH, N=12), non-severe AH (N=11) and severe AH (N=18). Ingenuity Pathway Analysis was used to determine upstream regulators of IL-6 receptor expression. For in vitro studies, HepG2 cells were cultured overnight with either TGF-β1 (5 ng/ml) or 1% FBS, and STAT3 was activated with either 1) IL-6 to simulate classical signaling or 2) hyper-IL-6, a recombinant IL-6/IL-6Rα peptide that selectively activates trans-IL-6 signaling. RNA-Seq was performed on stimulated cells to define an IL-6 trans-signaling gene signature. This signature was used to define a patient subset with high IL-6TS activity (IL-6TS high). For in vivo studies, female mice 14-16 years old were treated with a 10 day chronic-plus binge ethanol liver injury model.Results:Human liver RNA-Seq data demonstrated declining IL-6R expression with progressively increasing severity, and pathway analysis of 3,513 differentially expressed genes identified TGF-β1 as the strongest negative upstream regulator of IL-6R expression in AH. Despite reduced IL-6R expression, STAT3-dependent gene expression was enhanced in severe AH. In vitro, TGF-β1 suppressed STAT3 phosphorylation by both classical and trans IL-6 signaling. However, only high-dose hyper-IL-6 (20 ng/ml) restored STAT3 activation, while TGF-β1-mediated suppression of STAT3 persisted despite high-dose IL-6 (20 ng/ml) treatment. RNA-Seq of hyper-IL-6-stimulated hepatocytes was enriched in genes associated with neutrophil recruitment, and we identified a set of 11 co-clustered genes that characterized a subset of AH patients with enhanced expression of these IL-6TS-inducible transcripts (IL-6TS high). These patients exhibited increased intrahepatic neutrophilic infiltration on liver biopsies and enrichment of pathways associated with leukocyte migration on IPA analysis. In mice, ethanol treatment increased hepatic STAT3 activation despite reduced IL-6R and gp130 expression, and ethanol enhanced expression of neutrophil chemoattractants, includingIcam1,Lbp, andLcn2.Conclusion:Together, these findings suggest that trans IL-6 signaling preserves hepatocyte STAT3-dependent expression of neutrophil chemoattractants in AH. Future studies will examine if inhibiting IL-6 trans signaling abrogates neutrophilic inflammation in AH.

overall_design:
Using human liver RNA-Seq, we compared expression of IL-6 signaling pathway components in 51 patients no liver disease early alcohol-related steatohepatitis (early ASH, N=12), non-severe AH (N=11) and severe AH (N=18). Ingenuity Pathway Analysis was used to determine upstream regulators of IL-6 receptor expression.
For in vitro studies, HepG2 cells were cultured overnight with either TGF-β1 (5 ng/ml) or 1% FBS, and STAT3 was activated with either 1) IL-6 to simulate classical signaling or 2) hyper-IL-6, a recombinant IL-6/IL-6Ra peptide that selectively activates trans-IL-6 signaling. RNA-Seq was performed on stimulated cells to define an IL-6 trans-signaling gene signature.  This signature was then used to define a subset of patients with high IL-6TS activity (IL-6TS high).
For in vivo studies, female mice 14-16 years old were treated with a 10 day chronic-plus binge ethanol model of alcohol-related liver injury, and liver tissues was assessed with Western Blot and qPCR.

first: Vikrant

last: Rachakonda