title: Comparative transcriptome analysis of JAZ4 knock-out plants (jaz4-1) and Col-0 Arabidopsis thaliana plants.

city: Davis

first: Maeli

last: Melotto

state: CA

address: 549 Kleiber Hall Dr

department: Plant Sciences

institute: University of California - Davis

summary: Time point RNAseq analysis of jaz4-1  mutant vs Col-0 reveals dynamic JAZ4 mediated regulatory pathways.

overall_design: Arabidopsis thaliana (L. Heyhn.) seeds were sown directly onto soil (SunGro Horticulture Sunshine Mix #1) in tray plugs (3.5 x 3.5 x 5.5 cm) or pots (5 cm3). Plants were kept in growth chamber maintained at 22 degree C, with a 12-hour photoperiod, light intensity of 100 ± 20 µmol/m2/sec, and 60 ± 5% relative humidity. The wild type ecotype Columbia (Col-0, ABRC stock CS60000) and its derivative JAZ4 knockout mutant jaz4-1 (SALK_141628C) were obtained from the Arabidopsis Biological Resource Center (ABRC). Three week old rosette shoots were collected at six-hour increments starting at dawn and spanning 18 hours (ZT 0, 6, 12, and 18). Three biological replicates were sampled, each containing six rosettes that were cut at the hypocotyl region, immediately frozen in liquid nitrogen, and stored at -80oC until the time for tissue processing.

first: Zachariah

last: Jaramillo


title: RNA sequencing of mouse cardiac neutrophils after myocardial ischemia and reperfusion injury model

status: Public on Jun 28 2025

city: Tsukuba

first: Chigusa

last: Nakahashi-Oda

state: Ibaraki

address: 1-1-1 Tennodai

department: Immunology

country: Japan

institute: University of Tsukuba

type: Expression profiling by high throughput sequencing

summary: We performed bulk RNA-seq of cardiac neutrophils from the heart of WT and Cd300a-/- mice 3 days after  myocardial ischemia and reperfusion.

overall_design: CD45.2+ CD11b+ Ly6G+ SiglecF+ neutrophils and CD45.2+ CD11b+ Ly6G+ SiglecF- neutrophils were isolated using flow cytometry from heart of WT and Cd300a-/- mice 3 days after Myocardial ischemia and reperfusion. Eight hearts were pooled per each sample.

first: N

last: Nishiyama

first: T

last: Sugasawa

first: C

first: A

last: Shibuya


title: PANAD/C7orf25 interacts with NXF1 to promote CDK6 mRNA nuclear export and G1/S transition

status: Public on Jun 27 2025

city: Guangzhou

first: huanhui

last: feng

address: Xin Gang Xi Road 135#

country: China

institute: Sun Yat-sen University

summary: Nuclear export factor 1 (NXF1) exerts mRNA transporter activity via binding to adaptors. We aimed to identify new NXF1 adaptors, and found that the R122/E125/G133/D139 amino acid residues of C7orf25 interacted with the Q20/K22/K23 residues in the RBD domain of NXF1, which disrupted the intramolecular interaction between the RBD and NTF2L domains of NXF1, consequently enhancing the binding of NXF1 to target mRNAs and promoting mRNA nuclear export. Furthermore, C7orf25 accelerated the G1/S transition and promoted tumor cell growth via interacting with NXF1 to promote nuclear export of CDK6 mRNA. The levels of C7orf25, NXF1, and CDK6 proteins were elevated in human hepatocellular carcinomas, and high C7orf25 levels were associated with worse survival. These findings identify C7orf25, which we named PANAD (Proliferation-Associated NXF1 Adaptor), as a novel NXF1-interacting adaptor and disclose the crucial roles of PANAD/C7orf25 in mRNA nuclear export and tumor growth, which provides potential target for cancer therapy.

overall_design: Human hepatoma cell lines, HepG2 and SNU-449 were transfected with NC or siPANAD-1/2 for 48 h and then isolated their cytoplasmic and nuclear fraction. RNA was isolated from the cytoplasmic and nuclear extracts using Trizol reagent. RNA Sequecing was performed  in biological duplicates.

first: Jin-Yu

last: Liu

first: Huan-Hui

last: Feng

first: Shi-Mei

last: Zhuang


title: Fundamental mechanisms causing pituitary stem cell aging in mice and humans

city: Stony Brook

first: Leonard

middle: YM

last: Cheung

state: New York

address: 101 Nicolls Road

country: USA

institute: Stony Brook University

summary: The pituitary gland produces hormones that are required to maintain proper endocrine function throughout adult life, but organ function declines with age.  In particular, pituitary stem cells lose their ability to regenerate hormone-producing cells in response to organ damage by middle age in mice.  In this proposal, we will use cutting edge single-cell RNA sequencing and human induced pluripotent stem cell techniques to determine genes responsible for pituitary stem cell aging in hopes of prolonging the window of regeneration in vivo.

overall_design: single-nuclei RNAseq of 4 pools of pituitary nuclei. Each pool is made of 3 individual mouse pituitary glands. The 4 pools are male and female, 5 and 22-month-old UM-HET3 wild-type mice.


title: Systematic disruption of zebrafish fibrillin genes identifies a translational zebrafish model for Marfan syndrome

city: Ghent

first: Karo

last: De Rycke

address: Corneel Heymanslaan 10

country: Belgium

institute: Ghent University

summary: Fibrillin dysfunction in Marfan syndrome (MFS) causes severe cardiovascular complications, including aortic dilation, dissection, and rupture. To model MFS, we generated zebrafish mutants lacking various fibrillin genes. Among them, fibrillin-2b-deficient zebrafish exhibited cardiovascular phenotypes resembling those seen in patients with MFS. Multimodal imaging revealed early cardiac defects, bulbus arteriosus dilation, and valve abnormalities. RNA sequencing identified developmental disruptions, and compound testing demonstrated the model’s potential for drug discovery. This zebrafish model, recapitulating key cardiovascular features of MFS, provides a valuable platform for investigating disease mechanisms and identifying novel treatment strategies.

overall_design: Bulk RNA-sequencing on whole fbn2b-/- and WT control embryo's at 1 and 2 dpf, to identify early transcriptional changes during the development of the first cardiovascular phenotypes.

first: Marina

last: Horvat

first: Lisa

last: Caboor

first: Griet

last: De Smet

first: Marta

last: Santana Silva

first: Wouter

last: Steyaert

first: Matthias

last: Van Impe

first: Patrick

last: Segers

first: Julie

last: De Backer

last: Sips


title: Melanoma cell lines: generated from pre vs generated post anti-PD-1 therapy

city: chiba city

first: Kazuhiro

last: Aoyama

state: Chiba

address: 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan

institute: chiba university

summary: MEL02-1 and MEL02-2 are melanoma cell lines derived from a melanoma patient. MEL02-1 was  established from a pre-treatment metastatic lesion. MEL02-2 was established from post-treatment regressing lesion.

overall_design: Comparison of the two cell lines, MEL02-2 vs MEL02-1.

first: Takashi

last: Inozume


title: High-avidity Cathepsin G specific CAR-T cells for the treatment of Acute Myeloid Leukemia

city: Chapel Hill

first: Office of Genomics Research

last: UNC Lineberger Comprehensive Cancer Center

state: NC

address: 125 Mason Farm Road, CB #7599 5105-5106 Marsico Hall

institute: University of North Carolina at Chapel Hill

summary: Chimeric antigen receptor (CAR) T cells specific for myeloid-associated antigens expressed on the cell surface of acute myeloid leukemia (AML) cause depletion of normal myeloid progenitor cells. We developed a CAR specific for a human Leucocyte Histocompatibility Antigen (HLA)-A*02:01-restricted peptide of the cathepsin G protein, which is a myeloid-restricted protein expressed in the cytoplasm of myeloid leukemic blasts. Cathepsin G-specific CAR (CG1.CAR) T cells were further engineered to increase their functional avidity. Specifically, we developed CG1.CAR-T cells co-expressing the lymphocyte-specific protein tyrosine kinase (LCK) and duplicated CD3ζ chain, which allows the functional recognition of the CG1 peptide as low as 0.025 µM. Optimized CG1.CAR T cells displayed antileukemia effects in vitro and in vivo in AML patientderived-xenotransplant (PDX) mouse models and did not cause hematopoietic toxicity in colony assays and humanized mice. Mechanistically, LCK overexpression in CG1.CAR-T cells caused transcriptional modifications characterized by the overexpression of mitochondrial-encoded electron transport chain components that were correlated with increased mitochondrial mass and improved respiratory capacity. Based on these data, CG1.CAR-T cells hold clinical potential for the treatment of AML.

overall_design:
To investigate the effect of LCK overexpression on CAR signaling, we performed transcriptomic profiling of CAR-T cells following antigen stimulation. Human PBMCs were transduced with either CAR.CG1 or CAR.CG1.ζζ.LCK constructs and expanded for 10 days in the presence of IL-7 and IL-15. On day 10, cells were rested for 24 hours in cytokine-free medium. On day 11, CAR-T cells were co-cultured with U937/HLA-A2 tumor cells at an effector-to-target (E:T) ratio of 1:1 (0.5 × 10⁶ cells per condition). Co-culture was maintained for either 24 hours or 5 days. CAR-T cells were sorted by flow cytometry based on expression of the HA tag incorporated in the CAR constructs. RNA was extracted for sequencing at three time points: (1) prior to antigen stimulation (baseline), (2) 24 hours post-stimulation, and (3) 5 days post-stimulation. Samples from both CAR.CG1 and CAR.CG1.ζζ.LCK groups were included at all time points.

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

first: Tara

last: Walhart

first: Feifei

last: Song

last: Biondi

first: Simone

last: Stucchi

first: Guangming

last: Li

last: Peishun

first: Kyogo

last: Suzuki

first: Elizabeth

middle: G

last: Hunt

first: Andrew

last: Kennedy

first: Jessica

middle: E

last: Thaxton

first: Tracy

last: Withers

first: Laura

last: Herring

first: Courtney

last: Elliott

first: Sally

middle: A

last: Hunsucker

first: Rania

last: Tsahouridis

last: Serafini

first: Leah

last: Flick

first: Eben

middle: I

last: Lichtman

first: Mark

last: Woodcock

first: Lishan

last: Su

first: Zhiyuan

last: Yang

first: Guangyan

last: Xiong

first: Ziyou

last: Cui

first: Pei

last: Wang

first: Cheng

first: Barbara

last: Savoldo

first: Paul

middle: M

last: Armistead

first: Gianpietro

last: Dotti


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

city: Baltimore

first: Hangnoh

middle: Joseph

last: Lee

state: MD

address: 670 W Baltimore St

institute: University of Maryland School of Medicine

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

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

first: Yun

last: Li

first: Junfang

last: Wu


title: LAG3 marks activated but hyporesponsive NK cells

first: Marie

last: Marotel

state: ON

address: 2 143 Eccles Street

department: Cancer Research

country: Canada

institute: Ottawa Hospital Research Institute

summary: Natural Killer (NK) cells are critical for immunosurveillance. However, NK cells can become dysfunctional in contexts such as chronic stimulation by viral infections or cancer. NK cells often display an increased expression of immune checkpoint proteins (ICP) following chronic stimulation, and ICP blockade therapies are currently being explored for several cancer types, which have remarkable patient benefits. Nevertheless, the nature of ICP expression in NK cells is still poorly documented. In this study, we aimed to identify the phenotype of immune checkpoint LAG3 (Lymphocyte-activation gene 3) expressing NK cells. Using various experimental models (inflammation triggered by poly (I:C), cytokine treatment, Eµ-myc spontaneous lymphoma model and MCMV infection), we found that LAG3 is expressed by murine NK cells upon activation in different contexts, including in response to cancer and acute viral infections. We then sought to define the molecules features of NK cells expressing LAG3. LAG3 marks a subset of immature, proliferating and activated cells, which, despite activation, have a reduced capacity to respond to a broad range of stimuli. Further characterization also revealed that LAG3+ NK cells exhibit a transcriptional signature similar to that of exhausted CD8+ T cells. Taken together, our results support the use of LAG3 as a marker of dysfunctional NK cells across diverse chronic and acute inflammatory conditions.

overall_design: RNA seq profiling of LAG3+ and LAG3- murine CD11b+ NK cells that were FACS sorted from the spleen of C57BL/6 mice two days after poly (I:C) injection. Each replicate come from a pool of 10 spleens.

first: Valeria

last: Vasilyeva

first: Olivia

last: Makinson

first: Cynthia

last: Chan

first: Maria

last: Park

first: Colin

last: O’Dwyer

first: Ayad

last: Ali

first: Abrar

last: Ul Haq Khan

first: Christiano

last: Tanese de Souza

first: Mohamed

middle: S

last: Hasim

first: Sara

last: Asif

first: Reem

last: Kurdieh

first: John

last: Abou-Hamad

first: Edward

last: Yakubovich

first: Jonathan

last: Hodgins

last: Al Haddad

first: Giuseppe

last: Pietropaolo

first: Julija

last: Mazej

first: Hobin

last: Seo

first: Quitong

last: Huang

first: Sarah

last: Nersesian

first: Damien

last: Chay

first: Nicolas

last: Jacquelot

first: David

last: Cook

first: Seung-Hwan

last: Sciumè

first: Stephen

last: Waggoner

first: Michele

last: Ardolino


title: RNA-Seq of Bovine Precursor Adipocytes

city: Yinchuan

first: Lan

last: Feng

address: West Helan Mountain Road.XixiaDistrict,Yinchuan,China

department: College of Animal Science and Techology

institute: Ningxia university

summary: The HGFAC gene was subjected to deletion and acquisition assays, respectively, and RNA-Seq was performed in bovine precursor adipocytes transfected with si-NC, si-HGFAC, pcDNA3.1-NC, and pcDNA3.1-HGFAC, respectively, and by comparing the groups of si-NC, pcDNA3.1-NC, si-HGFAC, and pcDNA3.1-HGFAC, respectively, the si-HGFAC, pcDNA3.1-HGFAC and pcDNA3.1-HGFAC groups were identified. HGFAC, 46 and 130 differentially expressed genes were identified, respectively. Among them, in the si-HGFAC group, 33 genes were up-regulated and 13 genes were down-regulated; in the pcDNA3.1-HGFAC group, 27 genes were up-regulated and 103 genes were down-regulated, and the screened differentially expressed genes were subsequently analyzed by GO and KEGG.

overall_design: Interference assay: Bovine precursor adipocytes were subjected to transfection assay, divided into NC group and si group, with three replicates in each group. 48h after transfection, the cells were collected by Trizol, frozen and sequenced. Overexpression assay: bovine precursor adipocytes were transfected with pcDNA3.1, divided into pcDNA3.1-NC group and pcDNA3.1-HGFAC, three replicates in each group, 48h after transfection, cells were collected by Trizol, frozen and sequenced.

first: Yun

last: Ma


title: Mislocalization of mitochondrial DNA and subcellular RNA is a convergent mechanism in neurodegenerative dementias and is rescued by VCP ATPase inhibition

city: London

first: Christy

last: Hung

address: Gower St, London WC1E 6BT

country: United Kingdom

institute: UCL

summary: Nucleocytoplasmic transport defects have been observed in Alzheimer’s disease (AD) and frontotemporal dementia (FTD). However, there have been few systematic efforts to evaluate transcriptome-wide subcellular mRNA distribution in these conditions, which if deregulated may significantly compromise cellular homeostasis. Here, we assessed mRNA nucleocytoplasmic localization by performing transcriptome-wide profiling on nuclear and cytoplasmic fractions of human iPSC-derived cortical neurons from healthy individuals compared to those from both familial AD and FTD patients. Our findings revealed that AD and FTD mutations induce significant changes in mRNA nucleocytoplasmic distribution. We additionally reveal the redistribution of mitochondrial-related transcripts across different mutations. The significant ‘leakage’ of mitochondrial RNA (mtRNA) into the cytosol in AD and FTD mutant neurons motivated us to examine the leakage of mtDNA. Importantly, we found abnormal cytoplasmic accumulation of mtDNA in AD and FTD cortical neurons, which is reversible with treatment using a pharmacological inhibitor of the VCP D2 ATPase domain.

overall_design: Induced pluripotent stem cell derived motor neurons from controls, APP mutant, PSEN1 mutant and VCP MUTANT underwent subcellular fractionation into nuclear and cytoplasmic fractions. Cultures were treated with VCP D2 ATPase inhibitor ML240.

first: Miriam

last: Llorian

first: Rickie

last: Patani


title: Single nucleus RNA sequencing and functional in vivo studies reveal TCF21 as a protective regulator in cardiac fibrosis

city: Goettingen

first: Tousif

last: Azmain

state: State...

address: Robert Koch Street 40

department: Cardiology and Pneumology

country: Germany

institute: Georg August University

summary: Cardiac fibrosis is the hallmark underlying variosus forms of heart disease including aortic stenosis, contributing significantly to disease progression and mortality. However, the molecular mechanistic details remain largely unknown. We conducted single nucleus RNA sequencing (snRNA-seq) on human fibrotic AS and non-failing donor heart samples to track pathological changes at single-cell resolution and to identify cell-specific candidate genes involved in cardiac fibrosis.

overall_design: RNA expression profiling of aortic stenosis patient and non-failing control heart (left ventricle) biopsies by single-nucleus-sequencing

first: Hai

last: Doan


title: Transcriptomic analysis of ApoE-KO/APOL1 mouse choroid plexus

city: Bethesda

first: Teruhiko

last: Yoshida

state: Maryland

address: 10 Center Drive, 9N208

department: NIDDK - KDB

institute: National Institutes of Health

summary: We analyzed transcriptomic profiles of mouse choroid plexus by single-nuclear RNA-seq.

overall_design: Mouse choroid plexus samples (genotypes: ApoE-KO,  ApoE-KO/APOL1-G1) were snap frozen. Nuclear preparation from frozen choroid plexus and single-nucleus RNA-seq were conducted.

first: Shashi

last: Shrivastav

first: Jeffrey

middle: B

last: Kopp


title: The NuRD-SWI/SNF antagonism regulates the coordinated activation of EMT and inflammation in oral cancer

city: Rotterdam

first: Mathijs

last: Verhagen

address: Doctor Molewaterplein 40

country: Netherlands

institute: Erasmus Medical Center

summary: Phenotypic plasticity and inflammation, two well-established hallmarks of cancer, play key roles in local invasion and distant metastasis by enabling rapid adaptation to dynamic micro-environmental changes. Here, we show that in oral squamous carcinoma cell carcinoma (OSCC), the competition between the NuRD and SWI/SNF chromatin remodeling complexes plays a pivotal role in regulating both epithelialmesenchymal plasticity (EMP) and inflammation. By genetically perturbing both complexes, we demonstrate their opposing downstream effects on inflammatory pathways and EMP regulation. In particular, downregulation of the BRG1-specific SWI/SNF complex deregulates key inflammatory genes such as TNF-α and IL6 in opposite ways when compared with loss of CDK2AP1, a key member of the NuRD complex. We show that CDK2AP1 genetic ablation triggers a pro-inflammatory secretome encompassing several chemo- and cytokines thus promoting the recruitment of monocytes into the tumor microenvironment (TME) and their differentiation into M2c macrophages, as also validated on tumor microarrays from OSCC patient-derived tumor samples. Further analysis of the inverse correlation between CDK2AP1 expression and TME immune infiltration revealed specific downstream effects on CD68+ macrophage abundance and localization. Our study sheds light on the role of chromatin remodeling complexes in OSCC locoregional invasion and points at the potential of CDK2AP1 and other members of the NuRD and SWI/SNF chromatin remodeling complexes as prognostic markers and therapeutic targets.

overall_design: Gene expression profiling of oral squamous cell carcinoma (OSCC) cell lines w/wo CDK2AP1 knockout

first: R

last: Stabile

last: Fodde

first: F

last: Tucci

first: M

middle: P


title: Skeletal muscle mitochondria contain nuclear-encoded small and long RNA species prior to and following adaptation to exercise training in rats

city: Parkville

first: Adam

middle: James

last: Trewin

state: Victoria

address: Royal Pde

department: Anatomy and Physiology

country: Australia

institute: University of Melbourne

summary: Mitochondria import over 1000 proteins encoded by the nuclear genome, but the RNA contained within the organelle is generally thought to be only that which is transcribed from the mitochondrial genome. Recent evidence however suggests the presence of specific nuclear-encoded small- and long-non-coding RNAs (ncRNAs) in the mitochondrial matrix, hinting at a previously underappreciated level of subcellular, ncRNA-mediated regulation on mitochondrial function. The aim of this study was to characterise the population of RNAs contained within mitochondria isolated from rat skeletal muscle, and to investigate whether it was altered in response to endurance training, a potent metabolic stimulus that induces mitochondrial adaptations. Rats underwent four weeks of moderate intensity treadmill exercise training that induced typical adaptive responses at the transcriptome and functional levels in heart and skeletal muscle. Mitochondria from gastrocnemius skeletal muscle were isolated by immunoprecipitation, further purified, then sequenced to assess the mitochondrial transcriptome. Approximately 24 nuclear-encoded, coding or non-coding ‘long’ RNAs were detected in purified mitochondria, in addition to ~50 miRNAs with >100 normalised read counts. None were differentially expressed in the exercise vs control group at FDR < 0.05, but exploratory analyses (p<0.05) pointed towards 3 differentially regulated miRNAs in the mitochondria isolated from trained compared with sedentary muscle. In conclusion, we report the presence of a small population of nuclear-encoded long- and small RNAs in the mitochondria isolated from rat muscle tissue. Further research is required to investigate how these are imported into the mitochondria, and their role(s) in regulating exercise adaptations and mitochondrial biology

overall_design: Samples are ribo-depleted libraries construced from the total RNA of isolated mitochondria (MT) and the corresponding skeletal muscle (SM) whole tissue from sedentary-control (Sed) or exercise-trained (ExT) wistar kyoto rats. Libraries were also constructed from total RNA from the left ventricle (LV) whole tissue from a subset of animals.

middle: J


title: Simultaneous Targeting of Ovarian Cancer and Its Microenvironment Using Stem Cell-Engineered Off-The-Shelf CAR-NKT Cells

city: Los Angeles

first: Shuo

last: Li

address: 630 Charles E Young Dr S

institute: UCLA

type: Methylation profiling by high throughput sequencing

summary: Ovarian cancer (OC) poses a significant challenge due to frequent recurrence linked to tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). Targeting both OC cells and TME simultaneously holds promise for effective treatment. This study comprehensively analyzed 17 chemonaive and 18 refractory/recurrent OC samples, identifying mesothelin (MSLN) and natural killer receptor (NKR) ligands as tumor targets and CD1d as an OC TME target. Leveraging hematopoietic stem cell (HSC) gene engineering and feeder-free differentiation culture, we generated allogeneic MSLN-targeting CAR (MCAR)-engineered invariant natural killer T (MCAR-NKT) cells, demonstrating high-yield and high-purity production, potent antitumor efficacy, multiple tumor targeting mechanism, and significant in vivo expansion and persistence. Notably, these cells selectively deplete immunosuppressive TAMs and MDSCs, counteract tumor immune evasion, dispaly a favorable safety profile with low risks of GvHD and CRS, and exhibit a stable “hypoimmunogenic” phenotype attributed to epigenetic and signaling regulations. These findings underscore the preclinical feasibility and therapeutic potential of allogeneic MCAR-NKT cell products for OC, laying a foundation for translational and clinical development.

overall_design: 6 samples, including 3 allogeneic IL15-enhanced HSC-derived mesothelin-targeting CAR-engineered NKT (Allo15MCAR-NKT) cells, and 3 PBMC-derived MCAR-engineered T (MCAR-T) cells were included in this study. Genomic DNA was isolated from experimental samples using a QIAGEN DNeasy Blood & Tissue kit, then sonicated using a Covaris M220 Focused-ultrasonicator, following the manufacturers’ instructions. Then the genomic DNA was sent to UCLA TCGB core to conduct the WGBS library construction and sequencing.

first: Yan-Ruide

first: Zhe

first: Miao

first: Yuning

last: Chen

first: Lili

last: Yang


overall_design: Gene expression profiling of the CA1 cell line w/wo silencing of BRM and BRG1


title: Transcriptional differences in Bradyrhizobium sp. USDA 3456 during growth on methanol with La versus succinate with La

city: Berkeley

first: Charlotte

middle: Charlie

last: Mineo

address: 421 Koshland Hall

department: Plant and Microbial Biology

institute: UC Berkeley

summary: Nodule-forming bacteria play crucial roles in plant health and nutrition by fixing atmospheric nitrogen. Despite the importance of this relationship, how nodule-forming bacteria are affected by plant exudates and soil minerals is not fully characterized. Of particular interest are the effects of plant-derived methanol and lanthanide metals on the growth of nitrogen-fixing Rhizobiales. Prior work has demonstrated that select Bradyrhizobium are able to assimilate methanol only in the presence of lanthanide metals; however, the pathway enabling assimilation remains unknown. Here we characterize Bradyrhizobium sp. USDA 3456 to determine the pathways involved in methanol metabolism. Based on genomic analyses, we hypothesized that methanol assimilation in these organisms occurs via the lanthanide-dependent methanol dehydrogenase XoxF, followed by oxidation of formaldehyde via the glutathione-linked oxidation pathway, subsequent oxidation of formate via formate dehydrogenases, and finally assimilation of CO2 via the Calvin Benson Bassham (CBB) pathway. Transcriptomics revealed upregulation of the aforementioned pathways in Bradyrhizobium sp. USDA 3456 during growth on methanol. Assays demonstrated increased activity of the glutathione-linked oxidation pathway and formate dehydrogenases during growth on methanol compared to succinate. 13C-labeling studies demonstrate the presence of CBB intermediates and label incorporation during growth on methanol. Our findings provide multiple lines of evidence supporting the proposed XoxF-CBB pathway and, combined with genomic analyses, suggest that this metabolism is widespread among Bradyrhizobium and Sinorhizobium species.

overall_design: To identify genes involved in methanol metabolism, Bradyrhizobium sp. USDA 3456 grown in the presence of 10 µM lanthanum chloride with either succinate or methanol as a carbon source.  Cells were harvested during mid-exponential growth and RNA extraction and RNA-seq analyses were performed. Three replicates are provided for each condition.

middle: R

first: N

middle: C

last: Martinez-Gomez


title: Gut commensal Parabacteroides goldsteinii mitigates LRRK2 Parkinsonism by reducing neuroinflammation and enhancing gut homeostasis

city: Taipei

first: Jian-Da

last: Lin

address: No. 1, Sec. 4, Roosevelt Rd., Da'an Dist.

department: Department of Biochemical Science & Technology

country: Taiwan

institute: National Taiwan University

summary: Evidence suggests that Lewy body pathology in Parkinson's disease (PD) may originate in the gut, with intestinal inflammation serving as an early mediator via the gut-brain axis. Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common genetic risk factor for both PD and inflammatory bowel disease. We proposed that modulating the gut microenvironment could assist in mitigating PD progression, particularly in individuals with LRRK2 mutations. Our study indicates that germ-free condition could only partially alleviate PD process in LRRK2 G2019S mice. Mono-inoculation of PG in germ-free LRRK2 G2019S mice mitigated age-dependent motor dysfunction. In the brain, the colonic P. goldsteinii treatment reduces neuronal a-synuclein expression, ease neuroinflammation, and mitigates dopaminergic degeneration. In the gut, the PG administration suppressed the toll-like receptor 4 signaling, facilitated the differentiation of intestinal dendritic cells and macrophages, and increased the abundance of anti-inflammatory T cells. Our findings demonstrated that colonization by P. goldsteinii alleviates the progression of PD by exerting multifaceted effects in maintaining intestinal homeostasis.

overall_design: mouse model with the LRRK2 G2019S mutation was established. The intestinal commensal PG was orally administered to the 5-month-old mice to assess its impact on PD neuropathology. At 2.5 months (midterm) or 5 months (terminal) after PG inoculation, spatial and bulk RNA transcriptomics of brain samples and cytokine assays were conducted. Additionally, intestinal bulk and single-cell RNA sequencing, as well as cellular bioenergetic analysis, were performed to explore the gut immunomodulatory effects of PGon the PD process.


title: Microarray analysis reveals transcriptional differences in tobacco cells cultured without and with Al.

city: Kurashiki

first: Yoshiyuki

last: Tsuchiya

state: Okayama

department: Institute of Plant Science and Resources

institute: Okayama University

summary: Using our microarray data, we identified 1, 702 probes with known functions (661 upregulated and 1, 041 downregulated) with changes of at least 2-fold in their differential transcript levels with significance (P < 0.05) under Al treatment condition, compared with control condition in SL cells (note that some probes within the 1, 702 probes carry the same TIGR ID and/or UniGene ID). Microarray analysis of up- and down-regulated genes under Al exposure and following Gene Ontology (GO) enrichment analysis for biological process revealed only one GO term for the upregulated genes, ‘response to chitin’, annotated with genes coding MAP kinase (WIPK) and transcription factors (NtMYB3, NtERF1) but nine GO terms for the downregulated genes, including ‘cell wall loosening’ and ‘lipid transport’, annotated with genes coding expansins (NtEXPAs) and lipid transport protein (LTP) and LTP-like (NtLTP3, NtEIG-C29), respectively.

overall_design: Differential expression analysis between without (control) and with Al (100 µM AlCl3) under shaking condition, 3 different replicate of each treatments.

first: Yoko

last: Yamamoto


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

city: Edmonton

first: Serhiy

last: Havrylov

state: Alberta

address: 8-29 Medical Sciences Building

department: Medical Genetics

institute: University of Alberta

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

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

first: Ordan

last: Lehmann


title: Sequence-to-expression approach to identify etiological non-coding DNA variations in P53 and cMYC-driven diseases

city: Houston

first: Wenbo

address: 7000 Fannin Street

institute: The University of Texas Health Science Center at Houston

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Unraveling the immunological roles of murine serum amyloid A3 in aortic immune cell subsets during atherosclerosis progression

summary: Atherosclerosis is a growing concern in developed nations, necessitating the identification of therapeutic targets for advancing personalized medicine. Serum amyloid A3 (Saa3) has been linked to accelerated plaque progression by affecting cholesterol metabolism and modulation of inflammation. We hypothesize that knocking out Saa3 (Saa3-/-) could mitigate plaque development by regulating aortic immune cell subsetscompositions during atherosclerosis progression. Using a murine model, we induced atherosclerosis via a gain-of-function mutant PCSK9-encoding adeno-associated viral vector (AAVmPCSK9) in wild-type (WT) and Saa3-/- mice. Single-cell RNA sequencing revealed that Saa3-/- mice developed smaller plaques than WT mice, with and single-cell RNA sequencing revealed significant differences in aortic immune cell populations, particularly among aortic macrophages. Saa3-/-Trem2hi macrophages, characterized by high Gpnmb, Lpl, and Spp1 expressions, predominated over the typical resident foamy macrophages in WT mice.Saa3-/- compared to WT mice. SAA3 regulates cholesterol metabolism and inflammatory responses in foamy macrophages. Notably, aortic immune cells in atherosclerotic Saa3-/- mice also showed enhanced intercellular immune communication and increased signaling interactions, suggesting a shift towards an anti-inflammatory and tissue-repairing phenotype. Our study highlights the potential of Saa3 as a therapeutic target forkey modulator of aortic immune cells that impact atherosclerosis progression.

overall_design:
12-week-old Wild-type C57BL/6J mice wild-type (WT) and Saa3-/- littermates used for induction of murine atherosclerosis by injecting intraperitoneally once with AAVmPCSK9 (ssAAV8/hAAT-mPCSK9D377Y, AAV core, Institute of Biomedical Sciences, Academia Sinica, using a plasmid acquired from Addgene (Plasmid #58376) and kindly provided by Dr. Mi-Hua Tao) at 5×1011viral particles/mouse and fed on Western diet (Research Diets, Cat# D12079Bi) for 18 weeks. Single-cell RNA sequencing was then performed on the sorted aortic immune cells from atherosclerotic WT and Saa3-/- mice.

Bone marrow cells isolated from wild-type C57BL/6J mice were differentiated into bone marrow-derived macrophages (BMDMs) by culturing in RPMI 1640 with 10% heat-inactivated FBS, 1% P/S/A, and 20 ng/mL M-CSF for seven days. On day 7, adherent macrophages were detached and seeded into two groups: one left untreated (Control) and one treated with 100 ng/mL SAA3 for 24 hours. Single-cell RNA sequencing (scRNAseq) was then performed on both untreated and SAA3-treated BMDMs.


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

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

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


title: Claudin2 Upregulation: IBD and colitis-associated cancer [knockout]

city: Omaha

first: Dhundy

last: Bastola

state: NE

address: 1110 S 67th Street

institute: University of Nebraska at Omaha

summary: To investigate the role of claudin-2 in IBD and colitis-associated colon cancer

overall_design: Comparative gene expression profiling analysis of RNA-seq data for WT and Claudin-2 (knockout)

first: Amar

last: Singh


title: Claudin2 Upregulation: IBD and collitis-associated colon cancer [overexpression]

summary: To investigate the role of claudin-2 in IBD and collitis-associated colon cancer

overall_design: Comparative gene expression profiling analysis of RNA-seq data for WT and Claudin-2 (overexpression)

first: Singh

last: Amar


title: Claudin2 Upregulation: IBD and colitis-associated colon cancer


title: Sequence-to-expression approach to identify etiological non-coding DNA variations in P53 and cMYC-driven diseases [ChIP-seq]

summary: Most DNA variants associated with common complex diseases fall outside the protein-coding regions of the genome, making them hard to detect and relate to a function. Although many computational tools are available for prioritizing functional disease risk variants outside the protein-coding regions of the genome, the precision of prediction of these tools is mostly unreliable and hence not close to cancer risk prediction. This study brings to light a novel way to improve prediction accuracy of publicly available tools by integrating the impact of cis-overlapping binding sites of opposing cancer proteins, such as P53 and cMYC, in their analysis to filter out deleterious DNA variants outside the protein-coding regions of the human genome. Using a biology-based statistical approach, DNA variants within cis-overlapping motifs impacting the binding affinity of opposing transcription factors can significantly alter the expression of target genes and regulatory networks. This study brings us closer to developing a generally applicable approach capable of filtering etiological non-coding variations in co-occupied genomic regions of P53 and cMYC family members to improve disease risk assessment.

overall_design: ChIP-Seq analysis was conducted on untreated and treated Raji and U2OS cells with doxorubicin to identify genomic binding after treatment. Illumina HiSeq2500 platform in a 2x100bp paired-end configuration was used to obtain 15 million reads on average for each library sample.

first: Walid

last: Fakhouri

first: Lisha

last: Zhu

first: Jim

last: Zheng


title: The microbial metabolite imidazole propionate modulates hypothalamic activity and stress-induced behaviors

status: Public on Jun 26 2025

first: Xia

state: California

address: 610 Charles E. Young Drive East

department: Integrative Biology and Physiology

institute: University of California, Los Angeles

summary: Neural circuits driving mammalian behaviors are highly plastic and modulated by internal and external factors, including the gut microbiome. We identify imidazole propionate (ImP), a microbial metabolite linked to metabolic disorders, as a key modulator of brain activity and behavior. Bacterially derived ImP enters the systemic circulation and brain, where it alters neuronal gene expression and activity in the hypothalamus without inducing overt neuroinflammation. Elevating systemic ImP promotes stress-related pathways and disrupts GABAergic/glutamatergic signaling in the hypothalamus before peripheral glucose dysregulation occurs. Similarly, colonization with the ImP-producing bacterium Eggerthella lenta elevates behavioral and molecular features of stress. In a mouse model of type 2 diabetes, the gut microbiome exhibits an enhanced ability to produce ImP, leading to elevated systemic levels that are associated with heightened stress responses. In humans, higher ImP associates with reduced hypothalamic reactivity to food cues, impaired stress-coping, and increased emotional eating, mirroring the causal links between ImP, hypothalamic activity, and stress-related behaviors in mice. Overall, these findings establish ImP as a notable microbial metabolite that links gut dysbiosis to altered hypothalamic function and stress in metabolic disease.

overall_design: Conventional C57BL/6J mice  were treated with 350 μg imidazole propionate per day or vehicle i.p. by osmotic minipump for 2 weeks. The hypothalamus was then isolated for single-nucleus RNA sequencing.

first: Gulistan

last: Agirman

first: Michael

middle: N

last: Quicho

first: Xiaobei

last: Zhang

first: Jonathan

last: Lynch

first: Sung Min

last: Ha

first: Heidi

last: Schmidt

first: Kaden

last: Connelley

first: Angela

last: Liang

first: Kristie

last: Yu

first: Ezgi

last: Özcan

first: In Sook

last: Ahn

first: Cheng

last: Qian

first: Jorge

last: Paramo

first: Adriana

last: Espinoza

first: Thomas

middle: Q

last: de Aguiar Vallim

first: Arpana

last: Church

first: Elaine

middle: Y

last: Hsiao


title: Mechanistic Insights into 16'-DEC-Induced Autophagy and Its Implications for Hepatocellular Carcinoma Treatment

city: Shenzhen

first: haoqiang

last: Wan

address: 1066 Xueyuan Avenue, Nanshan District

institute: shenzhen university

summary: Hepatocellular carcinoma (HCC) is a malignant tumor with a high fatality rate, characterized by a poor prognosis and a low 5-year survival rate. Although significant progress has been made in immunotherapy and targeted therapy for HCC in recent years, the overall survival benefits for patients remain very limited. Therefore, the continuous development of new targets and the screening of specific therapeutic drugs are of great significance for further developing precise treatment methods, exploring more effective combination therapies, overcoming drug resistance. In our preliminary work 272 bioactive compounds have been isolated and identified from edible and medicinal traditional Chinese medicines including Lonicera japonica, Cistanche deserticola and Artemisia capillaris. Through systematic screening, we discovered that 16'-decarbomethoxydihydrovoacamine (16'-DEC), which derived from Tabernaemontana corymbosa, can significantly inhibit hepatoma cell viability and migratory capacity. Furthermore, 16'-DEC can act in combination with lenvatinib, an approved targeted drug for HCC, to further inhibit the proliferation of hepatoma cells in vitro and in vivo. Through transcriptome sequencing, we found that 16'-DEC significantly upregulated the autophagy-related signaling pathway. Mechanism studies have validated that 16'-DEC does induce autophagy in hepatoma cells, and blocking autophagy can significantly reverse the anti-tumor activity of 16'-DEC. Furthermore, we found that 16'-DEC inhibited the activation of the mTOR signaling pathway, and molecular docking experiments indicated that 16'-DEC had a high affinity for the mTOR protein. Biochemical kinase assays confirmed 16'-DEC as a direct mTOR inhibitor, suppressing its kinase activity with an IC50 0.83 μM in cell-free systems. Taken together, these results demenstated that 16’-DEC inhibited hepatocellular carcinoma through inducing autophagy by targeting the mTOR pathway, which make it a potential therapeutic agent for HCC.

overall_design: To further elucidate the molecular mechanisms underlying the anti-HCC activity of 16'-DEC, transcriptome sequencing was performed to analyze alterations in mRNA expression profiles in Huh7 cells following 16'-DEC treatment compared to the control group.

first: Haoqiang

first: Shuna

last: Liu

first: Xiaobin

last: Zeng

first: Boping

last: Zhou


title: Sustained Mesenchymal Reprogramming of Endothelial Cells after Completion of Chemotherapy [ChIP-seq]

city: Kansas City

first: Eugene

last: Konorev

state: MO

address: 1750 Independence Ave

institute: Kansas City University

summary: Cardiovascular disease is the prevailing cause of death among cancer survivors. Remarkable increase in cardiac disease burden in this group is likely due to the effects of cancer itself and, especially, cardiotoxic cancer treatments. Of the cardiotoxic cancer treatments, anthracyclines are notoriously known for causing vascular damage and severe cardiovascular complications. A defining feature of cardiac damage by doxorubicin (Dox), a prototypical anthracycline, is that it typically progresses after completion of chemotherapy. As the nature of delayed deterioration is not understood we focused in this study on the events that occur upon completion of chemotherapy. We adopted the Dox treatment/washout model to examine its lasting effects on endothelial cells. Our ChIP sequencing, transcriptomic, reporter plasmid, and Smad2/3 phosphorylation experiments demonstrated the enhanced activity of the canonical TGF-beta/activin pathway during Dox washout. Another notable feature was sustained mesenchymal reprogramming with significant upregulation of transcripts characteristic of fibroblastic and smooth muscle lineages. We utilized a selective ALK4/5/7 receptor kinase inhibitor, SB431542 (SB), to probe the role of the canonical TGF-beta/activin pathways in endothelial-to-mesenchymal reprogramming by Dox. When present during Dox washout, SB blocked increased expression of both mesenchymal transcripts and protein markers, and prevented cytoskeletal changes and fibronectin production by the treated endothelial cells. Cytoskeletal rearrangements led to increased endothelial monolayer permeability that was abolished by SB treatment. Thus, increased production of ALK4/5 receptor ligands, TGF-beta2 and activin, and heightened Smad2/3 activation response to these ligands during Dox washout leads to sustained mesenchymal reprogramming of endothelial cells and compromised endothelial barrier function.

overall_design: ChIP seq of Smad3 in human umbilical vein endothelial cells (HUVEC) after doxorubicin treatment followed by its washout.

first: Kass

last: Sjostrom

first: Shixin

last: Tao

first: Shannon

last: Landers

first: Amy

last: Kwok

first: Melissa

last: Cobb

first: Ria

last: Singh

first: Ralph

last: Shohet

first: Nataliya

last: Kibiryeva


title: The impact of GPT2 deficiency on gene expression in ovarian cancer cells

city: Hefei

first: Yifan

last: Feng

state: Anhui

address: Jixi Road 218

institute: The Anhui Medical University

summary: Here, functional experiments demonstrated that GPT2 significantly promotes ovarian cancer progression.RNA-seq analysis revealed that differentially expressed genes downstream of GPT2 are significantly enriched in the TNF signaling pathway, which was validated by Western blot.In summary, our data provide new molecular insights into ovarian cancer.

overall_design: The GPT2 SINC and PT2 SI A2780 ovarian cancer cell lines were used for 3v3 RNA-seq.

first: Min

last: Li


title: Sustained Mesenchymal Reprogramming of Endothelial Cells after Completion of Chemotherapy [RNA-seq]

summary: Cardiovascular disease is the prevailing cause of death among cancer survivors. Remarkable increase in cardiac disease burden in this group is likely due to the effects of cancer itself and, especially, cardiotoxic cancer treatments. Of the cardiotoxic cancer treatments, anthracyclines are notoriously known for causing vascular damage and severe cardiovascular complications. A defining feature of cardiac damage by doxorubicin (Dox), a prototypical anthracycline, is that it typically progresses after completion of chemotherapy. As the nature of delayed deterioration is not understood we focused in this study on the events that occur upon completion of chemotherapy. We adopted the Dox treatment/washout model to examine its lasting effects on endothelial cells. Our ChIP sequencing, transcriptomic, reporter plasmid, and Smad2/3 phosphorylation experiments demonstrated the enhanced activity of the canonical TGF-b/activin pathway during Dox washout. Another notable feature was sustained mesenchymal reprogramming with significant upregulation of transcripts characteristic of fibroblastic and smooth muscle lineages. We utilized a selective ALK4/5/7 receptor kinase inhibitor, SB431542 (SB), to probe the role of the canonical TGF-/activin pathways in endothelial-to-mesenchymal reprogramming by Dox. When present during Dox washout, SB blocked increased expression of both mesenchymal transcripts and protein markers, and prevented cytoskeletal changes and fibronectin production by the treated endothelial cells. Cytoskeletal rearrangements led to increased endothelial monolayer permeability that was abolished by SB treatment. Thus, increased production of ALK4/5 receptor ligands, TGF-2 and activin, and heightened Smad2/3 activation response to these ligands during Dox washout leads to sustained mesenchymal reprogramming of endothelial cells and compromised endothelial barrier function.

overall_design: RNA seq profiling of 1) human umbilical vein endothelial cells response to doxorubicin treatment; 2) human umbilical vein endothelial cells transcriptome change upon washout after doxorubicin treatment; and 3) response of control (scrambled shRNA) and Smad3 deficient (Smad3 shRNA) human cardiac microvascular endothelial cells to TGF-beta2 treatment.


title: Matric and osmotic stress have overlapping effects on Variovorax beijingensis transcription

first: Jonathan

middle: J.

last: Silberg

state: Texas

address: 6100 Main St

institute: Rice University

summary: Soil microbes must continuously adapt to changes in water availability, which dynamically fluctuates with weather and irrigation, and these adaptations are closely linked to climate effects. Soil water potential, which regulates microbe-available water, is controlled by both osmotic and matric potential, which both increase as soils dry. While both parameters can independently increase water potential, the genetic mechanisms of microbial response are unknown, with potentially different mechanisms available for microbes to respond to changes in soil osmolyte concentrations versus changes in water availability within a textured material. To explore microbial responses to matric versus osmotic potential shifts, we evaluated the activity, persistence, and transcription of Variovorax beijingensis in soils and liquid cultures subjected to either matrix or osmotic stress. We find this microbe respires in dilute minimal medium (-240 ±104 kPa), in liquid medium supplemented with sucrose (-1323 ±20.8 kPa), and in a pair of matrices that span a similar range of pressures (-183 ±55 and -1393 kPa ±200 kPa). Using principal-component analysis, we show that gene expression varies significantly across all four conditions, even in cases where the pressure is similar. However, the direction of gene expression changes arising from an increase in osmotic pressure within liquid medium and an increase in matric potential within the different soils covaried for 68% of the transcripts. Thus, as Variovorax transitions from conditions of low to high osmotic or matric potential, which both decrease water availability, there is large overlap in the transcriptional response, although the responses are not identical.

overall_design: V. beijingensis was grown in liquid mM9 (low osmotic potential), mM9 with 425 mM sucrose (high osmotic potential), artificial soil Q2 (low matric potential), and artificial soil M2 (high matric potential) for 72 hours in six replicates. The total RNA was extracted (followed by rRNA depletion), and the library was prepared for RNA-seq.

first: Jiwoo

last: Kim

first: Bjorn

last: Shockey

first: Kirsten

last: Hofmockel

first: Caroline

last: Masiello


title: PROLIFERATIVE STEM CELL LIKE POPULATION OF BLASTS IN KMT2A REARRANGED INFANT ALL

city: oxford

first: Thomas

last: Jackson

address: weatherall institute of molecular medicine

department: paediatrics

institute: University of Oxford

summary: Among pediatric acute lymphoblastic leukemias (ALL), KMT2A-rearranged infant ALL (KMT2Ar iALL) carries a uniquely poor prognosis due to high rates of treatment-refractory or relapsing disease. It is important to understand how KMT2A mutations drive such aggressive disease in order to develop more effective and less toxic therapies. The PROM1 gene, encoding the pentaspan glycoprotein prominin-1/CD133, is activated by the direct action of the most common KMT2A fusion protein; KMT2A::AFF1 (MLL-AF4). CD133 expression is essential for proliferation of KMT2A::AFF1+ cell lines but its role in primary disease remains unclear with heterogenous expression seen in iALL patient samples. To clarify the role of CD133 in KMT2Ar iALL we have used a highly physiological primary human fetal liver derived model (CRISPRKMT2A::AFF1 ALL) which recapitulates CD133 heterogeneity. We show that CD133 expression marks a highly proliferative subset of CRISPRKMT2A::AFF1 blasts with a stem-cell gene expression profile capable of causing more aggressive disease in vivo. CRISPR inactivation of PROM1 limits leukemic proliferation, suggesting a functional role in our model and providing a strong rationale for targeting therapies against CD133.

overall_design: RNA-seq of fetal derived MLL-AF4 iALL model

first: Joe

last: W Cross

first: Lucy

last: Field

last: Hamer

first: Alastair

last: Smith

first: Nicholas

last: T Crump

first: Siobhan

last: Rice

last: Harman

first: Rebecca

middle: E

last: Ling

first: Natalina

last: Elliott

first: Qinqing

last: Wu

first: Nouhad

last: El Ouazzani

last: Thomas

first: Sarah

last: Inglott

first: Jack

last: Bartram

first: Irene

last: Roberts

last: Milne

first: Anindita

last: Roy


title: Modulatory Role of Radioprotective 105 in Mitigating Oxidative Stress and Ferroptosis via the HO-1/SLC7A11/GPX4 Axis in Sepsis-mediated renal injury

city: wuhan

first: Hong

last: Duo

address: No. 169 East Lake Road, Wuchang District

institute: Zhongnan Hospital of Wuhan University

summary: Sepsis-associated acute kidney injury (SA-AKI) is a critical condition characterized by high morbidity and mortality rates, particularly in intensive care settings. This study focuses on RP105, a pattern recognition receptor, exploring its role in moderating the mechanisms of oxidative stress and ferroptosis during SA-AKI, offering insights into its potential as a therapeutic target. SA-AKI model was established using RP105 knockout (KO) and wild-type (WT) mice through cecal ligation and puncture (CLP). Comprehensive evaluations included the assessment of ferroptosis markers and the expression levels of pro-inflammatory cytokines. RP105 expression was markedly reduced in the kidneys following CLP induction, correlating with worsened renal outcomes. Compared to the Sham group, RP105-/- mice displayed heightened renal damage, increased levels of oxidative stress markers, and enhanced lipid peroxidation. Notably, the deficiency of RP105 led to increased macrophage infiltration and a shift towards pro-inflammatory phenotypes, which further potentiated ferroptosis and exacerbated renal tissue damage. By influencing macrophage behavior and mitigating inflammatory responses. RP105 deficiency exacerbates macrophage-induced inflammation, oxidative stress, and ferroptosis, forming a vicious cycle that leads to more severe renal injury. These findings underscore the pivotal role of RP105 in mitigating oxidative stress and suppressing ferroptosis in the context of SA-AKI through regulation of the HO-1/SLC7A11/GPX4 axis. By preventing macrophage polarization toward a pro-inflammatory phenotype, RP105 alleviates inflammatory responses and tissue damage, highlighting its potential as a therapeutic target. In contrast, RP105 deficiency exacerbates macrophage-driven inflammation, oxidative stress, and ferroptosis, creating a vicious cycle that worsens kidney injury. Thus, RP105 emerges as a promising therapeutic candidate for mitigating sepsis-induced renal damage.

overall_design: This dataset comprises RNA-seq data from six mouse kidney tissue samples collected from two experimental groups: Wild-type mice subjected to sepsis-induced injury via cecal ligation and puncture (CLP), and RP105 knockout mice subjected to CLP.  Each group included three biological replicates.

first: Yanwei

last: Yang

first: Jun

last: Luo

first: Yumeng

last: Cao

first: Qian

last: Liu

first: Jiarui

last: Zhang

first: Siqi

last: Du

first: Jian

last: You

first: Guqing

first: Qifa

last: Ye

first: Huaqin

last: Pan


title: Effect of vitamin D supplementation on liver transcriptome in pigs, estimated by 3`quant mRNA-seq

city: Balice

first: Anna

middle: Dominika

last: Steg

address: Krakowska 1

department: Department of Animal Molecular Biology

country: Poland

institute: National Research Institute of Animal Production

summary: We report the anaysis of the effect of the supplementation of pigs feed with high doses of vitamin D on the liver transcriptome. We observed significant changes in the expression of genes connected mostly to lipid metabolism.

overall_design: Animals were kept in individual straw-bedded pens with free access to water. At the 85th day of life, pigs were randomly assigned to one of 3 groups so that animals from one litter were divided among alll three groups. Pigs were fed with isoprotein and isoenergetic feeds differing only in the amount of vitamin D (0, 5000, 10000 IU/kg of feed). Experiment was continued for 90 days.

first: Maria

last: Oczkowicz

first: Małgorzata

last: Świątkiewicz


title: 9-cis-retinoic acid improves disease modelling in iPSC-derived liver organoids

city: Brussels

first: Stefaan

last: Verhulst

address: Laarbeeklaan 103, D022

department: BMWE

institute: Vrije Universiteit Brussel

summary: Liver fibrosis majorly impacts global health, necessitating development of in vitro models to study disease mechanisms and develop drug therapies. Relevant models should at least include hepatocytes and hepatic stellate cells (HSCs) and ideally use three-dimensional cultures to mimic in vivo conditions. Induced pluripotent stem cells (iPSCs) allow patient-specific liver modelling, but current models based on iPSC-derived hepatocytes (iHepatocytes) and HSCs (iHSCs) still lack key functions. We developed organoids of iHepatocytes and iHSCs, and compared them to HepaRG and primary HSC organoids. RNA-sequencing analysis comparison of these cultures identified a potential role for the transcription factor RXRA in hepatocyte differentiation and HSC quiescence. Treating cells with the RXRA ligand 9-cis-retinoic acid (9CRA) promoted iHepatocyte metabolism and iHSC quiescence. In organoids, 9CRA enhanced fibrotic response to TGF-β and acetaminophen, highlighting its potential for refining iPSC-based liver fibrosis models to more faithfully replicate human drug-induced liver injury and fibrotic conditions.

overall_design: RNA sequencing of primary human hepatocytes and hepatic stellate cells, iPSCs, iPSC-derived hepatic stellate cells and hepatocytes, and HepaRG cell lines.

first: Leo A.

last: van Grunsven

first: Vincent

last: Merens


title: Chemically-induced protein degradation reveals inflammation-dependent requirement for Treg lineage-defining transcription factor FOXP3

city: Vienna

first: Moritz

last: Gaidt

address: Campus-Vienna-Biocenter 1

country: Austria

institute: IMP

summary: Regulatory T (Treg) cells are immunosuppressive CD4 T cells defined by expression of the transcription factor FOXP3. Genetic loss-of-function mutations in Foxp3 cause lethal multi-organ autoimmune inflammation resulting from defects in Treg cell development and suppressive activity. Whether FOXP3 is continuously required to maintain existing Treg cells is still unclear, however. Here, we leveraged chemically-induced protein degradation to show that functionally suppressive Treg cells in healthy organs can persist in the near-complete absence of FOXP3 protein for at least 10 days. Conversely, Treg cells responding to type 1 inflammation in settings of autoimmunity, viral infection, or cancer were selectively lost upon FOXP3 protein depletion. Acute degradation experiments revealed that FOXP3 acts as a direct transcriptional repressor to modulate responsiveness to cytokine stimulation. This inflammation-dependent requirement for FOXP3 enabled induction of a selective anti-tumor immune response upon systemic FOXP3 depletion, without causing deleterious T cell expansion in healthy organs.

overall_design: totalRNAseq: To investigate nascent transcriptional changes after Foxp3 protein depletion, we performed totalRNAseq on FACS-sorted Treg cells from steady-state and inflamed Foxp3AID-V5-DTR-GFP Rs26Tir1(F74G) mice treated for 6h with either PBS or 5-Ph-IAA.

first: Christina

last: Jäger

first: Markus

last: Jaritz

first: Joris

last: van der Veeken

first: Polina

last: Dimitrova

first: Rene

last: Rauschmaier

last: Obenauf

first: Meinrad

last: Busslinger

first: Qiong

last: Sun

first: Elisa

last: Marchiori

first: Guillem

last: Estivill


title: Effect of depletion of Med23 on gene expression during VSV infection of MEF and BMDM cells.

city: Shanghai

first: zhang

last: yiyang

address: 2005 Songhu Road, Yangpu District, Shanghai, China

institute: Fudan

summary: The detection of cytosolic viral nucleic acids via pattern recognition receptors (PRRs) activates multiple signaling pathways, leading to the production of interferons (IFNs), which are essential for host survival during viral infection. Precise control of PRR gene expression is crucial for maintaining immune homeostasis. Here, we showed that Mediator complex subunit 23 (Med23) is required for the precise production of the innate immune receptor RIG-I in response to RNA virus infection. Med23 deficiency markedly enhances the production of type I IFNs, proinflammatory cytokines and IFN-stimulated genes (ISGs) in both multiple cell lines and primary macrophages infected with RNA viruses or stimulated with poly(I:C). Myeloid-specific Med23 knockout mice were generated to test the critical role of Med23 in host resistance to RNA virus infection in vivo. Mechanistically, Med23 interacts with the transcription factor forkhead box O3 (Foxo3) to negatively regulate RIG-I, thereby modulating IFN-I signaling. Collectively, these findings elucidate a previously unrecognized role of Med23 as a gatekeeper of the RIG-I-mediated antiviral innate immune response and suggest a potential target for controlling viral infection.

overall_design: To evaluate the transcriptome-wide role of Med23 in VSV-induced signaling pathways, we isolated total RNA from Med23ΔM BMDMs and their controls with or without VSV infection and conducted RNA sequencing.Similarly, we analyzed wild-type and Med23 knockout MEFs after VSV infection via RNA-seq.

first: Defei

last: Xiong

first: Yiyang

last: Zhang


title: Characterization of induced cohesin loop extrusion trajectories in living cells [4C-seq]

city: Utrecht

first: Peter

last: Krijger

address: Uppsalalaan 8

institute: Hubrecht Institute

summary: The cohesin complex shapes chromosomes by DNA loop extrusion, but individual extrusion trajectories were so far unappreciable in vivo. Here, we developed and validated TArgeted Cohesin Loader (TACL), a system enabling the strong activation of anchored loop extrusion from dozens of defined genomic sites in living cells. Studying their individual loop extrusion trajectories revealed that extruding cohesin-STAG2 stops not only at domain boundaries but at all flanking CTCF sites, engaging them in a complex transient looping network that supports intradomain contacts. Cohesin-STAG1 cannot associate with weak CTCF binding sites and fails to similarly support intradomain interactions. NIPBL-MAU2 remains associated with cohesin when stalled at looping CTCF sites, suggesting these factors may also be required for loop stabilization. TACL induces cohesin traffic jams and illegal loops with divergent CTCF sites, demonstrating that stalled cohesin can block extruding cohesin in vivo. Genes exposed to TACL-induced loop extrusion were collectively hindered in transcription and the underlying chromatin altered its accessibility and reduced its H3K27ac marks. Thus, by enabling the study of individual loop extrusion trajectories in vivo, we could assign new functions to players, identify new looping networks and uncover an interplay between loop extrusion, gene transcription and chromatin composition.

overall_design: 4C-seq  of eHAP1 cells carying 27 TetO platforms expressing TetR-MAU2 (TACL) or TetR-mCherry, with and without doxycycline treatment and/or depletion of RAD21, CTCF, PDS5A, WAPL, STAG2  using auxin treatment.

first: Ruiqi

last: Han

first: Yike

last: Huang

first: Michelle

last: Robers

first: Mikhail

last: Magnitov

first: Iwan

last: Vaandrager

first: Amin

last: Allahyar

first: Marjon

last: Verstegen

first: Kexin

first: Elzo

last: de Wit

first: Wouter

last: de Laat


title: Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing [RNA-seq]

city: New York

first: Hyein

middle: Sophia

last: Cho

state: NY

address: 430 E 67th St

department: Developmental Biology

institute: Memorial Sloan Kettering Cancer Center

summary: Embryonic development follows a sequence of events that is broadly conserved across species, yet the pace of development is highly variable. Compared to most other species, humans exhibit a slower pace that is largely recapitulated in in vitro stem cell models, suggesting a cell-intrinsic clock that tracks time. Using the directed differentiation of human embryonic stem cells (hESCs) into neuroectoderm as a proxy for developmental timing, we performed a whole-genome CRISPR-Cas9 screen and found that epigenetic factors MEN1 and SUZ12 modulate the speed of hESC neural differentiation. Genetic and pharmacological loss-of-function of MEN1 or SUZ12 accelerates the acquisition of neural fate by altering the balance of activating H3K4me3 and repressive H3K27me3 chromatin modifications at bivalent promoters and thereby priming a faster activation of developmental genes upon differentiation. The acceleration effect is also observed in definitive endoderm, cardiomyocyte, and neuronal differentiations. These results indicate that chromatin bivalency acts a general driver of human-specific timing across all major germ layers and developmental stages. Furthermore, our study uncovers a novel functional cooperation between MEN1 and SUZ12 as a key mechanism for the temporal regulation of developmental programs.

overall_design: Bulk RNA-seq study of hESC-derived neuroectoderm cells, NT, MEN1 KO, SUZ12 KO

last: Xu

first: Lorenz

last: Studer


title: EPA Transcriptomic Assessment Product (ETAP) for 3:3 Fluorotelomer carboxylic acid

city: RTP

first: Logan

last: Everett

state: North Carolina

address: 109 T.W. Alexander Dr

department: Office of Research and Development

institute: U.S. Environmental Protection Agency

summary: The EPA Transcriptomic Assessment Product (ETAP) utilizes a standardized short-term in vivo study design and data analysis procedures to develop transcriptomic-based reference values for data poor chemicals. This data set corresponds to a report following the ETAP standard methods to derive a transcriptomic point of departure for 3:3 Fluorotelomer carboxylic acid (3:3 FTCA). More information about the ETAP program is available here: https://www.epa.gov/etap

overall_design: A 5-day repeated dose exposure study for 3:3 FTCA was performed in both male and female rats separated into 8 dose groups plus vehicle control animals. Transcriptomic measurements were performed using targeted RNA sequencing in kidney, liver, adrenal gland, brain, heart, lung, ovary (females), spleen, testis (males), thyroid, thymus, and uterus (females). The resulting data was used as the basis for deriving the transcriptomic point of departure (POD) for 3:3 FTCA. The GO biological process class with the lowest median benchmark dose (BMD) value was identified across all the tissues examined in either sex.

first: Amanda

last: Brennan

first: Mike

last: DeVito

first: Alison

middle: H

last: Harrill

first: Michael

last: Hughes

first: Denise

last: Macmillan

first: Esra

last: Mutlu

first: Russell

last: Thomas

first: Leah

last: Wehmas

first: Chelsea

last: Weitekamp


title: EPA Transcriptomic Assessment Product (ETAP) for Perflurohexanesulfonamide

summary: The EPA Transcriptomic Assessment Product (ETAP) utilizes a standardized short-term in vivo study design and data analysis procedures to develop transcriptomic-based reference values for data poor chemicals. This data set corresponds to a report following the ETAP standard methods to derive a transcriptomic point of departure for Perflurohexanesulfonamide (PFHxSA). More information about the ETAP program is available here: https://www.epa.gov/etap

overall_design: A 5-day repeated dose exposure study for PFHxSA was performed in both male and female rats separated into 8 dose groups plus vehicle control animals. Transcriptomic measurements were performed using targeted RNA sequencing in kidney, liver, adrenal gland, brain, heart, lung, ovary (females), spleen, testis (males), thyroid, thymus, and uterus (females). The resulting data was used as the basis for deriving the transcriptomic point of departure (POD) for PFHxSA. The GO biological process class with the lowest median benchmark dose (BMD) value was identified across all the tissues examined in either sex.


title: Epigenetic attenuation of interferon signaling drives aging-related improvements in systemic lupus

city: San Francisco

first: Charles

last: Langelier

state: CA

address: HSE 401, 513 Parnassus Ave

department: Medicine

institute: University of California San Francisco

summary: In the general human population, aging is associated with a rise in systemic inflammation, primarily involving innate immune pathways related to interferon (IFN), toll-like receptor, and cytokine signaling. In systemic lupus erythematosus (SLE), a prototypical systemic autoimmune disease, aging is distinctly associated with improvements in disease activity, suggesting a unique relationship between aging and inflammation in this disease. Using a multi-omic approach incorporating transcriptional profiling, single cell RNA sequencing and methylation analysis, we studied age-related changes in the immune profiles of 287 SLE patients between 20 and 83 years old, and compared the results against 928 healthy controls aged between 21 and 89 years old. In contrast to the increase in inflammatory gene expression that occurs with aging in most healthy adults, SLE patients exhibited the opposite. Most notable was a decrease in type I and II IFN signaling that was evident across multiple cell types, with natural killer (NK), CD4+ effector memory T cells, and naïve B cells exhibiting the most significant differences. We found that aging in SLE patients was also associated with differential methylation of the genome. Notably, of the genes both downregulated and hypermethylated with older age, IFN-related genes were disproportionately represented, suggesting that age-related decreases in IFN signaling were driven in part by epigenetic silencing. Both SLE patients and healthy controls demonstrated age-related declines in naïve T cells and lymphoid progenitor cells, but only SLE patients demonstrated age-related increases in CD56-dim NK cells. Taken together, our work provides new insight into the phenomenon of inflammaging and the unique clinical improvement in disease activity that occurs in SLE patients as they age.

overall_design:
Comparing age-associated gene expression in patients with lupus versus controls

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Submitter states that missing raw files are due to patient privacy concerns.
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title: Characterization of induced cohesin loop extrusion trajectories in living cells [BrU-seq]

first: Peter

last: Krijger

overall_design: ChIPseq  of eHAP1 cells carying 27 TetO platforms expressing TetR-MAU2 (TACL) or TetR-mCherry, with and without doxycycline treatment and/or depletion of RAD21, CTCF, PDS5A, WAPL, STAG2  using auxin treatment.

first: Ruiqi

last: Han

first: Yike

last: Huang

first: Michelle

last: Robers

first: Mikhail

last: Magnitov

first: Iwan

last: Vaandrager

first: Amin

last: Allahyar

first: Marjon

last: Verstegen

last: Zhang


title: EPA Transcriptomic Assessment Product (ETAP) for 7:3 Fluorotelomer alcohol

first: Logan

last: Everett

summary: The EPA Transcriptomic Assessment Product (ETAP) utilizes a standardized short-term in vivo study design and data analysis procedures to develop transcriptomic-based reference values for data poor chemicals. This data set corresponds to a report following the ETAP standard methods to derive a transcriptomic point of departure for 7:3 Fluorotelomer alcohol (7:3 FTOH). More information about the ETAP program is available here: https://www.epa.gov/etap

overall_design: A 5-day repeated dose exposure study for 7:3 FTOH was performed in both male and female rats separated into 8 dose groups plus vehicle control animals. Transcriptomic measurements were performed using targeted RNA sequencing in kidney, liver, adrenal gland, brain, heart, lung, ovary (females), spleen, testis (males), thyroid, thymus, and uterus (females). The resulting data was used as the basis for deriving the transcriptomic point of departure (POD) for 7:3 FTOH. The GO biological process class with the lowest median benchmark dose (BMD) value was identified across all the tissues examined in either sex.

first: Mike

last: DeVito

last: Harrill


title: Characterization of induced cohesin loop extrusion trajectories in living cells  [ATAC-seq]

first: Kexin

first: Elzo

last: de Wit

first: Wouter

last: de Laat


title: Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.

first: Hyein

last: Cho

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

overall_design: Refer to individual Series


title: Premature cell senescence promotes vascular smooth muscle cell phenotypic modulation in atherosclerosis and after injury

city: Cambridge

first: Simon

middle: Richard

last: Andrews

state: Cambs

address: Babraham Research Campus

department: Science Services

institute: The Babraham Institute

summary: Human atherosclerotic plaque cells display DNA damage that can promote premature cell senescence. Vascular smooth muscle cells (VSMCs) predisposed to senescence promote atherogenesis and features of unstable plaques, and increase injury-induced neointima formation. However, how premature senescence promotes vascular disease is unknown. Two independent in vitro models of VSMC senescence induced a range of modulated VSMC phenotype markers, whose expression domains overlapped with senescence markers in atherosclerotic plaque scRNA-seq datasets of human and mouse VSMCs. Mice expressing a VSMC-restricted mutant telomere protein (TRF2T188A) increased expression of multiple de-differentiation genes in vivo in atherosclerosis and after injury, and pathways associated with extracellular matrix organisation, inflammation and Tgfb response. Trf2T188A VSMCs had defective Tgfb signaling and were resistant to Tgfb-induced re-differentiation. Our results suggest that VSMC senescence promotes atherosclerosis and neointima formation in part by driving inflammation and inhibiting re-differentiation of VSMCs.

overall_design: This entry contains data from 10X single-cell RNA-seq analysis of plaques from the aorta (root, arch) and carotid arteries of Trf2T188A/ApoE-/- and  ApoE-/- mice and 10X single-cell RNA-seq analysis of VSMCs from Sm22a-Trf2T188A (Trf2T188A) and wild-type control mice 28 days after carotid ligation

first: Martin

last: Bennett

first: Helle

middle: F

last: Jørgensen

first: Sebnem

last: Oc

first: Anuradha

last: Kaistha

first: Abel

middle: M

last: Garrido

first: Matthew

middle: D

last: Worssam

first: Maria

last: Imaz

first: James

last: Taylor

first: Anna

last: Uryga


title: Delineation of a thrombin receptor-stimulated vascular smooth muscle cell transition to a plaque-stabilising fibrous cap-associated state [bulkRNA]

last: Jorgensen

address: Papworth Road

department: Cardiorespiratory section

institute: University of Cambridge

summary: Aims: Vascular smooth muscle cells (VSMCs) accumulate in atherosclerotic plaques and exhibit remarkable phenotypic plasticity, contributing to both plaque growth and stability. The plaque-stabilising fibrous cap is rich in VSMC-derived cells, yet the cellular transitions and regulatory mechanisms governing fibrous cap formation remain unclear. We aimed to delineate the VSMC phenotypic transitions associated with this critical process. Methods and Results: Mapping of lineage-traced VSMCs during plaque development revealed investment of VSMCs prior to fibrous cap formation. Using single-cell RNA-sequencing (scRNA-seq) profiles of lineage-traced VSMCs from atherosclerotic and acutely injured mouse arteries, we identified a disease-specific VSMC state co-expressing contractile genes with extracellular matrix (ECM) components (including fibrillar collagens and elastin) and NOTCH3, which are associated with fibrous cap formation. Computational trajectory analysis predicted that this proposed fibrous cap-related VSMC (fcVSMC) state arises from a previously described plastic, intermediate VSMC population expressing SCA1 and VCAM1. Clonal analysis further showed that NOTCH3+ fcVSMCs derive from intermediate VSMCs in both atherosclerosis and an acute vascular injury model, suggesting a conserved disease-relevant mechanism. The fcVSMCs were enriched in plaque fibrous caps compared to lesion cores, consistent with a role in fibrous cap formation. By combining scRNA-seq trajectory analysis and spatial transcriptomics of human atherosclerotic plaques, we identified protease-activated receptor-1 (PAR1) as a candidate regulator of fcVSMC generation. PAR1 was expressed by VSMCs in human plaque fibrous caps and, functionally, PAR1 activation by thrombin induced expression of contractile genes and ECM components associated with the fcVSMC state in cultured human VSMCs. Conclusions: Our findings identify a VSMC transition linked to fibrous cap formation in atherosclerosis and show this is modelled by vascular injury. We identify VSMC-expressed PAR1 as a potential therapeutic target for promoting plaque stability by driving the transition to the matrix-producing, fibrous cap-associated VSMC state.

overall_design: To evaluate the transcriptional state induced by thrombin, we profiled gene expression in thrombin-treated and untreated cells using RNA-seq. This analysis was performed using cells from 3 female donors.

first: Matt

first: Jordi

last: Lambert


title: Biomarker Identification via Spatial Transcriptomics Profiling of Colorectal Cancer and Colorectal Cancer with Liver Metastasis Stem Cells

city: cheonan

first: Dongjun

last: Jeong

state: Chungcheongnam-do

address: 25, Bongjeong-ro, Dongnam-gu

country: South Korea

institute: Soonchunhayng Unvi.

summary: The survival rate of patients with colorectal cancer (CRC) declines sharply with recurrence and metastasis. Cancer stem cells play a crucial role in the initiation, progression, recurrence, and metastasis of colorectal cancer. Therefore, in this study, we aimed to identify the CRC-associated genes via spatial analyses of normal colon tissue, colorectal cancer tissue, and colorectal cancer liver metastasis using NanoString GeoMx digital spatial profiling.

overall_design: The TMA slide comprised 59 samples, including 40 cores of CRC (primary cancer), 10 cores of CRC with liver metastasis, and nine cores of normal colon tissue (adjacent to cancer). We selected samples from patients with CRC who had normal colon tissue, primary colorectal cancer tissue, and colorectal cancer with liver metastasis tissue. To identify tumors and cancer stem cells, CD44 and EpCAM staining was performed. EpCAM+/CD44- cells were used as markers to identify non-CRCSCs, and EpCAM+/CD44+ cells were used as markers to identify CRCSCs.

first: Jeong-An

last: Gim

first: Minho

last: Lee

first: Sooyoun

last: Kim


title: Characterization of induced cohesin loop extrusion trajectories in living cells [Hi-C]

first: Peter

last: Krijger

overall_design: HiC-contact profiles of eHAP1 cells carrying 27 TetO platforms expressing TetR-MAU2 (TACL) treated with or without doxycycline for 1 hour or TetR-mCherry.

first: Ruiqi

last: Han

first: Yike

last: Huang

first: Michelle

last: Robers

first: Mikhail

last: Magnitov

first: Iwan

last: Vaandrager

first: Amin

last: Allahyar

first: Marjon

last: Verstegen

first: Kexin

last: Zhang

first: Elzo

last: de Wit

first: Wouter

last: de Laat


title: Characterization of induced cohesin loop extrusion trajectories in living cells


title: Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing [ATAC-seq]

first: Hyein

last: Cho

overall_design: ATAC-seq study of human embryonic stem cells, NT, MEN1 KO, SUZ12 KO

last: Xu

middle: S

first: Lorenz

last: Studer


title: Delineation of a thrombin receptor-stimulated vascular smooth muscle cell transition to a plaque-stabilising fibrous cap-associated state

first: Helle

last: Jorgensen

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: This entry contains data from the following analyses: (1) 10X single-cell RNA-seq analysis of VSMC-lineage labeled cells isolated by flow-assisted cell sorting (FACS) from healthy control and and ligated left carotid arteries (11 days after surgery) of Myh11-EYFP animals. (2) 10X Visium spatial transcriptomic analysis of an early-stage human plaque from an aorta (54-year-old male).

last: Jørgensen

first: James

last: Taylor

first: Matt

last: Worssam

first: Sebnem

last: Oc

first: Jordi

last: Lambert

first: Martin

last: Bennett


title: Long-read RNA Sequencing of Human Meningiomas

status: Public on Jun 25 2025

first: Isabelle

last: Liu

department: Department of Biochemistry and Biophysics

institute: UCSF

summary: We report long-read Iso-Seq data of 84 meningiomas, which are used to differentiate patients with several metadata characteristics.

overall_design: Pacbio long-read Iso-Seq data of 84 human meningiomas.

first: David

last: Raleigh

first: Martha

last: Dwyer Cady

first: Benedict

last: Choi


title: Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing [CUT&RUN]

overall_design: CUT&RUN sequencing study of hESC-derived neuroectoderm cells, NT, MEN1 KO, SUZ12 KO


title: Single-cell multiomics reveals the oscillatory dynamics of RNA metabolism and chromatin accessibility during the cell cycle

city: Illkirch

first: Nacho

last: Molina

address: 1 Rue Laurent Fries

country: France

institute: Institut de génétique et de biologie moléculaire et cellulaire

summary: The cell cycle is a tightly regulated process that requires precise temporal expression of hundreds of cell cycle-dependent genes. However, the genome-wide dynamics of mRNA metabolism throughout the cell cycle remain uncharacterized. Here, we combined single-cell multiome sequencing, biophysical modeling, and  deep learning to quantify rates of mRNA transcription, splicing, nuclear export, and degradation. Our approach revealed that both transcriptional and post-transcriptional processes exhibit distinct oscillatory waves at specific cell cycle phases, with post-transcriptional regulation playing a prominent role in shaping mRNA accumulation. We also observed dynamic changes in chromatin accessibility and transcription factor binding footprints, identifying key regulators underlying the oscillatory dynamics of mRNA. Taken together, our approach  uncovered a high-resolution map of RNA metabolism dynamics and chromatin accessibility, offering new insights into the temporal control of gene expression in proliferating cells.

overall_design: Multiome profiling, snRNA-seq + snATAC-seq, of mouse embryonic stem cells culture in 2i and LIF in serum supplemented conditions

first: Maulik

middle: K

last: Nariya

last: Santiago-Algarra

first: Olivier

last: Tassy

first: Marie

last: Cerciat

first: Tao

last: Ye

first: Andrea

last: Riba


title: Characterization of induced cohesin loop extrusion trajectories in living cells [ChIP-seq]

first: Peter

last: Krijger

first: Ruiqi

last: Han

first: Yike

last: Huang

first: Michelle

last: Robers

first: Mikhail

last: Magnitov

first: Iwan

last: Vaandrager

first: Amin

last: Allahyar

first: Marjon

last: Verstegen

first: Kexin

last: Zhang

first: Elzo

last: de Wit

first: Wouter

last: de Laat


title: Single-Nucleus RNA Sequencing Reveals HDAC6 Inhibition Reverses Doxorubicin-Induced Cognitive Impairment

city: Houston

first: Rajasekaran

last: Mahalingam

state: TX

address: 6565 MD Anderson Blvd

department: Symptom Research

institute: University of Texas MD Anderson Cancer Center

summary: We used Single nucleus sequencing to understand the transcriptomics changes induced by the HDAC6 inhibitor on Doxorubicin treated mose model

overall_design: Nucleus were were isolated from mice hippocamus forzen tissue and then performed snRNAseq

first: Vena

last: Martinez

first: Blake

last: McAlpin

first: Anand

last: Singh

first: Cobi

middle: J

last: Heijnen

first: Mahalingam

last: Rajasekaran


title: Cross-talk between Cancer-Associated Fibroblasts and Triple Negative Breast Cancer (TNBC) cells in heterotypic clusters

city: Minneapolis

first: Angela

last: Spartz

state: MN

address: 420 Delaware St SE, MMC480

institute: University of Minnesota

summary: Circulating Cancer-Associated Fibroblasts (cCAFs) have been discovered in circulating tumor cell clusters from all stages of disease progression in breast cancer patients. As the most abundant non-cancerous cell type in the tumor microenvironment (TME), CAFs impart many of the tumor promoting functions defined by the hallmarks of cancer such as: proliferation, invasion, migration, metastasis, stemness, immunosuppression, altered cancer cell metabolism, and drug resistance. Human primary CAF cell lines can form co-clusters in vitro with human breast cancer cells when grown in ultra-low attachment conditions. We have previously used these co-clusters to show that they promote metastasis in the mouse tail vein model. In this study, we seek to understand the cross-talk that occurs between CAFs and TNBC  cells when they are present in heterotypic co-clusters compared to TNBC monoclusters or CAF monoclusters. We created samples of mono-clusters and co-clusters grown in 3D conditions for 48 hrs, then disrupted the clusters into a single cell suspension, and subsequently processed them for Single-cell RNA sequencing. Comparisons of breast cancer cells grown as mono-clusters versus co-clusters revealed differentially expressed genes (DEGs) that are up and down regulated in the presence of CAFs. Integration Pathway Analysis and Gene Ontology analysis revealed that CAFs increase expression of several components of the fibrinolysis pathway in breast cancer cells, such as uPA/PLAU and SERPINE1. Upstream regulators identified included TGFbeta. We also looked at DEGs in CAFs when in co-clusters versus mono-clusters and found that when in co-clusters, CAFs become even more CAF-like with the upregulation of genes such as collagens, integrins, and FN1. This study provided us with candidates to study in the process of CAF-mediated breast cancer cell extravasation, such as uPA/PLAU. Pathways identified support our conclusions that circulating CAFs are important players in the metastatic process.

overall_design: CAF23 cells and TNBC cells were cultured together for 48 hrs under non-adherent conditions in ultra low attachment plates to generate 48 in vitro mono-clusters or co-clusters. Clusters were then broken apart into a single cell suspension and processed for Single-cell RNA sequencing.

first: Dorraya

last: El-Ashry

first: Carol

last: Lange


title: Blockade of VCAM1 or VLA4 preserves cerebrovasculature and prevents cognitive decline late after stroke

city: Stanford

first: Kristy

last: Zera

address: 1201 Welch Road

department: Neurology

institute: Stanford University

summary: Infarct-induced neurodegeneration increases dementia risk for at least a decade in humans. It can be modeled in wildtype mice, where a cortical stroke results in chronic lymphocytic infiltration into the infarct and delayed cognitive decline. Vascular cell adhesion molecule 1 (VCAM1) on endothelial cells is increased by stroke and facilitates immune cell diapedesis by binding very late antigen 4 (VLA4) on immune cells. We report here that after stroke, chronic but not acute treatment with an anti-VCAM1 blocking antibody reduces B and T lymphocyte infiltration and prevents chronic cognitive dysfunction in wildtype male and female mice. Preservation of cognitive function was also seen with chronic anti-VLA4 treatment despite anti-VLA4’s lack of effect on lymphocyte infiltration. High-depth single-cell RNA sequencing of the chronic infarct and peri-infarct cortex revealed a pronounced decrease in expression of blood vessel growth and maturation genes in endothelial cells that was reversed by both anti-VLA4 and anti-VCAM1. Plasma proteomics also support a vasculoprotective mechanism of anti-VCAM1. Finally, immunostaining demonstrated that both antibodies improve pericyte coverage of the vasculature and prevent extravascular fibrinogen leakage. Together, our findings indicate that vascular structure and function remain abnormal long after stroke and that the VLA4/VCAM1 axis is a promising treatment target for infarct-induced neurodegeneration as blockade restores cerebrovasculature and prevents cognitive decline.

overall_design: Single cell RNA sequencing of the infarct core and surrounding cortex from 10 month old male mice treated with isotype control, anti-VCAM1 or anti-VLA4 antibody using 10x genomics

first: Karen

last: Bradshaw

first: Li

last: Zhu

first: Oliver

last: Hahn

first: Aulden

last: Foltz

first: Todd

last: Peterson

first: Hanadie

last: Yousef

first: Davis

last: Lee

first: Elizabeth

last: Mayne

first: Nima

last: Aghaeepour

first: Tony

last: Wyss-Coray

first: Marion

last: Buckwalter


title: Identification of targetable epigenetic vulnerabilities for uveal melanoma

city: Miami

first: Stefan

last: Kurtenbach

state: FL

address: 1501 NW 10th Ave

department: Ophthalmology

institute: University of Miami

summary: Uveal melanoma (UM) is the most common adult primary intraocular malignancy, with a strong predilection for hepatic metastasis, occurring in approximately 50% of cases. Metastatic UM remains highly resistant to therapy and is almost invariably fatal. The strongest genetic driver of UM metastasis is loss of function of the tumor suppressor BRCA-associated protein 1 (BAP1), which leads to widespread epigenetic dysregulation. To identify novel therapeutic strategies, we investigated whether targeting the epigenome could reveal new vulnerabilities in UM. We performed high-throughput compound screening using a curated epigenetic inhibitor library and identified BET (bromodomain and extra-terminal domain) inhibition as a particularly promising approach. While previous clinical trials with BET inhibitors for UM treatment have failed clinically, we found substantial heterogeneity in the efficacy of different BET inhibitors in UM. Notably, the BET inhibitor mivebresib (ABBV-075) significantly improved survival rates by 50% in a metastatic UM xenograft mouse model and prevented detectable metastases in the bones, spinal cord, and brain. Transcriptomic analysis revealed a strong overlap between BET inhibition and histone deacetylase (HDAC) inhibition-- an approach currently under clinical evaluation for UM treatment. BET and HDAC inhibitors reversed gene expression signatures associated with high metastatic risk and induced a neuron-like phenotype in UM cells. These findings establish BET inhibition as a potent and previously underappreciated vulnerability for metastatic UM.

overall_design: To investigate the effects on transcription of treatment with epigenetic compounds of interest on uveal melanoma cells, we subjected human uveal melanoma cell line MP38 to 24 hours of high dose treatment with each drug. Bulk RNA sequencing followed by analysis through BioJupies was performed to determine differential gene expression in treated cells.

first: Yenisehirli

last: Gulum

first: Kurtenbach

last: Stefan


title: The Integrator complex is required for optimal lytic lifecycle of Kaposi’s Sarcoma-Associated Herpesvirus [ChIP-seq]

city: Gainesville

first: Conner

middle: Mark

last: Traugot

address: 2033 Mowry Rd, CGRC 265

institute: University of Florida

summary: The Integrator complex (INT) is an essential regulator of RNA biogenesis across evolution. Most current findings describe INT’s function in states of equilibrium, presenting a research gap in INT’s role in dynamic states, such as in infections and cancers. Viruses hijack cellular RNA machinery to transcribe their genes and produce viral progeny, presenting a unique condition to investigate INT-dependent RNA regulation under perturbation. Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic DNA virus that causes two deadly cancers, Kaposi’s sarcoma and primary effusion lymphoma. KSHV undergoes a highly regulated and robust transcription of viral genes upon lytic reactivation, providing a complex and dynamic system to investigate Integrator-mediated viral/host RNA metabolism.  We find that Integrator subunit 11 (INTS11), the enzymatic core of INT, is required for an optimal KSHV lytic lifecycle following reactivation from latency or after primary infection. While INTS11 knockdown’s impact on the human transcriptome remains bi-directional, it almost exclusively represses the KSHV transcriptome throughout the lytic stages. This inhibits viral protein expression, viral genome replication, and virion production. Integrator subunits 9 and 6 are also important for the KSHV lytic lifecycle. RNA-seq analyses revealed dynamic and unique signatures of human transcriptomes during each latent or lytic stage. Mechanistically, ChIP-seq analysis showed that INTS11 is broadly and increasingly recruited to the KSHV genome with unique binding site specificities as the lytic cycle progresses, suggesting that KSHV hijacks INTS11 to facilitate its lytic lifecycle. These findings reveal unexpected and critical roles of the Integrator complex in the lytic phase of KSHV infection.

overall_design: ChIP-seq data showing the binding of host Integrator complex subunit 11 to the KSHV genome upon lytic reactivation

first: Amy

last: Nguen

first: Tianqi

last: Li

first: Kimberly

last: Paulson

first: Mingyi

last: Xie

first: Zhe

last: Ma


title: RRM2-targeted nanocarrier enhances radiofrequency ablation efficacy in hepatocellular carcinoma through ferroptosis amplification and immune remodeling

first: Bufu

last: Tang

address: Shanghai, China

institute: Zhongshan Hospital, Fudan University

summary: Hepatocellular carcinoma (HCC) is associated with high mortality rates despite the widespread application of radiofrequency ablation (RFA), which has limited therapeutic efficacy as a monotherapy. This study investigated ribonucleotide reductase M2 (RRM2) upregulation in post-RFA HCC tissues and developed a targeted nanoco-delivery system (red blood cell membrane/cRGD-modified pH-sensitive liposomes [sS@RBCM/cRGD-phLips]) to increase RFA efficacy through specific RRM2 knockout. RRM2 knockout  synergistically amplified RFA-induced tumor cell death by promoting ferroptosis and immunogenic cell death. Mechanistically, RRM2 knockout upregulated the STAT1–IRF1–acyl-CoA synthetase long-chain family member 4 axis, which potentiated lipid peroxidation and ferroptosis. Furthermore, the nanocarrier system enhanced dendritic cell maturation and cytotoxic T cell infiltration, thereby remodeling the tumor immune microenvironment. In vivo experiments revealed that the combination of RFA- and RRM2-targeted nanoparticles significantly suppressed tumor growth and prolonged survival in HCC-bearing mice with minimal systemic toxicity. Notably, the dual-loaded nanoparticles also enhanced the efficacy of anti-programmed cell death protein 1 therapy, suggesting a promising combinatorial approach for HCC treatment. This study presents a novel therapeutic strategy that integrates RRM2-targeted gene editing with RFA, offering a robust and synergistic approach for improving HCC outcomes.

overall_design: The nanocarrier platform targets RRM2 in tumors and delivers iron oxide. Using a subcutaneous tumor model in C57BL/6J mice, the anti-tumor effects and mechanisms of the RRM2-targeted nanocarrier liver cancer were explored.  Animal species: C57BL/6J mice; The experimental procedures included raising the mice, subcutaneously injecting LLC lung cancer cells, Hepal-6 liver cancer cells,  and delivering drugs to the mice through a nano-carrier platform. After euthanasia, the tumor tissues were dissected.

first: Weiliang

last: Hou

first: Weifeng

last: Hong

first: Songhua

last: Cai

first: Dandan

last: Guo

first: Zhiping

last: Yan

first: Jinyu

last: Zhu

first: Yang

last: Shen

first: Juncheng

last: Wan

first: Xudong

last: Qu

first: Wen

last: Zhang

first: Runkang

last: Zhao

first: Zhao

first: Zhongji

last: Chen

first: Tong

last: Jiang

first: Yaling

last: Lin

first: Wenlong

last: Jia

first: Ling

last: Wang

last: Huang

first: Xuexin