title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [MV4-11 5hmC-seq]

summary: Enhancing ten-eleven translocation 2 (TET2) activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TET2 in malignant cells due to pharmacokinetic constraints and the need for chromatin remodeling to enable effective cellular reprogramming. Here, we identify a novel mechanism to enhance TET2 activity via all-trans retinoic acid (ATRA), which induces retinoic acid receptor alpha (RARA)-mediated TET2 transcription in myeloid leukemia cells and synergizes with ascorbate to promote DNA hydroxymethylation and chromatin remodeling at key myeloid differentiation loci. Using Tet1/2/3-deficient mice and primary human acute myeloid leukemia (AML) models, we show that ATRA plus ascorbate more effectively induces differentiation, inhibits leukemia stem cell self-renewal in a TET2-dependent manner, and sensitizes AML cells to targeted therapies in vivo, leading to improved survival. These findings support the combined use of ATRA and ascorbate as a strategy to enhance TET2 activity for the treatment of myeloid malignancies.

overall_design: Reduced representative (MspI-digested) enzymatic 5hmC base-resolution sequencing of MV4-11 cells treated 72hr with 250μM LAA, 1μM ATRA, the combination thereof, or vehicle controls (PBS/DMSO).

middle: E

first: Yoon Sing

middle: I


title: Characterization of m6A modified RNAs in ox-LDL treated coronary artery smooth muscle cells

status: Public on Oct 01 2025

city: Nanjing

first: Yahong

last: Fu

state: Jiangsu

address: Guangzhou Road

country: China

institute: the First Affiliated Hospital of Nanjing Medical University

summary: To comprehensively analyze the characteristics of m6A modified RNAs in HCASMCs with ox-LDL treated and control group and search for new diagnostic markers and therapeutic targets for CAD. We then performed m6A modified RNAs expression profiling analysis using data obtained from meRIP-seq of cells treated with 50ug/ml ox-LDL or control.

overall_design: Human coronary artery smooth muscle cells (HCASMCs) were treated with ox-LDL at 50 mg/L for 24 h to model the abnormal lipid metabolism in vitro of CAD. Then, differential expression profiles of m6A modified RNAs were generated by deep sequencing, in triplicate, using Illumina.

first: Shu

last: He

first: Xiongkang

last: Gan

first: Yanjun

last: Wang

first: YaQing

last: Zhou

first: Rongli

last: Jiang

first: Qian

last: Zhang

first: Yang

last: Pan

first: Chengcheng

last: Li

first: Hanxiao

first: Xiumei

last: Chen

first: Enzhi

last: Jia


title: RNA sequencing identified differentially expressed genes in the mesocorticolimbic and nigrostriatal systems of compulsive METH taking rats.

status: Public on Sep 30 2025

city: Baltimore

first: Atul

last: Daiwile

state: MD

address: 251 Bayview Blvd,

department: MNRB

country: USA

institute: NIDA

type: Expression profiling by high throughput sequencing

summary: Methamphetamine (METH) is an extremely addictive drug which continues to cause significant harm to individuals and communities. Differences in patterns of abuse, amounts of METH taken, and in relapse rates exist among METH users who meet DSM-V criteria for METH use disorder (MUD). We are actively investigating the behavioral and molecular differences between compulsive and non-compulsive METH self-administering (SA) rats in the presence of a foot-shock which serves as an aversive stimulus. In the present study, we used male rats that were trained to self-administer METH (0.1 mg/kg/infusion, IV) on an FR-1 schedule for 20 days using a pattern of three 3-h sessions per day and followed by foot-shocks (0.18mA to 0.36mA) for the next 9 days. All the METH taking rats escalated their drug intake during the 20 days of training phase. During the foot-shock phase, a group of rats continued to self-administer METH in the presence of aversive stimuli and were called shock-resistant (SR, compulsive), whereas others who decreased their intake were termed shock-sensitive (SS, non-compulsive). Animals were euthanized 2 hours after the last SA session and the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (DStr) and midbrain (MBr) were isolated for RNA sequencing. RNA sequencing showed a large number of differentially expressed genes (DEGs) in all the brain regions. Our study supports the notion that studying multiple brain regions is critical for a comprehensive understanding of the interconnected neuroadaptive changes which are associated with substance use disorders (SUDs). The present study is of significant translational importance by further supporting the idea that targeting common DEGs identified across multiple brain regions might lead to the development of effective therapeutic approaches against MUD.

overall_design: We trained rats to self-administer METH for 20 days. Then, under the same conditions, the rats continued to self-administer METH in the presence of a foot shock for 9 days.

first: Nasser

last: Adjei

first: Bruce

last: Ladenheim

first: Michael

middle: T

last: McCoy

first: Vikrant

last: Palande

first: JeanLud

last: Cadet

middle: P


title: PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN 2]

city: Research Triangle Park

first: Francesco

middle: John

last: DeMayo

state: North Carolina

address: 111 T W Alexander Dr

department: DIR

institute: NIEHS

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Progesterone, acting through its isoform receptors PGR-A and PGR-B, is essential for regulating uterus function. The ratio between these isoforms is dynamic and context-dependent, driving distinct transcriptional programs. The upstream mechanisms controlling the PGR isoform balance and their functional impact in the uterus remain poorly understood. In this study, we identified two distal PGR enhancers in endometrial stromal cells located 60 kb and 220 kb upstream of the PGR transcription start site. We found that in comparison to PGR promoter-targeting which favors a PGR-B dominant profile, activation of these enhancers shifts the isoform ratio by increasing PGR-A and decreasing PGR-B expression. Bulk RNA-sequencing revealed that the isoform balance alters the progesterone-regulated transcriptome. PGR-A/B-equivalent cells displayed pro-inflammatory gene signatures, whereas PGR-B-dominant cells exhibited suppression of inflammatory signaling and cell cycle activity. Cut&Run assays identified differential genomic binding patterns associated with each isoform profile, and integration with chromatin interaction maps suggest direct regulation of distinct gene subsets. Upstream, ESR1 indirectly activated the PGR-A isoform dominantly, potentially through cooperation with FOXO1 at the U2 enhancer. This study identifies a novel enhancer-driven mechanism regulating PGR isoform dynamics and sheds light on how their imbalance in the endometrial stroma may reshape progesterone signaling in health and disease.

overall_design: PGR Cut&Run in two THESC cell-lines with activated PGR isoforms at different ratios, treated with vehicle or 1uM Medroxyprogesterone Acetate (MPA) for 3 hours.

first: Skylar

middle: G

last: Montague Redecke

first: Austin

last: Bell-Hensley

first: MyeongJin

last: Yi

first: Shuyun

middle: J


title: TMEM16F Phospholipid Scramblase Regulates Tumorigenesis by Modulating the Tumor Immune Microenvironment

city: ShenZhen

first: Menghan

last: Wu

address: Guangqiao Road

department: Institute of Molecular Physiology

institute: ShenZhen Bay laboratory

summary: The immunosuppressive tumor microenvironment enables immune evasion through mechanisms beyond canonical immune checkpoints. While phosphatidylserine (PS) externalization coordinates apoptotic clearance under physiological conditions, tumors exploit this pathway by mimicking apoptotic cells through PS exposure to suppress immune responses.  Genetic ablation of TMEM16F abolished PS exposure, systemically reprogrammed the tumor microenvironment and primary immune organs toward immune activation, and suppressed tumor growth across cancer models.

overall_design: We performed single-cell RNA-seq (scRNA-seq) of tumor-infiltrating lymphocytes (TILs) from the TME of vector control or TMEM16F KO MC38 cells engrafted mice at 21 days. Total 10,782 single cells from MC38 colorectal tumor, colored by 14 cell types. The data demonstrated that the frequency of CD8+ T cell, NK cell, macrophage, myeloid-derived suppressor cell (MDSC), and Treg cell subsets were affected by TMEM16F deletion. Further analysis using flow cytometry and immunofluorescent staining confirmed the scRNA-seq findings, which indicated higher ratios of CD8+ T cells, NK cells, and M1 macrophages in the TMEs of TMEM16F KO mice.

first: M

first: S

last: Shi

first: Y


title: Single Cell RNA-seq of PgrCre/+Srfflox/flox  and Srfflox/flox mouse uterus at gestation day 3.5

summary: Single cell RNA-seq analysis demonstrated dramatic changes in adult PgrCre/+Srfflox/flox endometrial cell populations compared to Srf flox/flox controls. Uterine Srf ablation caused myeloid immune cell infiltration, and differential expression analysis demonstrated that PgrCre/+Srfflox/flox stromal fibroblasts downregulated  progesterone-regulated genes and growth response genes. Proliferating fibroblast populations shifted from G2-M phase-dominant in controls to S-G2 phase-dominant in PgrCre/+Srfflox/flox uteri. PgrCre/+Srfflox/flox epithelial cells overexpressed estrogenic and innate inflammatory genes.

overall_design: Uterine tissues from two mice staged at gestation day 3.5 (3 days after finding vaginal plug) were pooled for each sample, and 2  samples per genotype (from 4 mice per genotype) were sequenced.

first: Ryan

middle: M

last: Marquardt

first: Sara

middle: A

last: Grimm

first: San-Pin

first: John

last: Lydon


title: PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells [CUT&RUN]

overall_design: Immortalized human endometrial stroma cells (THESC) were engineered with the CRISPR activation system to activate the Estrogen Receptor Alpha gene. ESR1 activated THESC were then treated with 10 nM E2 for 24 hours and Cut&Run was conducted with a FOXO1 Antibody.

last: Li


title: Cortical versus hippocampal network dysfunction in a human brain assembloid model of epilepsy and intellectual disability

city: Los Angeles

first: Ranmal

middle: Aloka

last: Samarasinghe

state: California

address: 710 Westwood Plaza

department: Neurology

institute: University of California, Los Angeles

summary: Neurodevelopmental disorders often impair multiple cognitive domains. For instance, a genetic epilepsy syndrome might cause seizures due to cortical hyperexcitability and present with memory impairments arising from hippocampal dysfunction. This study examines how a single disorder differentially affects distinct brain regions by using human patient iPSC-derived cortical- and hippocampal-ganglionic eminence assembloids to model Developmental and Epileptic Encephalopathy 13 (DEE-13), a condition arising from gain-of-function mutations in the SCN8A gene. While cortical assembloids showed network hyperexcitability akin to epileptogenic tissue, hippocampal assembloids did not, and instead displayed network dysregulation patterns similar to in vivo hippocampal recordings from epilepsy patients. Predictive computational modeling, immunohistochemistry, and single-nucleus RNA sequencing revealed changes in excitatory and inhibitory neuron organization that were specific to hippocampal assembloids. These findings highlight the unique impacts of a single pathogenic variant across brain regions and establish hippocampal assembloids as a platform for studying neurodevelopmental disorders.

overall_design: We generated iPSC-derived organoids from a DEE-13 patient, with a gain-of-function variant (p.R1872>L) in the SCN8A gene, associated with refractory seizures and intellectual disability. Organoids from this patient line (Mut) as well as matched CRISPR-corrected control line (iCtrl) were directed toward cortical, hippocampal, or ganglionic eminence (GE) fates. On Day 59, GE organoids were fused with cortical (Cx) or hippocampal (Hc) organoids.

first: Colin

last: McCrimmon


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis

city: Oxford

first: Alison

last: Simmons

address: John Radcliffe Hospital/Headley Way

department: The MRC Weatherall Institute of Molecular Medicine

country: United Kingdom

institute: University of Oxford

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

overall_design: Refer to individual Series


title: Maternal mRNA Clearance Prevents Precocious Transcription and Genome Instability in Mouse Early Embryos [ATAC-seq]

city: Hangzhou

first: Heng-yu

last: Fan

state: Zhejiang

address: Yuhangtang Road

institute: Life Sciences  Institute

summary: Oocytes accumulate abundant maternal mRNAs during the growth stage of meiotic maturation after transcriptional silencing, and early embryo development prior to zygotic genome activation (ZGA). During the oocyte-to-zygote transition, the selective and stepwise clearance of maternal transcripts is a prerequisite for the initiation of zygotic development. Maternal mutations in genes involved in mRNA clearance, including Pabpn1l, Cnot6l, and Btg4, lead to early embryonic arrest at the one-to-two cell stage in both mice and humans; however, the direct underlying mechanism is unclear. In the present study, optimized low-input sequencing methods of newly transcribed RNAs (neo-RNAs) were used, and the results provide evidence that the arrested zygotes abnormally accumulate transcription-associated DNA damages and R-loops in pronuclei. Ectopic R-loop formation and DNA strand breaks are accompanied by increased chromatin accessibility and leakage of maternal genes that should be turned off following fertilization. Abnormal R-loop accumulation causes the retardation of DNA replication and S-phase arrest during the first mitotic cell cycle. Overexpression of RNase H1 in maternal Pabpn1l knockout zygotes can remove genomic R-loops and partially reverse developmental defects. Collectively, the conjoint analysis of chromatin accessibility and neo-RNA transcription indicated that the failure of maternal mRNA clearance in mouse zygotes results in leakage transcription and extra R-loop formation, which is the primary reason for DNA replication stress, genome instability, and zygotic cell cycle arrest.

overall_design: Each sample contained 50 zygotes collected from mated female mice 28 h after the hCG injection. After removing zona pellucida with acidic M2 (pH 2.5), zygotes were washed with DNase/RNase-free 0.2% BSA and collected in DNA-lowering binding tubes. The lysis buffer was added directly after sample collection. Tn5 enzyme in Chromatin Profile Kit for Illumina (Novoprotein; N248) was used to fragment chromatin at 37 ℃ on Thermo Mixer (TS100) with 1000 rpm for 30 min and stopped using stop buffer. After extraction with DNA extract beads, DNA fragments were amplified for 15 cycles using the following PCR conditions: 72 ℃ for 3 min; 98 ℃ for 30 s; and thermocycling at 98 ℃ for 15 s, 60 ℃ for 15 s and 72 ℃ for 8 s; following by 72 ℃ 2 min. After the PCR, libraries were purified with 1.2 × DNA clean beads, followed by fragment selection with 0.5×/0.7× beads.

first: Heng-Yu

first: Qian-Qian

last: Sha

first: Yun-Wen

first: Meng-Yan

last: Jia

first: Yu

last: Jiang

first: Xing-Xing

last: Dai

first: Long-Wen

last: Zhao


title: Maternal mRNA Clearance Prevents Precocious Transcription and Genome Instability in Mouse Early Embryos [S4U-seq]

overall_design: Each sample contains 50 zygotes collected from mated female mice at 26 h after hCG injection were cultured in KSOM containing 200 μM 4-Thiouridine (S4U) (Sigma; T4509) for 2 h for labeling. After washing with DNase/RNase-free 0.2% BSA, samples were collected in DNase/RNase-free tubes. Total RNA was extracted using TRIzol reagent, and ribosomal RNA was removed using the rRNA depletion module (Abclonal; RK20348). The alkylation was performed using iodoacetamide (Sigma; I1149). Total RNA after iodoacetamide treatment was used as the input for library construction using the Fast RNA-seq Lib Prep Kit V2 (Abclonal; RK20306). DNA fragments were selected, and the final sequencing libraries were constructed from to 300-400 bp of the amplified cDNA. Sequencing data were extracted on the Illumina HiSeq X Ten platform in the 150 bp paired-end mode.


title: Exogenous Estrogen Enhances T Cell Activation in Male Primates

city: Lund

first: Joan

last: Escrivà-Font

state: Skåne

address: Sölvegatan 19

department: Department of Laboratory Medicine, Faculty of Medicine

country: Sweden

institute: Lund University

summary: Estrogen influences T cell development and enhances infection resistance in females, but its immunological effects during gender-affirming hormone therapy (GAHT) remain poorly understood. Here we characterize immune adaptations in male rhesus macaques (RMs) treated with 17β-estradiol (E2) or placebo over 7 months. E2 therapy suppressed endogenous testosterone production, induced female physical traits, and altered blood cell counts and chemistry profiles. Additionally, E2 treatment attenuated innate immune responses while increasing T cell activation. Following mRNA vaccination, E2-treated RMs exhibited significantly higher frequencies of CCR5+ CD4+ T cells, the primary targets for HIV-1 replication, compared to placebo-treated RMs. Overall, our findings reveal the immunological consequences of estrogen in male primates, emphasizing the need to investigate how supraphysiological E2 levels may affect HIV susceptibility and pathogenesis. This work highlights the potential of RMs as a model for studying immune interventions in the context of GAHT.

overall_design: RNA-seq of whole blood EDTA from 17β-estradiol- and placebo-treated rhesus macaques at study weeks 0, 7, 13, 18, 19, 23, and 27.

first: Patricia

last: Hahn

first: Eric

middle: S

last: Alexander

first: Kimberly

last: Weisgrau

first: Tianling

last: Ou

first: Wenhui

last: He

first: Daniel

last: O'Hagan

first: Laura

middle: C

last: Da Silva

first: Noah

last: Gurley

first: Li

last: Lin

first: Michael

middle: D

last: Cameron

first: Eva

last: Rakasz

last: Farzan

first: Saverio

last: Capuano III

first: Camila

middle: R

last: Consiglio

first: Mauricio

last: Martins


title: Serum response factor is essential for endometrial function and prevention of inflammatory fibrosis

first: Francesco

last: DeMayo

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Macrophage programming rewires cancer‑cell phenotypes

city: Schlieren

first: Florence

last: Vallelian

address: Wagistrasse 12

department: Department of Internal Medicine

country: Switzerland

institute: University Hospital and University of Zurich

summary: To determine how macrophage states dictate cancer cell phenotype dynamics, we conducted a time-resolved, multiplexed scRNA-seq experiment of mixed cell spheroids composed of M-CSF macrophages and MC38 cancer cells. We collected the spheroids on days 1 and 5 after formation and processed approximately 9000 per condition. After demultiplexing and quality control, 178939 cells were retained and visualised by UMAP, recalculated separately for macrophages and tumor cells. We found that the macrophages occupy distinct transcriptional spaces on day 1, which reflect their prior cytokine imprinting. By day 5, macrophages converge onto a single “tumor-educated” cluster, indicating that paracrine cues from tumor cells override their original states and impose a common transcriptional programme. Macrophage centroid dispersion decreased, confirming transcriptional convergence. In contrast, transcriptional divergence of tumor cells increased between day 1 and 5. To define the macrophage state-dependent effects on tumor cells, we pre‑defined three transcriptomic modules—proliferation, epithelial‑to‑mesenchymal transition (EMT), and stress/hypoxia—based on our previous single‑cell atlas of MC38 spheroids (Schaer et al. 2023; Schaer et al. 2025). We then calculated a score for each module per tumor cell. On day 1, nearly all tumour cells scored as proliferative (high G2M_checkpoin score) regardless of macrophage polarization. By day 5, the score distributions diverged. Spheroids containing unpolarized and IFN‑γ macrophages remained proliferative, those with IL‑4‑ or TGF‑β macrophages lost their proliferation signature and shifted markedly toward EMT, while tumor cells in the absence of macrophages acquired a strong hypoxia signature. Spheroids with IL-10 polarized macrophages induced an intermediate pattern. Hence, anti‑inflammatory macrophages preferentially steer MC38 cells toward an EMT‑like, low‑proliferation, pro‑invasive state, whereas pro‑inflammatory IFN‑γ macrophages keep tumor cells locked in a proliferative programme. Simultaneously, the tumor microenvironment erases macrophage-of‑origin signatures, illustrating rapid, bidirectional cross-talk and plasticity within the 3D niche.

overall_design: 9000 spheroids per condition containing MC38 alone (tumour‑only) or MC38 plus M‑CSF macrophages (untreated) or MC38 plus M-CSF macrophages treated with either IFN-γ, IL-4, IL-10 or TGF-β were harvested on days 1 and 5 for pooled scRNA‑seq

first: Dominik

last: Schaer

first: Livio

last: Baselgia

first: Elena

last: Duerst

first: Matthias

last: Peterhans


title: Comparative Single Cell Transcriptome Analysis of c-Met Receptor Expressing and Non-Expressing Projection Neurons in the Developing Frontal and Visual Cortices

first: Kathie

last: Eagleson

state: CA

address: 4650 Sunset Blvd.

institute: Children's Hospital Los Angeles

summary: Single cell transcriptomic analyses in adult mice show that cortical projection neuron (PN) subclasses exhibit heterogenous gene expression profiles that reflect their projection targets, and laminar and areal positions. Further analyses revealed that PNs within the same subclass also exhibit transcriptomic heterogeneity. The MET receptor tyrosine kinase, a regulator of synapse maturation, is expressed in a subpopulation of select cortical PN subclasses, providing an experimental model to address transcriptomic heterogeneity within PN subclasses. Single cell RNA sequencing and smFISH identified transcriptomic differences between Met+ and Met- PN populations in the mouse visual and frontal cortices during the early phase of synapse formation and dendritic growth. Analyses confirmed enrichment of Met in select PN subclasses and further identified astrocytes as the major source of its ligand, Hgf. No genes were expressed uniquely in Met+ or Met- PNs within a subclass; rather, there were graded differences in gene expression between the populations. While the identity of differentially expressed genes varied between subclass and cortical area, there was a consistent overrepresentation of genes associated with axon growth, and synapse structure, development and function, with a subset associated with the MET interactome. Further, expression differences in genes associated with maturation indicate less mature excitatory synapses and spines in the Met+ population at this age. These findings suggest that Met+ neurons do not represent a functional subtype within a PN subclass. Rather, the data are consistent with converging lines of biochemical and electrophysiological evidence that MET contributes to asynchronous maturation of developing cortical circuits.

overall_design: P7-P9 frontal and visual cortices were microdissected and analyzed using 10X scRNA sequencing

first: Ramin

last: Ali Marandi Ghoddousi

first: Zia

last: Rady

first: Pat

last: Levitt


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis - scRNA-Seq

first: Alison

last: Simmons

summary: Crohn's disease often presents with fistulae, abnormal tunnels connecting the intestine to the skin or other organs. Despite the profoundly adverse impact of fistulae on patient morbidity, the molecular basis of their formation remains unclear, largely due to the challenge of capturing intact fistula tracts and their inherent heterogeneity. Here, we construct an unbiased, subcellular-resolution spatial expression atlas of 62 intestinal fistulae spanning diverse anatomical locations. We describe fistula-associated epithelial, immune and stromal cell states, revealing abnormal zonation of growth factors and morphogens linked to establishment of tunnelling anatomy. We identified fistula-associated stromal (FAS) fibroblasts assembled in concentric layers, forming a proliferative, lumen-adjacent zone (LAZ) underlying surface neutrophil and macrophage-rich granulation tissue, followed by active lesion core FAS cells all encircled by quiescent, pro-fibrotic outer zone (FOZ) fibroblasts. We mapped fistula tract ECM architecture and demonstrated FAS populations locate to different collagen structures, exhibiting functional properties spanning proliferation, migration and active ECM remodelling, to dense collagen deposition and fibrosis. We define niches supporting epithelialization of fistula tunnels and a putative precursor FAS population detected at the base of ulcers in non-penetrating Crohn’s. This precursor population co-localises with inflammatory as opposed to pro-fibrotic SPP1+ macrophages and fails to induce developmental transcription factors, observed in FAS populations located in fistula tracts.  Our study demonstrates that common molecular pathways and cellular niches underpin fistulae arising at different intestinal locations and reveal the cellular protagonists of fistula establishment and persistence. Our resource will inform development of model systems and interventions that mitigate aberrant fibroblast activity while preserving their regenerative properties in Crohn’s.

overall_design: Cells from small intestinal tissue samples in patients with Crohn's disease and healthy controls were profiled using single cell RNA-Seq. Cell pools were either enriched for epithelium (EPCAM+), immune (CD45+) or stromal cells (CD45- EPCAM-). Samples were subjected to 5' scRNA sequencing with feature barcoding, yielding Gene expression, CITE-seq and TCR information.

first: Colleen

last: McGregor

first: Tarun

last: Gupta

first: Zinan

last: Yin

first: Esther

last: Bridges

first: Verena

last: Lentsch

first: David

last: Fawkner-Corbett

first: Chloe

middle: H

last: Lee

first: Ruchi

last: Tandon

first: Katherine

last: Baker

first: Anna

last: Aulicino

first: Jan

last: Bornschein

first: Paulina

last: Siejka-Zielinska

first: Zoe

last: Christoforidou

first: Marta

last: Jagielowicz

first: Kexin

last: Xu

first: Sorayya

last: Moradi

first: Maria

last: Greco

first: Cyril

last: Lai

first: Jana

last: Koth

first: Mark

last: Bignell

first: Bruce

last: George

first: Eve

last: Fryer

last: Vieth

first: Agne

last: Antanaviciute


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [U-937 5hmC-seq]

city: Miami

first: Luisa

last: Cimmino

state: Florida

address: 1501 NW 10th Ave, BRB 711

institute: University of Miami

type: Methylation profiling by high throughput sequencing

overall_design: Enzymatic reduced representation base-resolution 5hmC-seq of U937 cells treated 72hr with 1uM ATRA, 250uM LAA, ATRA+LAA, or vehicle control to determine differential hydroxymethylation status

first: Tiffany

last: Leesang

first: John

last: Brabson

first: Yoon Sing

last: Yap

first: Aristeidis

last: Telonis


title: An RNA sponge directs the transition from feast to famine in Caulobacter crescentus

city: Würzburg

first: Manuel

last: Velasco Gomariz

address: Josef-Schneider-Straße 2/D15

country: Germany

institute: Helmholtz Institute for RNA-based Infection Research (HIRI)

summary:
In bacteria, regulatory networks controlling the adaptation of gene expression in response to stress are frequently complemented by base-pairing small regulatory RNAs (sRNAs) that act at the post-transcriptional level. While many regulatory circuits governing stress resilience have been studied in the model bacterium Caulobacter crescentus, only a small fraction of its diverse sRNA repertoire has been characterized.
In this study, we globally identify interacting RNA-RNA pairs associated with the major RNA-binding protein Hfq in C. crescentus. In addition to numerous connections between sRNAs and mRNAs, we also recover RNA-RNA pairs consisting of two non-coding transcripts. Our results indicate that the sRNA CrfA acts as a sponge to inactivate a family of four conserved sRNAs, SisA-D. When induced by carbon starvation, CrfA redirects gene expression towards the utilization of distinct energy sources, and loss of the RNA sponge is linked to a severe growth defect in environments with fluctuating nutrient availability.

overall_design: Transcriptomic of Caulobacter NA100 ΔvanAB pBVMCS6-EV (KFS-96), Caulobacter NA100 ΔvanAB pBVMCS6-SisA (KFS-1401), Caulobacter NA100 ΔvanAB pBVMCS6-CrfA (KFS-1375), Caulobacter NA100 ΔvanAB ΔsisA-D pBVMCS6-EV (KFS-1746), Caulobacter NA100 ΔvanAB ΔsisA-D pBVMCS6-SisA (KFS-1944) &  Caulobacter NA100 ΔvanAB ΔsisA-D pBVMCS-CrfA (KFS-2097),  after 15´ of addition on 500 µM Vanillate to induce the sRNA. Cells were growing in M2G medium at 30°C until they reached OD660=0.3. 500 µM Vanillate was added to the cells and after 15´ samples were collected for RNAprep.

first: Kathrin

last: Fröhlich

first: Laura

middle: N

last: Vogt


title: Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma [ChIP-seq]

city: Camperdown

first: George

middle: Louis

last: Joun

state: NSW

address: John Hopkins Drive

department: School of Medical Sciences

country: Australia

institute: The University of Sydney

summary: Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screens, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings reveal a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.

overall_design: PRDM9 Knock-out RKI1 glioblastoma stem cell line was treated with +/- 10µM CMPD1 for 72 hours. The KO cell line was compared to Non-Targetted Control (NTC) RKI1 glioblastoma stem cell line, also treated with +/- 10µM CMPD1 for 72 hours, of the same transduction batch and passage number within each biological replicate. There are two biological repeats. We excluded RKI1 n=2 NTC UT (Sample013) from downstream analysis due to suspected sample degradation in the H3K4me3 ChIP sample.

first: Lenka

last: Munoz


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [U-937 ATAC-Seq]

summary: Enhancing TET2 activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TET2 in malignant cells due to pharmacokinetic constraints and the need for chromatin remodeling to enable effective epigenetic reprogramming. Here, we identify a novel mechanism to enhance TET2 activity via all-trans retinoic acid (ATRA), which induces RARA-mediated TET2 transcription in myeloid leukemia cells and synergizes with ascorbate to promote DNA hydroxymethylation and chromatin remodeling at key myeloid differentiation loci. Using Tet1/2/3-deficient mice and primary human AML models, we show that ATRA plus ascorbate more effectively induces differentiation, inhibits leukemia stem cell self-renewal in a TET2-dependent manner, and sensitizes AML cells to targeted therapies in vivo leading to improved survival. These findings support the combined use of ATRA and ascorbate as a strategy to enhance TET2 activity for the treatment of myeloid malignancies.

overall_design: To understand the effect of ATRA + LAA on altering chromatin accessibility, U-937 cells were treated 72hr with 1uM ATRA, 250uM L-ascorbic acid (LAA), the combination thereof, or vehicle controls, then ATAC-seq was performed.

middle: E

first: Felipe

last: Beckedorff


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [U-937 RNA-Seq]

overall_design: RNA-seq of U-937 cells treated 72hr with 1uM ATRA, 250uM LAA, ATRA+LAA, or vehicle control to determine differential gene expression


title: Cytokine–ontogeny interaction shapes macrophage transcriptional states (GM-CSF–derived macrophages)

first: Florence

last: Vallelian

summary: In GM-CSF–derived macrophages, bulk RNA-seq was performed on five biological replicates per cytokine condition (IL‑4, IFN‑γ, IL‑10, TGF‑β). IL‑4 separated along PC1 (47% variance) but showed no additional Hallmark enrichment.  PC2 (25% variance) distinguished the IFN‑γ pole characterized by IRF1/STAT1-regulated genes (Gbp genes, Cxcl9), from IL‑4 and IL‑10/TGF‑β poles, denoting distinct remodeling programs. These data establish an ontogeny‑dependent divergence at the transcriptomic level.

overall_design: GM-CSF–derived macrophages were stimulated with IL‑4, IFN‑γ, IL‑10, TGF‑β, or left untreated (control). Bulk RNA-seq was performed on five biological replicates per condition.

first: Dominik

last: Schaer

first: Livio

last: Baselgia

first: Elena

last: Duerst

first: Matthias

last: Peterhans


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation [MV4-11 ATAC-seq]

summary: Enhancing ten-eleven translocation 2 (TET2) activity through genetic or pharmacologic approaches, such as ascorbate supplementation, can slow myeloid malignancy progression. However, ascorbate alone may be insufficient to fully activate TET2 in malignant cells due to pharmacokinetic constraints and the need for chromatin remodeling to enable effective cellular reprogramming. Here, we identify a novel mechanism to enhance TET2 activity via all-trans retinoic acid (ATRA), which induces retinoic acid receptor alpha (RARA)-mediated TET2 transcription in myeloid leukemia cells and synergizes with ascorbate to promote DNA hydroxymethylation and chromatin remodeling at key myeloid differentiation loci. Using Tet1/2/3-deficient mice and primary human acute myeloid leukemia (AML) models, we show that ATRA plus ascorbate more effectively induces differentiation, inhibits leukemia stem cell self-renewal in a TET2-dependent manner, and sensitizes AML cells to targeted therapies in vivo, leading to improved survival. These findings support the combined use of ATRA and ascorbate as a strategy to enhance TET2 activity for the treatment of myeloid malignancies.

overall_design: MV4-11 AML cells were treated 72hr with LAA (250µM) + ATRA (1µM) and then assayed for changes in chromatin accessibility by ATAC-seq


title: PGR Isoform Modulation via Enhancer Activation Regulates Progesterone Signaling in Human Endometrial Stromal Cells

first: Francesco

last: DeMayo


summary: Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy-induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings demonstrate a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells.

overall_design: Drug Treated glioblastoma stem cell line RKI1, followed by ChIP-seq. Treatment with tubulin inhibitor CMPD1 (10uM) +/- PRDM9 inhibitor MRK-740 (3uM) for 72 hours.


title: Methylation reprogramming associated with aggressive prostate cancer and ancestral disparities

status: Public on Sep 29 2025

first: Jenna

last: Craddock

address: Johns Hopkins Dr

institute: University of Sydney

type: Methylation profiling by genome tiling array

summary: African men are disproportionately impacted by aggressive prostate cancer (PCa). Key to this disparity both genetic and environmental factors, alluding to epigenetic modifications. However, African-inclusive prostate tumour DNA methylation studies are lacking.Assembling a multi-geo-ancestral prostate tissue cohort, including men with (57 African, 48 European, 23 Asian) or without (65 African) PCa, we interrogate for genome-wide differential methylation. Overall, methylation appears to be driven by ancestry over geography (152 southern Africa, 41 Australia). African tumours show substantial heterogeneity, with universal hypermethylation indicating more pervasive epigenetic silencing, encompassingPCa suppressor genes and enhancer-targeted binding motifs. Conversely, African tumour-associated heterochromatic hypomethylation suggests chromatin relaxation anddevelopmental pathway activation via enhancer targets. Notably, non-prostate lineage elements appeared preferentially exploited in African tumorigenesis, with ancestry potentiallyinfluencing the extent of lineage-inappropriate activation, and tumour progression marked by repression of developmental regulators. Together, these findings point to extensive epigenetic plasticity in African tumours, with intergenic regulatory remodelling promoting genomic instability, metastatic potential and aggressive disease phenotypes.

overall_design: This study included a total of 286 prostate tissue samples from men with or without prostate cancer, of which 193 samples were selected for downstream analysis. Samples were derived from snap-frozen prostate cores collected across two geographic regions: southern Africa and Australia. Each sample was assigned to one of three genetically confirmed ancestry groups: African (n = 122), European (n = 48) or Asian (n = 23). Samples included both tumour (n = 128) and non-tumour (n = 65) tissues. Genome-wide DNA methylation profiling was conducted using the Illumina Infinium MethylationEPIC BeadChip platform (v1.0 and v2.0). Epigenome-wide association studies were performed to identify ancestry-associated (African vs. non-African) and tumour-associated (African tumour vs. non-tumour) differential methylation.

first: M.S. Riana

last: Bornman

first: Vanessa

last: Hayes


title: Arid2 promotes Follicular B-cell differentiation and antibody responses in vivo

status: Public on Sep 26 2025

city: St. Louis

middle: P.

last: Souroullas

state: MO

address: 660 S. Euclid Av

department: Medicine

institute: Washington University School of Medicine

summary: SWI/SNF chromatin remodeling complexes, also known as BAF complexes, regulate gene expression during development and differentiation.  These complexes exist in distinct variants, including the polybromo-associated BAF (PBAF) complex, defined by the ARID2 core subunit. ARID2 is frequently mutated in B cell leukemias, but its role in normal B cell development remains unknown. Using conditional knockout mice, we show that Arid2 deletion impairs B cell differentiation in vivo. Mb1-Cre–mediated deletion, active in early progenitors, caused a marked reduction of splenic and circulating Follicular B cells, whereas CD19-Cre deletion produced a milder phenotype. These defects were not due to altered proliferation or survival but reflected impaired differentiation potential.  Transcriptomic profiling of isolated pro-B, pre-B, and Follicular B cells revealed that Arid2 loss disrupts stage-specific gene expression programs, with cumulative downregulation of B cell receptor signaling and altered lineage-specifying pathways.  Functionally, Arid2-deficient mice exhibited impaired germinal center expansion after immunization and reduced IgG antibody production. Together, these findings identify Arid2 as a critical regulator of B cell differentiation and maturation by coordinating transcriptional programs during early lymphopoiesis.

overall_design: RNA sequencing performed on B cell progenitors harvested from the bone marrow and follicular B cells harvested from the spleen of the indicated genoetypes.  Cells were isolated by FACS and processed from RNA sequencing.

first: Rachel

middle: L

last: Paolini


title: Dual-patterned pluripotent stem cells self-organize into a human embryo model with extended anterior-posterior patterning

status: Public on Sep 25 2025

city: Seattle

first: Chengxiang

last: Qiu

state: WA

address: William H. Foege Hall, 3720 15th Ave NE

department: Genome Sciences

institute: University of Washington

summary: Human gastruloids are a powerful class of stem cell-derived models that recapitulate key features of early embryonic development, including symmetry breaking and the emergence of three germ layers. However, they lack anterior embryonic structures and coordinated axial organization. To address this limitation, we pre-patterned human pluripotent stem cells (hPSCs) by exposing them to either anterior (FGF2) or posterior (CHIR99021 [CHIR] & retinoic acid [RA]) cues. Upon mixing, these dual-patterned hPSCs interacted and self-organized into elongated structures with both anterior and posterior features—which we term anterior-posterior (AP) human gastruloids. Anteriorly pre-treated cells robustly intercalated into posteriorly pre-treated cells, collectively giving rise to a continuum of neural tissues—including a brain-like domain, a neural tube-like structure, and neuro-mesodermal progenitors (NMPs)—with segmented somites arrayed bilaterally. Single cell RNA sequencing (scRNA-seq) revealed that human AP gastruloids contain cell types resembling the midbrain-hindbrain boundary (MHB), regionalized hindbrain structures (i.e. rhombomeres 1–8), regionalized neural crest (i.e. cranial, vagal, trunk) and head mesoderm. Transcriptomic comparisons to primate embryos revealed that human AP gastruloids most closely resemble Carnegie stage 11 (CS11) embryos. While they lack a notochord and full dorsal-ventral polarity, human AP gastruloids recapitulate key spatial and temporal features of early neurulation and somitogenesis. Perturbation of folic acid metabolism or rho-associated kinase (ROCK) signaling induced spinal cord defects, phenocopying aspects of spina bifida and other neural tube defects, highlighting this model’s potential for studying congenital disorders. AP gastruloids may serve as a simple, robust, scalable platform for modeling coordinated human AP body axis development. More broadly, our results suggest that controlled interactions between differentially prepatterned progenitors can initiate self-organization of complex body axis features. The “pattern-and-mix” strategy may serve as a generalizable framework for assembling spatially organized stem cell models of mammalian development.

overall_design: In this study, we generated anterior-posterior (AP) human gastruloids from pre-patterned human pluripotent stem cells (hPSCs). Briefly, hPSCs were treated with either anterior cues (FGF2) or posterior cues (CHIR99021 and retinoic acid). After pre-patterning, the two populations were mixed, enabling them to interact and self-organize into elongated structures with coordinated anterior-posterior features. At 120 hours, AP gastruloids were collected and pooled for single-cell profiling using 10X Genomics technology.

first: Zukai

last: Liu

first: Connor

last: Kubo

first: Stella

last: Xu

first: Riza

last: Daza

first: Eva

last: Nichols

first: Wei

last: Yang

first: Anh

last: Vo

first: Mary

last: O’Neill

first: Charlie

last: Lee

first: Jay

last: Shendure

first: Nobuhiko

last: Hamazaki


title: Mot1 regulation of promoter binding by TBP varies with gene expression levels and stress independently of coactivator-dependence [RNA-Seq]

city: Bethesda

first: Alan

last: Hinnebusch

state: Maryland

address: 49 Convent Drive Bldg49/Rm 6A30

institute: NIH, NICHD

summary: Mot1 is an essential Snf2-family ATPase in budding yeast that regulates transcription by dissociating the general initiation factor TBP (TATA-binding protein) from DNA. Previous studies showed that in optimum growth conditions Mot1 preferentially removes TBP from stress-responsive promoters that utilize the coactivator SAGA to enhance TBP binding at TFIID-dependent promoters of “housekeeping” genes. In stress conditions of amino acid starvation, by contrast, we found that Mot1 promotes high-level TBP occupancy at genes activated by transcription factor Gcn4, enriched for SAGA-dependent promoters, and at highly-transcribed subsets of constitutively expressed SAGA- and TFIID-dependent genes, while suppressing TBP occupancies at lowly transcribed genes regardless of SAGA/TFIID dependence. Importantly, the response to Mot1 depletion for genes induced by starvation or oxidative stress switched from decreased to increased TBP occupancies when transcribed at low basal levels in non-stressed cells. Notably, reduced TBP binding on Mot1 depletion impairs transcription of highly expressed TFIID genes but not highly expressed SAGA/stress-activated genes, implying that promoter activation by SAGA produces a surfeit of incomplete preinitiation complexes dependent on Mot1 for their formation.

overall_design: Total RNA isolation was carried out using Hot-Phenol Method.Followed by RNA-sequencing libraries preparation using the Illumina TrueSeq stranded mRNA Library Prep Kit. Ribo-depletion was performed to remove the rRNA using Qiagen FastSelect Yeast rRNA Depletion Kit, followed by paired-end sequencing using the Novaseq-X platform.

first: Priyanka

last: Mittal


title: Mot1 regulation of promoter binding by TBP varies with gene expression levels and stress independently of coactivator-dependence [ChIP-Seq]

overall_design: Immunopurification of formaledhyde-fixed and sonicated DNA fragments that were subjected to paired-end sequencing


title: AMPK signaling downstream of adenosine 2A receptor represses Th17 cell pathogenicity through epigenetic and metabolic reprogramming.

status: Public on Sep 27 2025

city: Athens

first: Dimitris

last: Valakos

address: Soranou Ephessiou 4

department: Center of Basic Research

country: Greece

institute: Biomedical Reasearch Foundation Academy of Athens

summary: Metabolic reprogramming controls protective or pathogenic Th17 cell responses; still, the precise molecular pathways that drive distinct immunometabolic states remain elusive. Here, we demonstrate that non-pathogenic Th17 cells induced by the immunoregulatory cytokine activin- A display reduced aerobic glycolysis and increased oxidative phosphorylation (OXPHOS). Notably, signaling through the adenosine A 2A receptor (A 2A R)/AMP-activated protein kinase (AMPK) axis in response to activin-A, boosts OXPHOS and reprograms pathogenic Th17 cells towards non-pathogenic states. Epigenetic studies revealed that pathogenic Th17 cells express highly the CBP/P300 binding protein (PCAF) which facilitates the acetylation of histone 3 at lysine 9 (H3K9ac) at genes related to the mammalian target of rapamycin complex 1 (mTORC1), glycolysis and Th17 pathogenicity programs. Instead, activin-A-treated Th17 cells display an AMPK-mediated suppression of PCAF activity and aerobic metabolism while, accumulate H3K9ac in gene loci related to OXPHOS. Collectively, we uncover A 2A R-AMPK as a central metabolic checkpoint that epigenetically regulates Th17 pathogenicity.

overall_design: We performed H3K9ac and PCAF ChIP-seq in pathogenic and non-pathogenic Th17 cells induced in the absence or presence of Activin-A, respectively.

first: Gina

last: Papadopoulou

first: Dimitrios

first: Georgina

last: Xanthou


title: Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation

first: Luisa

last: Cimmino

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

overall_design: Refer to individual Series

first: Tiffany

last: Leesang

first: John

middle: P

last: Brabson

first: Yoon Sing

last: Yap

first: Felipe

last: Beckedorff

first: Aristeidis

last: Telonis


title: Molecular Signatures in Acutely Suicidal Patients Without Somatic Comorbidities

status: Public on Sep 24 2025

city: Ulm

first: Karlheinz

last: Holzmann

address: Helmholtzstreet 8/1

department: Medical Faculty

institute: Ulm University

summary:
Major Depressive Disorder (MDD) is a debilitating mental health condition affecting millions worldwide.
One critical yet often underexplored variable in MDD is the biological sex. Women are diagnosed with depression twice as often as men, account for two-thirds of suicide attempts, and tend to experience greater symptom severity, earlier onset, and longer depressive episodes.

overall_design: We analyzed blood plasma-based genome-wide gene expression using Affymetrix microarrays in 14 acutely suicidal patients (seven males, seven females) with no comorbid somatic or psychiatric disease, compared to a healthy, age- and gender-matched control group.

first: Michael

last: Fritz

first: Judith

last: Streb

first: Manuela

last: Dudeck


title: Spatially Resolved Insights Into Fistulating Crohn’s Disease Pathogenesis - Visium Spatial Transcriptomics

first: Alison

last: Simmons

overall_design: This study employed Visium FFPE spatial transcriptomics to investigate the molecular landscape of Crohn's disease across different phenotypic manifestations, including fistulizing, stricturing, and inflammatory subtypes, in comparison to healthy controls. A total of 36 slides were analyzed, comprising tissue sections from patients diagnosed with Crohn's disease and non-diseased controls. The spatially resolved transcriptomic profiling was performed on formalin-fixed, paraffin-embedded (FFPE) tissue samples, enabling high-resolution analysis of gene expression within the spatial context of the tissue architecture. Some slides contain more than one tissue section (see meta data).

first: Colleen

last: McGregor

first: Tarun

last: Gupta

first: Zinan

last: Yin

first: Esther

last: Bridges

first: Verena

last: Lentsch

first: David

last: Fawkner-Corbett

first: Chloe

last: Lee

first: Ruchi

last: Tandon

first: Katherine

last: Baker

first: Anna

last: Aulicino

first: Jan

last: Bornschein

first: Paulina

last: Siejka-Zielinska

first: Zoe

last: Christoforidou

first: Marta

last: Jagielowicz

first: Kexin

last: Xu

first: Sorayya

last: Moradi

first: Maria

last: Greco

first: Cyril

last: Lai

first: Jana

last: Koth

first: Mark

last: Bignell

first: Bruce

last: George

first: Eve

last: Fryer

last: Vieth

first: Agne

last: Antanaviciute


title: Gene expression profile of miR-517a-3p overexpressing choriocarcinoma cells.

status: Public on Sep 21 2025

city: Nagoya

first: Kosuke

last: Yoshida

state: Aichi

address: 65 Tsuruma-cho

country: Japan

institute: Nagoya University

summary: MicroRNAs play fundamental roles in the development of various cancers; however, the molecular mechanisms underlying choriocarcinoma remain unclear. In this study, we investigated the gene expression profiles of miR-517a-3p overexpressing choriocarcinoma cells.

overall_design: To investigate the function of miR-517a-3p, we overexpressed it in BeWo and JEG3 cells and performed RNA sequencing.

first: Yuki

last: Nishiko

first: Akira

last: Yokoi

first: Kaoru

last: Niimi


title: In-Depth Analysis of Obesity-Associated Changes in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells and Primary Cilia Function

status: Public on Sep 20 2025

city: Frankfurt

first: Nina-Naomi

last: Kreis

address: Theodor-Stern-Kai 7

department: Department of Gynecology and Obstetrics

institute: University Hospital Frankfurt, J. W. Goethe- University

summary: Adipose tissue-derived mesenchymal stromal/stem cells (ASCs) possess regenerative potential. Obesity induces a pro-inflammatory environment that compromises their function. We investigated how obesity affects ASC biology, focusing on primary cilia. Our data reveal that obesity alters ASC gene expression, particularly in pathways related to the extracellular matrix, transforming growth factor-β (TGFβ) signaling, cell motility, and differentiation. The gene levels of regulatory factor X2 (RFX2) and adenylate cyclase 3 (ADCY3), important for ciliary biogenesis, were downregulated in obese ASCs. TGFβ treatment significantly decreases the expression of RFX2 and ADCY3 in lean ASCs. Knockdown of ADCY3 reduced primary cilium length, whereas pharmacological activation restored it and improved cell motility. These results suggest that obesity impairs ASC ciliary function, contributing to defective adipogenesis and reduced regenerative capacity. Restoring ADCY3 activity partially rescues ciliary integrity and cellular function, highlighting the role of primary cilia in ASC dysfunction and offering potential therapeutic targets for obesity-related disorders.

overall_design: Adipose tissue-derived mesenchymal stromal/stem cells (ASC) were isolated from subcutaneous (sub) adipose tissue samples from women undergoing cesarean section. Total RNA was extracted from five individual ASC samples per group: lean (body mass index, BMI < 25, SUB25), obese 35 (BMI ≥ 35, SUB35), and obese 40 (BMI ≥ 40, SUB40), and subjected to whole-genome RNA sequencing (RNA-seq).

first: Alexandra

last: Friemel

first: Andreas

last: Ritter

first: Anna Elisabeth

last: Hentrich

first: Esther

last: Siebelitz

first: Frank

last: Louwen

first: Juping

last: Yuan


title: An ORAI1 mutation with mixed loss and gain of function properties causes combined immunodeficiency

status: Public on Sep 23 2025

city: New York

first: Maxwell

last: McDermott

state: NY

address: 550 1st Ave

department: Pathology

institute: NYU Langone Health

summary: Loss of function mutations of ORAI1 suppress store-operated Ca2+ entry (SOCE) and cause an immunodeficiency disorder called Ca2+ release-activated Ca2+ (CRAC) channelopathy. An infant patient who is compound heterozygous for His134Pro and Leu194Pro mutations in the ORAI1 gene had strongly reduced SOCE in response to T cell receptor stimulation. He suffered from a severe form of combined immunodeficiency (CID) resulting in fatal chronic cytomegalovirus infection. Single cell transcriptomics revealed an overall strong activation of the patient's T cells but attenuated CD8+ effector memory T cell function.

overall_design: PBMCs of ORAI1 lose of function mutation patient(ORAI1 p.H134P/p.L194P), and his heterozygous mother(ORAI1 p.L194P/WT) were acquired and analyzed via single cell RNA-seq

first: McDermott

last: Maxwell

first: Noyer

last: Lucile

first: Feske

last: Stefan


title: Toxoplasma gondii chromatin remodeler SWI/SNF controls parasite division and stage specific gene expression

status: Public on Sep 17 2025

city: Nanning

first: Dandan

last: Hu

state: China

address: Daxue East Rd #100, College of Animal Science and Techenology, Guangxi University.

institute: Guangxi University

summary: The SWI/SNF complex is evolutionarily conserved across species, initially identified in yeast, and later associated with various human cancers. In research on Toxoplasma gondii, this complex specifically creates nucleosome-free regions (NFRs) at the promoters of male gamete-specific genes, thereby activating their expression. Disruption of this complex results in the loss of male gametes. Although the SWI/SNF complex is relatively conserved across species, its specific role in T. gondii remains unclear. In this study, we first catalogued the core ATPase subunits of chromatin remodeling complexes and characterized the function of the SWI/SNF ATPase subunits TgSNF2a and TgSNF2b. We found that deletion of these two subunits severely impaired tachyzoite growth and altered the mode of division from endodyogeny to endopolygeny. Disruption of the complex led to a reduction in chromatin accessibility, suppressed stage-specific gene expression during the tachyzoite stage, and indirectly upregulated early endodyogeny stage (EES) genes by downregulating transcriptional repressors such as AP2XII-2 and AP2XII-5, and disrupting interactions with the MORC complex. Consequently, the knockout strains exhibited a shift in gene transcription toward the EES stage. These results provide new insights into the epigenetic regulation of sexual reproduction in T. gondii, offering potential strategies for controlling toxoplasmosis.

overall_design:
To assess the functions of TgSNF2a and TgSNF2b in T. gondii, an indole-3-acetic acid (IAA) degradation (mAID) system was used to generate inducible knockdown (iKD) of TgSNF2a and TgSNF2b parasites. Double knockdown parasites were also pruduced by using mAID system. Potentially regulated genes of TgSNF2a and TgSNF2b were investigated by RNA-seq using iKD parasites with or without IAA treatment for 24 or 72 hours.  Two or three biological replicates were employed.
To further characterize the genome occupancy of TgSNF2a and TgSNF2b, CUT&Tag experiments were performed using the endogenously 3xHA tagged parasite and ME49 strain.

first: Xuan

last: Li

first: Jiayi

last: Huang

first: Xueqin

last: Zou

first: Hongbin

last: Si

first: Xun

last: Suo

first: Xingju

last: Song


title: Arabidopsis TRB Proteins Form Two Closely Related Complexes to Mediate H3K4me3 Demethylation and Transcriptional Repression

city: Beijing

first: xinjian

last: He

address: No. 7, zhongguancun life science park road, changping district

institute: National Institute of Biological Sciences

first: Xin


title: Reproducibility of PD patient-specific midbrain organoid data for in vitro disease modelling (timepoints)

status: Public on Sep 18 2025

city: Belval

first: Matthieu

last: Gobin

address: 6, avenue du Swing

country: Luxembourg

institute: LCSB

summary: Midbrain organoids are advanced in vitro cellular models for disease modelling. They have been used successfully over the past decade for Parkinson’s disease (PD) research and drug development. The three-dimensional structure and multicellular composition allow disease research under more physiological conditions than is possible with conventional 2D cellular models. However, there are concerns in the field regarding the organoid batch-to-batch variability and thus the reproducibility of the results. In this manuscript, we generate multiple independent midbrain organoid batches derived from healthy individuals or GBA-N370S mutation-carrying PD patients to evaluate the reproducibility of the GBA-N370S mutation-associated PD transcriptomic and metabolic signature as well as selected protein abundance. Our analysis shows that GBA-PD-associated phenotypes are reproducible across organoid generation batches and time points. This proves that midbrain organoids are not only suitable for PD in vitro modelling, but also represent robust and highly reproducible cellular models.

overall_design: RNA sequencing data of midbrain organoids from 3 healthy (WT1-3) and PD patients with GBA-N409S mutation (GBA1-3). Data comes from 30 or 60 days old organoids (D30 or D60) and 4 individual organoid generation batches (B1-4).

first: Elisa

last: Zuccoli

first: Haya

last: Al Sawaf

first: Mona

last: Tuzza

first: Sarah

last: Nickels

first: Alise

last: Zagare

first: Jens

last: Schwamborn


title: Small RNA sequencing for choriocarcinoma and complete hydatidiform mole samples

first: Kosuke

last: Yoshida

type: Non-coding RNA profiling by high throughput sequencing

summary: MicroRNAs play fundamental roles in the development of various cancers. In this study, we investigated the miRNA profiles of choriocarcinoma (CC) and complete hydatidiform mole (CHM) samples.

overall_design: To investigate the miRNA profiles of trophoblastic diseases, we extracted RNA from 11 FFPE samples of choriocarcinoma from nine patients using laser capture microdissection. Moreover, 5 FFPE samples of CHM were used as control. Then, small RNA sequencing was performed.

first: Yuki

last: Nishiko

first: Akira

last: Yokoi

first: Kaoru

last: Niimi


title: Germinal center-mediated broadening of B cell responses to SARS-CoV-2 booster immunization

status: Public on Sep 16 2025

first: Julian

last: Zhou

address: 425 S. Euclid Ave.

department: Pathology & Immunology

institute: Washington University in St. Louis

summary: Germinal centers (GC) are key sites for antibody diversification and affinity maturation. SARS-CoV-2 mRNA vaccines elicit robust GC B cell responses in humans, but how these influence the breadth of immunity against viral variants remains unclear. We analyzed GC B cell responses in nine healthy adults following mRNA booster immunization. We show that 77.8% of the B cell clones in the GC expressed representative monoclonal antibodies (mAbs) recognizing the spike protein, with 37.8% of these targeting the receptor-binding domain (RBD). One RBD-targeting mAb, mAb-52, neutralized all tested SARS-CoV-2 strains, including the recent XEC variant. mAb-52 utilized the IGHV3-66 public clonotype, protected hamsters challenged against the EG.5.1 variant, and targeted the class I/II RBD epitope, closely mimicking the binding footprint of ACE2. Its broad reactivity was driven by extensive somatic hypermutation, underscoring the critical role of GC reactions in shaping cross-variant B cell immunity following SARS-CoV-2 booster vaccination.

overall_design: Ultrasound-guided fine needle aspirates (FNA) samples from five participants with detectable S+ GC B cells were selected for scRNA-seq. The samples were collected on d57 post-boost from the axillary lymph nodes.

first: Sameer

middle: K

last: Malladi

first: Deepika

last: Jaiswal

first: Baoling

last: Ying

first: Wafaa

middle: B

last: Alsoussi

first: Tamarand

last: Darling

first: Bernadeta

last: Dadonaite

first: Alesandro

last: Civljak

first: Stephen

last: Horvath

middle: Q

first: Wooseob

last: Kim

first: Jackson

last: Turner

first: Aaron

last: Schmitz

first: Fangjie

last: Han

first: Suzanne

last: Scheaffer

first: Christopher

middle: W

last: Farnsworth

first: Raffael

last: Nachbagauer

first: Baliana

last: Nestorova

first: Spyros

last: Chalkias

first: Michael

last: Klebert

first: Darin

last: Edwards

first: Robert

last: Paris

first: Benjamin

last: Strnad

first: William

last: Middleton

first: Jane

last: O'Halloran

first: Rachel

last: Presti

first: Jesse

last: Bloom

first: Adrianus

last: Boon

last: Diamond

first: Goran

last: Bajic

first: Ali

last: Ellebedy


title: The Mechanism of PEDV-Induced Exosomes from Intestinal Epithelial Cells Inhibiting Macrophage Migration and Phagocytic Function-scRNA seq

status: Public on Sep 03 2025

city: nanjing

first: qiu

last: zhong

address: No. 1 Weigang, Xuanwu District

department: College of Veterinary Medicine

institute: Nanjing Agricultural University

summary: Virus-induced inflammation has long served as a canonical hallmark of host immune activation. Paradoxically, the same pathogen can sculpt an immunosuppressive milieu that accelerates its own dissemination.

overall_design: Here we show that, although porcine epidemic diarrhea virus (PEDV) rapidly triggers intestinal epithelial cells to secrete pro-inflammatory cytokines and chemokines—thereby amplifying epithelial–macrophage crosstalk and engaging RIG-I and Toll-like receptor signaling in macrophages—the cells’ phagocytic, endocytic, and lysosomal effector pathways are markedly repressed. Mechanistic dissection revealed that PEDV-infected epithelial cells release exosomes that potently inhibit macrophage migration and phagocytosis. Exosomal miR-190a, induced by PEDV, targets tropomodulin-3 (TMOD3), disrupting actin capping, reducing cellular stiffness and adhesion, and consequently impairing macrophage motility. Concomitantly, PEDV-induced exosomal lncRNA TS-2083 binds ANXA2, facilitating its ubiquitin-dependent degradation and disrupting phagocytic-cup formation, thereby attenuating macrophage engulfment. Notably, after oral PEDV challenge, piglet serum contains circulating exosomes enriched in miR-190a and lncRNA TS-2083 that recapitulate the same inhibitory effects on macrophage migration and phagocytosis. Our findings reposition PEDV immune evasion from “interferon antagonism” to “cross-cell communication reprogramming,” providing a new theoretical framework and translational roadmap for dissecting pathogenesis and designing host-directed interventions against porcine coronaviruses and other mucosa-tropic viruses.

first: Qiu

last: Zhong


title: A time-gated PKA–CREB signaling circuit licenses IL-12 responsiveness and Th1 fate in CD4⁺ T cells

status: Public on Sep 15 2025

city: NEW YORK

first: Jingyao

last: Zhao

address: 701 W 168th Street Room 1204

department: Microbiology and Immunology

institute: Columbia University Medical Center

summary: Naïve CD4⁺ T cells differentiate into Th1 cells upon TCR stimulation in the presence of IFN-γ and IL-12. However, the intracellular signaling networks that temporally coordinate these inputs to reinforce Th1 lineage commitment remain incompletely defined. Here, we identify protein kinase A (PKA) as a time-gated regulator of IL-12 responsiveness and Th1 differentiation. Using a conditional knockout mouse model that deletes both catalytic PKA subunits in CD4⁺ T cells, we show that PKA is dispensable for early T cell activation but is essential for the late-phase induction of IL-12 receptor β2 (Il12rb2) and STAT4. PKA-deficient CD4⁺ T cells fail to differentiate into Th1 cells in vitro and cannot induce Th1-mediated colitis in vivo. Instead, they adopt a Th2-skewed phenotype and drive eosinophilic lung inflammation and fibrosis. Mechanistically, prolonged TCR stimulation induces the expression of the peptide hormone Adrenomedullin (Adm) and its receptor component Ramp3, which activate PKA and its downstream effector CREB. Activated CREB drives Il12rb2 and Stat4 transcription, establishing a feedforward circuit that integrates signal duration with cytokine responsiveness. In the absence of PKA, this transcriptional program fails to initiate, leading to impaired IL-12 signaling and a loss of Th1 identity. These findings define a PKA–CREB signaling module that links sustained antigen stimulation to transcriptional and epigenetic commitment in CD4⁺ T cells, offering a mechanistic explanation for the temporal gating of Th1 differentiation and the prevention of Th2-driven tissue pathology.

overall_design: Control or PKAKO naïve CD4 T cells were enriched by CD4 isolation Kit and sorted by FACS. Activated T cells were generated by stimulation by antiCD3/CD28 for 3 days. For forskolin treatment, cells were rested with IL7 for 3 day and then treated by 1ug/mL for 4 hours.

first: Sankar

last: Ghosh


title: Single cell map of the adult female mouse urethra reveals epithelial and stromal macrophages with distinct functional identities

status: Public on Sep 10 2025

city: Bengaluru

first: Diya

last: Binoy Joseph

state: Karnataka

address: GKVK - Post, Bellary Rd

country: India

institute: Institute for Stem Cell Science and Regenerative Medicine

summary: We have employed single cell RNA-sequencing to create a cellular atlas of the female mouse urethra. The epithelial lining of the urethra is an understudied mucosal barrier. Emerging evidence points to the role of the urethra in pathogen surveillance, sensation and response.  To investigate the heterogeneity of the resident immune niche in the adult female mouse urethra, we performed single cell RNA-sequencing which revealed the presence of distinct epithelial-associated and stromal macrophages in the urethra.

overall_design: Wildtype CD-1 adult female mouse urethras were digested to single cells for sc-RNA seq using the 10x Genomics platform. To assess immune cell distribution in the epithelial and stromal compartments, adult female mouse urethras were enzymatically digested and the epithelial and stromal compartments were separated  mechanically. Resultant tissue was digested into single cells and subjected to single cell RNA-sequencing to obtain cell types enriched in the epithelial and stromal compartments of the urethra.


title: Single cell RNA sequencing of the adult female mouse urethra with transurethral instillation of Lipopolysaccharide (LPS) compared to PBS instilled mice

summary: We have employed single cell RNA-sequencing to create a cellular atlas of the female mouse urethra. The epithelial lining of the urethra is an understudied mucosal barrier. Emerging evidence points to the role of the urethra in pathogen surveillance, sensation and response. In this study, we instilled female mice transurethrally with PBS or LPS (1 mg/ml) and collected urethras at 3 hours post-instillation. Single cell RNA-sequencing was performing to assess changes in immune and epithelial cell types after LPS treatment.

overall_design: Wildtype CD-1 adult female mice were transurethrally instilled with PBS (100 microliter) or bacterial lipopolysaccharide (LPS, 1 mg/ml, 100 microliter). Urethras were dissected 3 hours post-instillation and digested to obtained single cells. Three mice each were pooled for the PBS and LPS group. Single cell RNA-sequencing was performed using 10x Genomics 3' gene expression kit.


title: Spatial immune profiling defines a subset of human gliomas with functional tertiary lymphoid structures [Xenium]

status: Public on Sep 01 2025

city: Frankfurt am Main

first: Katharina

last: Imkeller

address: Heinrich-Hoffmann-Str. 7

institute: University Hospital Frankfurt

summary: Adult-type diffuse gliomas, the most common primary brain tumors, respond poorly to immune-based therapies and are considered immunologically "cold" tumors. Here, we examined the features and clinical relevance of glioma intratumoral tertiary lymphoid structures (TLSs) using spatial transcriptome and proteome profiling. In a cohort of 642 gliomas, TLSs were present in 15% of tumors and associated with a remodeled perivascular space and spatial redistribution of extracellular matrix components. Three distinct TLS subtypes could be defined based on differing cellular composition and immune activity. While all subtypes lacked classical germinal center architecture, certain TLSs exhibited features of dynamic immune functions, including clonal T and B cell expansion, generation of IgA⁺ and IgG⁺ plasma cells, and dendritic cell-T cell interactions. The presence of TLSs with active immune response features correlated with improved overall survival. Thus, a functional adaptive immune response is detectable in some gliomas, with implications for stratification and treatment.

overall_design: To explore the molecular and cellular architecture and immunological function of glioma-associated TLS, we analyzed 642 glioma specimens from the Frankfurt University Cancer Center. We found that 15% of gliomas had B cell aggregates (TLS+), while the rest did not (TLS-).We used a multi-modal spatial profiling approach, including spatial transcriptome profiling, whole slide multiplex immunofluorescence staining, and high-plex immunofluorescence staining, on consecutive tissue sections to trace single TLS through different molecular layers.We performed bulk RNA sequencing on 64 gliomas, with and without TLS, matched for IDH status, age, and gender. We examined the transcriptional profiles of 61 TLS from 20 tumors using spatial transcriptome profiling. We then analyzed 12 TLS+ patients using spatial single-cell profiling using a custom 468-gene panel (Xenium, 10x Genomics).

first: Pinar

last: Cakmak

first: Jennifer

last: Lun

first: Aakanksha

last: Singh

first: Jadranka

last: Macas

first: Jonathan

last: Schupp

first: Jonas

last: Schuck

first: Zeina

last: Mahmoud

first: Miriam

last: Köhler

first: Tatjana

last: Starzetz

last: Burger

first: Eike

last: Steidl

first: Lucie

middle: M

last: Hasse

first: Elke

last: Hattingen

first: Karl

last: Plate

first: Yvonne

last: Reiss


title: Type I IFN impedes early bacterial control in TB-resistant and -susceptible mice and activates neutrophils to restrict lung macrophage-T cell interactions

status: Public on Sep 09 2025

city: London

first: Anne

last: O'Garra

address: 1 Midland Rd

institute: The Francis Crick Institute


title: Single cell RNA sequencing of heart cells in hypereosinophilia-associated heart disease model

city: Cincinnati

first: Nives

last: Zimmermann

state: OH

address: 231 Albert Sabin Way, CVC Room 1925

department: Pathology and Laboratory Medicine

institute: University of Cincinnati

summary: Cardiac complications in patients with hypereosinophilia cause significant morbidity and mortality. However, mechanisms of how eosinophilic inflammation causes heart damage are poorly understood. We developed a model of hypereosinophilia-associated heart disease by challenging hypereosinophilic mice with peptide from the cardiac myosin heavy chain. Disease outcomes were measured by histology, immunohistochemistry, flow cytometry, and measurement of cells and biomarkers in peripheral blood. Eosinophil dependence was determined by using eosinophil-deficient mice (DdblGATA). Single cells from heart were subjected to single cell RNA sequencing to assess cell composition, subtypes and expression profiles. Mice challenged with myocarditic and control peptide had peripheral blood leukocytosis, but only those challenged with myocarditic peptide had heart inflammation. Heart tissue was infiltrated by eosinophil-rich inflammatory infiltrates associated with cardiomyocyte damage. Disease penetrance and severity were dependent on the presence of eosinophils. Single cell RNA sequencing showed enrichment of myeloid cells, T-cells and granulocytes (neutrophils and eosinophils) in the myocarditic mice. Macrophages were M2 skewed, and eosinophils had an activated phenotype. Gene enrichment analysis identified several pathways potentially involved in pathophysiology of disease. In conclusion, eosinophils are required for heart damage in hypereosinophilia-associated heart disease. Additionally, myeloid cells, granulocytes and T-cell cooperatively or independently participate in the pathogenesis of hypereosinophilia-associated heart disease.

overall_design: Mice were challenged with control (C) or myocarditic (M) peptide, and heart single cell suspensions were subjected to scRNA sequencing.

first: Usman

last: Sunusi


title: Targeting myoferlin in ER/Golgi vesicle trafficking reprograms cancer-associated fibroblasts in pancreatic cancer.

status: Public on Aug 28 2025

city: Liège

first: Olivier

last: Peulen

address: Av Hippocrate 13

country: Belgium

institute: University of Liège

summary: Pancreatic cancer cells exploit vesicle trafficking proteins such as myoferlin to fuel tumor aggressiveness, yet the presence and function of myoferlin-dependent vesicles in cancer-associated fibroblasts (CAFs) remain unknown. By combining PDAC whole-tumor and single-cell transcriptomic analyses with immunohistochemistry and 2D/3D in vitro models, we link stromal myoferlin to tumor aggressiveness. We identify CAF-specific functions of myoferlin, as MYOF-depleted CAFs present reduced activity and impaired extracellular matrix (ECM) production. Analysis of intracellular vesicles identifies a TGFß-receptor 1 (TGFBR1) trafficking blockade at the ER/Golgi interface upon myoferlin depletion, leading to altered TGFBR1 activation, impaired signal transduction, loss of ECM production and reduced CAF contractility. The genetic depletion of myoferlin in the murine tumor stroma and the pharmacological targeting of myoferlin alike reduced tumor desmoplasia in orthotopic KPC mice. Overall, we propose TGFBR1 trafficking as innovative target to reprogram CAFs, control desmoplasia and tackle these aggressive features in pancreatic cancer.

overall_design: Human PDAC CAFs originating from 4 donors were transfected with irrelevant (GL3) or myoferlin specific siRNA. Cells were collected 48h after cell transfection and submitted to bulk RNA-seq.

first: Raphaël

last: Peiffer

first: Gilles

last: Rademaker

first: Arnaud

last: Lavergne

first: Atsushi

last: Masamune


title: Bulk RNA-seq analysis of PDAC PANC-1 cells silenced with siRNA targeting myoferlin or treated with WJ460.

summary: Myoferlin is a transmembrane protein, encoded by the MYOF gene, initially identified in myoblasts for its crucial role in membrane biology via its C2 domain. MYOF was overexpressed in PDAC and functional studies have revealed myoferlin's critical involvement in mitochondrial adaptation, metatstasis and ferroptosis.

overall_design: PANC-1 cells were transfected with irrelevant (GL3), myoferlin specific siRNA or treated with myoferlin-targetting compound (WJ460, 50nM). Cells were collected 48h after cell transfection/treatment and submitted to bulk RNA-seq.


title: Music elicits different gene expression responses in the buccal cavity of age-related cognitive disorders patients and healthy controls.

city: Santiago de Compostela

first: Alberto

last: Gómez-Carballa

state: A coruña

address: Choupana sn

department: Pediatrics

country: Spain

institute: GENVIP research group

summary: Recent evidence suggests that external stimuli can shape transcriptomes (sensogenomics). Specifically, the analysis of capillary blood samples has shown that musical stimuli can modulate gene expression patterns, in healthy individuals but also in those with age-related cognitive disorders (ACD), based on. Here, we present groundbreaking evidence indicating that brief exposure to music can also imACDt the salivary transcriptome in both healthy donors and ACD patients. Our findings reveal that music has a more pronounced effect on patients compared to CONTROLrols, inducing global gene expression changes towards upregulation in ACD patients but downregulation in CONTROLrols. The most significantly dysregulated genes in ACD patients include LGALS3 (downregulated) and CXCL8 (upregulated), whereas in CONTROLrols, THOP1 was the top significant gene (downregulated). These genes play important roles in normal brain functions and are also altered in neurodegenerative conditions. Weighted Gene Co-expression Network Analysis reveals relevant and significant modules, both positive and negative correlated with music, implicated in neurodegenerative (e.g. autophagy) and immunological processes (e.g. IL-1, MHC). This sheds light on the complex interplay between music and molecular responses in the human body. This study underscores the potential of musical stimuli to influence gene expression patterns outside of systemic circulation, paving the way for further exploration of music’s therapeutic effects.

overall_design: We collected saliva samples at two timepoints: before and after an experimental concert of classical music. Saliva samples were collected in Oragene DNA devices (ORE-100; DNAgenotek), comprising 10 ACD patients (aged 84-92 years old; mean 84) and 14 healthy donors (aged 18-88; mean 57).

first: Antonio

last: Salas


title: Rescue of imprinted genes by epigenome editing in human cellular models of Prader-Willi syndrome

city: Shinjuku-ku

first: Akisa

last: Nemoto

state: Tokyo

address: 35 Shinanomachi

institute: Keio University School of Medicine

summary: Single cell gene expression profiling of PWS iPSC-derived hypothalamic organoids with and without epigenome editing. Raw data were not uploaded due to patient privacy concerns.

overall_design: Hypothalamic organoids at day 63-66 from epigenome-edited PWS iPSCs and unedited PWS iPSCs.

first: Kent

last: Imaizumi

first: Hirosato

last: Ideno

first: Hironobu

last: Okuno

first: Hideyuki

last: Okano


title: Long-read sequencing-based analyses of the adult Drosophila brain transcriptome in physiological and pathological settings

city: Providence

first: Bess

last: Frost

state: RI

address: 185 Meeting St

institute: Center for Alzheimer’s Disease Research, Brown University

summary: Optimal brain function requires that neurons carry out extensive post-transcriptional RNA processing to produce a vast diversity of transcripts. Accurate reconstruction and quantification of highly processed RNA using standard RNA sequencing approaches is challenging due to their short read lengths. Long-read direct RNA sequencing can resolve multiple variations within RNA isoforms by capturing full-length transcripts spanning multiple exon-exon junctions, repetitive regions (e.g. retrotransposons), and intronic structures. Here we produce an isoform-level map of post-transcriptional RNA modifications using Oxford Nanopore Technologies (ONT) long-read sequencing of native RNA strands extracted from heads of Drosophila melanogaster aged to day 10 of adulthood. In addition to identifying 930 transcripts that are not present in the reference transcriptome, we find that almost half of the total detected isoforms have polyadenylated tails in excess of 104 nucleotides and that over 59% of transcripts possessed detectable m6A-modified bases. RNA modifications are present in RNA transcribed from transposable elements, which are important drivers of genetic diversity and relevant to human neurodegenerative diseases, including Alzheimer’s disease and related tauopathies. Applying nanopore direct RNA sequencing to a Drosophila model of tauopathy with known transposable element activation and various types of errors in RNA handling reveals exceptionally diverse RNA processing events in regions that are considered difficult to characterize with traditional short-read sequencing. Taken together, we have uncovered complex transcript structures in adult Drosophila head in a physiological setting and in the context of tauopathy, laying the groundwork for future studies to characterize the diverse tau transcriptome in brain tissue from patients with Alzheimer’s disease and related tauopathies.

overall_design: Differential expression of transcripts between pooled control (elav-Gal4/+, n=3) and pooled tau (elav-Gal4/+;UAS-tauR406W/+, n=3) transgenic Drosophila heads was analyzed using Nanopore direct RNA sequencing. Pooled control heads (elav-Gal4/+, n = 6) were also sequenced with Illumina (n = 6) to compare the de novo isoform assemblies between long and short read libraries.

first: Paul

last: Ramirez

first: Gabrielle

last: Zuniga

first: Elizabeth

last: Ochoa


title: The contribution of the transcription factors Crz1 and Rim101 to the response to alkalinization in Komagataella phaffii

status: Public on Sep 02 2025

city: CERDANYOLA DEL VALLES

first: JOAQUIN

last: ARINO

state: Barcelona

address: ED. IBB

department: Biochemistry & Mol. Biol.

institute: UNIVERSITAT AUTONOMA BARCELONA

summary: In the industrially relevant yeast Komagataella phaffii, as in other yeasts, alkalinization of the medium results in fast and extensive transcriptional remodeling. This response has been useful to design novel methanol-free, regulatable platforms for heterologous protein expression. However, its molecular bases are fully unknown. Crz1 and Rim101/PacC are transcription factors known to contribute to the alkaline pH transcriptional responses in many fungi. We identified here the transcription factors Crz1 and Rim101 in K. phaffii and used CRISPR/Cas9 techniques to create single and double mutant strains. Phenotypic characterization shows that crz1 cells are strongly sensitive to Ca2+ ions, mildly sensitive to alkaline pH and hypertolerant to SDS. In contrast, rim101 cells are markedly hypersensitive to Na+ and Li+ ions, to alkaline pH and to SDS. RNA-seq transcriptomic analysis revealed that mutation of RIM101 affects 55% of genes whose expression is altered at pH 8.0, whereas lack of Crz1 alters only 11% of these. Thirty-eight genes are co-regulated by both Crz1 and Rim101. The PMC1 vacuolar Ca+2-ATPase is regulated by Crz1, whereas the ENA2 Na+-ATPase, the PHO89 and PHO84 phosphate transporters, and diverse genes involved in iron homeostasis are Rim101-dependent. These effects were confirmed by proteomic analyses after 3 h of alkalinization. Therefore, while Rim101 appears as a major player in the transcriptional response to alkalinization, nearly 40% of the alkaline pH transcriptional response in K. phaffii is controlled still unknown pathways.

overall_design: Comparison of mRNA levels by RNA-Seq between Komagataella phaffii yeast cells grown  on YP-glycerol at pH 5.5 (reference) and 8.0 (alkaline pH) for wild-type GS115 strain and cell mutated for PAS_chr3_0625 (RIM101) and PAS_chr2-2_0202 (CRZ1) transcription factors. Samples were taken after 0, 15, 30 and 60 min  upon alkalinization of the medium.

first: Joaquin

last: Arino

first: Marcel

last: Albacar

last: Casamayor

first: Asier

last: González


title: DNA topoisomerase I acts as supercoiling sensor for bacterial transcription elongation

status: Public on Aug 27 2025

city: Paris Cedex 05

first: Celine

last: Borde

address: 11 place Marcelin Berthelot

department: CIRB

country: France

institute: College de france

summary: During transcription, RNA polymerase (RNAP) continuously unwinds and rewinds DNA, generating negative and positive supercoils upstream and downstream, respectively. Using single-particle cryo-EM, we elucidated how bacterial RNAP and DNA Topoisomerase I (TopoI), which relaxes negative supercoils, operate in close spatial proximity. TopoI binds to relaxed DNA upstream of RNAP and this involves a conformational switch in the TopoI functional domains. This suggests that TopoI exerts a sensing role prior to the formation of negative supercoils. On DNA substrates mimicking negatively supercoiled DNA, TopoI threads one strand into the active site for cleavage and binds the complementary strand with an auxiliary domain. Transcriptomic and phenotypic analyses suggest that mutations affecting the conformational changes in TopoI impact gene expression and operon polarity in bacteria. In summary, we propose a comprehensive model for DNA relaxation in proximity of active bacterial transcription.

overall_design:
In order to study transcriptional changes when TopoI is partially depleted, an E. coli strain encoding a TopoI degradable by a Lon protease system from Mesoplasma florum was engineered and RNA-seq analysis was performed (mf-lon WT, 4h P.I. (AtC) and mf-lon TopA-PDT, 4h P.I. (AtC)).

To study transcriptional changes when TopoI variants are expressed, RNA-seq analysis was performed in a strain with TopoI depletion and CRISPR inhibition expressing TopoI variants (mf-lon TopoI-PDT CRISPRi pGB2-TopoI WT or variants (Gly5, G703P and Y704A)).

first: Olivier

last: Espeli


title: RNA-sequencing profiles of HepG2 cells overexpressing human constitutive androstane receptor (CAR)

city: Baltimore

first: Hongbing

last: Wang

address: 20 Penn Street

institute: University of Maryland, Baltimore

summary: The constitutive androstane receptor (CAR) is a nuclear receptor that plays a crucial role in regulating xenobiotic metabolism and detoxification, energy homeostasis, and cell proliferation by modulating the transcription of numerous target genes. CAR activation has been established as the mode of action by which phenobarbital-like nongenotoxic carcinogens promote liver tumor formation in rodents. This paradigm, however, appears to be unrelated to the function of human CAR (hCAR) in hepatocellular carcinoma (HCC). Here, doxycycline-inducible hCAR stable cells (HepG2-hCAR) were treated with vehicle control or doxycycline (1 μg/ml) for 72 hours. RNA samples were isolated using the miRNeasy Mini Kit (Qiagen) following the manufacturer’s instructions. Sequencing was carried out using the Illumina HiSeq 4000 according to the manufacturer’s instructions. Our results indicated that induced hCAR expression significantly upregulates 374 genes and downregulates 384 genes in HepG2 cells. These data provide a comprehensive transcriptomic resource for understanding CAR-mediated gene regulation in hepatoma cells and potentially offer new insights into its potential role in liver cancer.

overall_design: Compare the mRNA profiles of HepG2-hCAR cells after vehicle control and doxycycline  treatment, each sample was done in triplicate.

first: Zhihui

last: Li


title: Rac1 palmitoylation is required for cardiac stress adaptation and regulation of Protein Kinase A signaling

status: Public on Aug 21 2025

city: Ann Arbor

first: James

last: Teuber

state: MI

address: 1150 W Medical Center Dr

department: Pharmacology

institute: University of Michigan

summary: Cardiac hypertrophy is a common adaptation to cardiovascular stress and often a prelude to heart failure. We examined how S-palmitoylation of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), impacts cardiomyocyte stress signaling. Mutation of the cysteine-178 palmitoylation site impaired activation of Rac1 when overexpressed in cardiomyocytes. Cardiomyocyte-specific Rac1 conditional knock-in (Rac1cKI) mice expressing a Rac1C178S mutant protein exhibit normal cardiac structure-function but develop more severe cardiac hypertrophy in response to angiotensin-II (AngII) infusion, cardiomyocyte-specific overexpression of AngII type-I receptor (AT1R), and cardiac pressure overload. Moreover, pressure overload and AT1R overexpression evoked cardiac failure phenotypes in Rac1cKI mice not observed in controls. Mechanistically, Rac1cKI hearts and cardiomyocytes genetically-resistant to Rac1 S-palmitoylation have a profound increase in protein kinase A (PKA) substrate phosphorylation in response to acute b-adrenergic stimulation, as do Rac1cKI hearts subjected to chronic AngII treatment, AT1R overexpression, or pressure overload that correlates with more advanced heart failure phenotypes. This is not associated with increased PKA enzymatic activity, suggesting potential deficits in phosphatase activity at PKA-regulated phospho-sites. Taken together, this study suggests Rac1 S-palmitoylation dampens adrenergic drive and PKA-dependent modulation of the phospho-proteome in response to cardiovascular stress, revealing essential functions for S-acylated Rac1 in cardiac adaptation.

overall_design: Control (Rac1 cKI/cKI; --) and cardiomyocyte-specific Rac1 Cys178Ser knock-in mice (Rac1 cKI/cKI; Myh6-Cre) were treated with saline or AngII for 3 days or AngII for 14 days. Hearts were collected, RNA was isolated from mouse ventricular tissue and submitted for RNA sequencing.

first: Rachel

last: Scissors

first: Arasakumar

last: Subramani

first: Nageswara

last: Madamanchi

first: Matthew

middle: J

last: Brody


title: exoWNT3A/RSPO1 improves HE to LPC differentiation, hepatic organoids growth, and different acute and chronic liver injuries.

status: Public on Aug 20 2025

city: Guangzhou

first: Shixiang

middle: Clover

state: Guangdong

address: Guanzhou street

institute: Guangzhou national labratory

summary: Using human liver progenitor cell cultures, we showed that WNT3A and RSPO1 co-treatment could effectively regulate hepatic cell fate and uncovered their potential functional crosstalk with the PPARα signaling pathway. We also observed that dual ligands loaded on a single exosome (exoWNT3A/RSPO1) hyperactivated the WNT signaling and promoted efficient hepatic organoid growth compared to the small molecule inhibitor CHIR99021. After exoWNT3A/RSPO1 administration, we confirmed the efficient delivery and robust activation of WNT signaling in the mouse liver. Importantly, exoWNT3A/RSPO1 could accelerate liver repair and regeneration under various conditions, including acute and chronic injuries and aging-associated phenotypes.

overall_design: Libraries were constructed using RNA-seq technologies to obtain data on transcription.

first: Lingyan

last: Yang


title: Pan organ and time course analysis of T cells in acute LCMV (armstrong) infection (day 60) [I40]

status: Public on Aug 19 2025

city: Boston

first: Liang

state: MA

address: 77 Avenue Louis Pasteur

institute: Harvard Medical School

summary: This study is part of the immgenT Open Source Project, specifically from IGT40, which focuses on a pan-organ and time course analysis of T cells in acute LCMV (Armstrong) infection at day 60 post-infection. The dataset includes T cells isolated from multiple organs: spleen, prostate, submandibular gland, bone marrow, mesenteric lymph node, small intestine epithelium, small intestine lamina propria, lung, and mediastinal lymph node. 7-week-old male C57BL/6J mice infected intraperitoneally with 2×10^5 PFU LCMV Armstrong, and T cells were analyzed at 60 days post-infection (dpi). The study includes both endogenous T cells and adoptively transferred P14 and SMARTA TCR transgenic T cells. Mice received IV 100,000 SMARTA (CD45.1.2) and 50,000 P14 (CD45.1) T cells one day before infection.

overall_design: T cells were isolated from individual organs using mechanical dissociation, enzymatic digestion (collagenase I or DTE), and anti-CD45 intravenous labeling to distinguish tissue-resident from circulating cells. Sorted CD3e+ or IV- CD3e+ were profiled using single-cell RNA sequencing (10x Genomics), combined with CITE-seq (TotalSeq C) and paired TCR α/β sequencing. Samples were pooled using hashtags.

first: Giovanni

last: Galletti

first: Sara

last: Quon

first: Nicole

last: Scharping

first: Kennidy

last: Takehara

first: Amir

last: Ferry

first: Ananda

last: Goldrath


title: Transcriptomic and Epigenomic Profiling of MYADM and RhoA Regulatory Networks in Metastatic Cancer Models

city: taipei

first: Tai-Lung

last: Cha

state: taipei

address: 11490 No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 114, Taiwan (R.O.

department: National Institute of Cancer Research

country: Taiwan

institute: National Defense Medical Center

summary: This dataset comprises bulk RNA-seq and ATAC-seq profiles across multiple human and murine cell lines with diverse metastatic potentials to investigate the role of MYADM and RhoA in cancer progression. RNA-seq samples include MYADM and RhoA knockdown in murine breast cancer cells (4T1), MYADM overexpression in human mammary epithelial cells (MCF10A), and metastatic progression models derived from human kidney (ACHN) and lung (CL1 series) cell lines. Additionally, transcriptomic data were collected from bone marrow-derived monocytes isolated from wild-type and MYADM whole-body knockout mice. ATAC-seq data were generated from selected RNA-seq matched samples to characterize chromatin accessibility changes associated with MYADM and RhoA perturbation. All cells were cultured under standard conditions. This dataset provides insights into transcriptional and epigenetic alterations during MYADM- and RhoA-mediated cancer metastasis.

overall_design: We performed RNA-seq and ATAC-seq on cancer cell lines and monocytes to study the effects of MYADM and RhoA. Samples included MYADM/RhoA knockdown in 4T1 cells, MYADM overexpression in MCF10A, metastatic variants of ACHN, and CL1 lines, and monocytes from wild-type and MYADM knockout mice. All cells were cultured under standard conditions.

first: Yi-Ta

last: Tsai

first: En-Ting

last: Liu


title: Mapping Plasmodium transitions and interactions in the Anopheles female

status: Public on Aug 18 2025

first: Lisa

last: Verzier

address: 677 Huntington Avenue

department: Department of Immunology and Infectious Diseases

institute: Harvard University

summary: Gene expression during the late ookinete and oocyst stages of Plasmodium falciparum (human malaria parasite) development has not been previously described in detail. We used single-cell RNA-seq to map gene expression changes in both parasite and mosquito cells and their interactions at multiple timepoints after an infectious blood meal, and in control (dsGFP-injected) and EcR-depleted (dsEcR-injected) mosquitoes.

sample_organism:
Plasmodium falciparum
Anopheles gambiae

platform_organism:
Plasmodium falciparum
Anopheles gambiae

overall_design: Infected midguts were dissected from 80 dsRNA-injected female mosquitoes (dsGFP or dsEcR) and cellularlized by enzymatic digestion, purified and analyzed by single-cell RNA-seq (10X Genomics). Timepoints were 36 h, 2 d, 4 d, and 7 d post infectious blood meal. On-day old mosquitoes were injected with dsRNA 3 d prior to blood feeding.

first: Yan

last: Yan

first: Elaine

last: Cheung

first: Lisa H.

first: Duo

last: Peng

first: W. Robert

last: Shaw

first: Flaminia

last: Catteruccia


title: Pan organ and time course analysis of T cells in acute LCMV (armstrong) infection (day 7) [I36]

first: Liang

summary: This study is part of the immgenT Open Source Project, specifically from IGT36, which focuses on a pan-organ and time course analysis of T cells in acute LCMV (Armstrong) infection at day 7 post-infection. The dataset includes T cells isolated from multiple organs: spleen, prostate, submandibular gland, bone marrow, mesenteric lymph node, small intestine epithelium, small intestine lamina propria, lung, and mediastinal lymph node. 7-week-old male C57BL/6J mice infected intraperitoneally with 2×10^5 PFU LCMV Armstrong, and T cells were analyzed at 60 days post-infection (dpi). The study includes both endogenous T cells and adoptively transferred P14 and SMARTA TCR transgenic T cells. Mice received IV 100,000 SMARTA (CD45.1.2) and 50,000 P14 (CD45.1) T cells one day before infection.