title: Gene expression profile at single cell level from hippocampus of wild type mice and Camk2a-Vps13D KO mice

city: Unionville

first: Haibo

last: Liu

state: CT

address: 164 Plantation St

department: MCCB

institute: UMass Chan

summary: The failure to clear mitochondria, cell death and inflammation have been linked in neurodegenerative disease, but the relationship and role of inflammation in these conditions is not fully understood.To investigate it, we established a model for neurodegeneration caused by mitochondrial impairment by removing Vps13D from the hippocampus.We use single cell RNA sequencing to analyze the gene expression profile of wild type mice and Camk2a-Vps13D KO mice.

overall_design: Hippocampus single cell suspensions from wild type mice and Camk2a-Vps13D KO mice were used to generate scRNA-seq libraries with Chromium Next GEM Single Cell 3' Reagent Kits v3.1.

first: Miao

last: Guangyan

first: Baehrecke

last: Eric

first: Liu

last: Haibo

first: Zhu

last: Lihua (Julie)


title: Recurrent FGFR-alterations are frequent oncogenic drivers and therapeutic targets in pediatric low-grade gliomas

status: Public on May 16 2025

city: Boston

first: April

last: Apfelbaum

state: MA

address: 450 Brookline Ave

department: Pediatric Oncology

country: USA

institute: Dana-farber Cancer Institute

type: Expression profiling by high throughput sequencing

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series

first: Pratiti

last: Bandopadhayay


title: Genomic stratification based on SMAD4 in pancreatic cancer reveals biological implications of aberrant TGFβ signaling and susceptibility to TGFβ inhibition

status: Public on May 15 2025

city: Dallas

first: Rolf

middle: A

last: Brekken

state: TX

address: 6000 Harry Hines Blvd, MC8593

department: Surgery

institute: UT Southwestern

summary: Only 13% of newly diagnosed pancreatic cancer cases are surgically resectable, emphasizing the importance of systemic therapy. Yet, the 5-year overall survival rate for pancreatic cancer remains ~13%, underscoring the urgent need for new treatment strategies. TGFβ is a promising target due to its significant involvement in the desmoplasia, immune suppression, and chemoresistance characteristic of pancreatic cancer. Over 300 clinical trials targeting TGFβ have been conducted in unselected patient cohorts; however, none have gained FDA approval. Nevertheless, TGFβ blockade may hold promise for a subset of cancers with non-functional TGFβ signaling. Greater than 25% of pancreatic cancers carry mutations in SMAD4, a key component of canonical TGFβ signaling. In this study, we investigate the potential for stratifying patients based on SMAD4 mutational status to identify tumors susceptible to TGFβ inhibition. Analysis of SMAD4 expression in human pancreatic tumors reveals that SMAD4 mutation or loss is associated with worse disease-free survival. Intriguingly, we observe heterogeneity in intratumoral SMAD4 expression among human pancreatic cancer samples. To investigate the consequences of SMAD4 mutation, we employed SMAD4-deficient genetically engineered mouse models and orthotopic SMAD4 knockout models, which exhibited reduced survival, increased metastasis, and alterations in the tumor microenvironment compared to SMAD4 wildtype controls, consistent with gene and protein expression changes in the absence of functional SMAD4. Importantly, mice bearing SMAD4-deficient tumors treated with a blocking TGFβ antibody exhibited reduced tumor weight and improved survival. These findings suggest that targeting TGFβ signaling in TGFβ-deficient tumors has potential utility in pancreatic cancer.

overall_design: RNAseq profiling BMFA3V1-EV (empty vector controrol) and - Smad4KO and  6620c1-EV (empty vector control) and - Smad4KO cells, untreated or treated with TGFb (30ng/ml, 48h).

first: Gilbert

middle: Z

last: Murimwa

first: Natalie

middle: E

last: Williams

first: Dina

last: Alzhanova

first: Amir

last: Mohammadi

first: Jill

middle: M

last: Westcott

first: Francisca

last: Beato

first: Ruifan

last: Dai

first: Luis

last: Nivelo

first: Francesca

last: Rossi

first: Henry

middle: K

last: Fleming

first: Alexandra

middle: F

last: Tassielli

first: Zeynep

last: Yazgan

first: Jason

last: Toombs

middle: B

first: Aatur

middle: D

last: Singhi

first: Cecilia

middle: G

last: Ethun

first: Huocong

last: Huang


title: Transcriptomic Profiling of TNFα-Stimulated Human Umbilical Vein Endothelial Cells (HUVECs) With and Without Isoginkgetin (ISOGK) Pretreatment.

city: Hefei City

first: ZHIDAN

last: ZHANG

state: Anhui Province

address: No. 96 Jinzhai Road

country: China

institute: University of Science and Technology of China

summary: We demonstrate that ISOGK attenuates endothelial inflammation through mechanistically distinct suppression of NF-κB p65 phosphorylation and nuclear translocation, highlighting its potential as a therapeutic agent for atherosclerosis intervention. This anti-inflammatory effect was associated with significant modulation of inflammatory pathway activation in vascular endothelial cells.

overall_design: HUVECs were pretreated with 7.5 μM ISOGK for 12 hours prior to 6-hour stimulation with 10 ng/mL TNFα. Comparative transcriptomic analysis was subsequently performed to characterize ISOGK-mediated modulation of inflammatory responses.

first: Suowen

last: Xu

first: Zhidan

last: Zhang


title: Aged induced periosteal changes during early fracture healing

city: Farmington

first: Justin

middle: S

last: King

state: Connecticut

address: 263 Farmington Ave

institute: UConn Health

summary: The periostieum is a fiberous network on the outside of the bones crucial to fracture healing. Here we present our scRNA-seq data from intact and fractured periosteal cells, collected three days after injury, from young adult and aged mice.

overall_design: Femur periosteal cells of C57/BL6 mice were isolated by Fluorescence-activated cell sorting (FACS) according by Ter119-CD45- or Ter119-CD45+ populations and analyzed using scRNA-seq.


title: Transcriptional response to the SARS-CoV-2 Delta variant in patients with severe COVID-19

city: Moscow

first: Ivan

middle: Nikolaevitch

last: Vlasov

address: Akademika Kurchatova square, 2

country: Russia

institute: National Research Center «Kurchatov Institute»

summary: For a more precise understanding of the course of the pathological process in patients with severe COVID-19, it is necessary to continue the search for factors that affect the course of the pathological process and the possibility of a favorable outcome in critically ill patients. Comparative analysis of the transcriptome of peripheral blood mononuclear cell (PBMCs) in patients with a severe clinical course of COVID-19 caused by the SARS-CoV2 Delta strain revealed a number of differentially expressed genes that distinguish patients with different clinical outcomes (survivors vs. nonsurvivors) in the period of 30 days after admission to the hospital. resuscitation. Most of them are associated with the "negative regulation of viral process" and "negative regulation of immune response" clusters. Moreover, in surviving patients, there is increased expression of the key genes C1QB, C1QA, ISG15, SERPING1, VSIG4, KLRD1, TRPM4, and HFE incorporated in these clusters. Among these key genes, the ISG15 gene, which links several clusters of GO enrichments and encodes an interferon-induced ubiquitin-like protein, deserves special attention. An increase in the level of expression of the ISG15 protein may play a role in response to the expression of the viral protease PLpro, but the exact role of this protein in the prevention of negative disease outcomes is not yet clear.

overall_design: Examination of transcriptiomic profiles of the blood, derived from surviving and deceased COVID-19 patients, infected with Delta variant of SARS-CoV-2.

first: Tatiana

last: Usenko

last: Panteleeva

first: Mikhael

last: Nikolaev

first: Artem

last: Izumchenko

first: Valeriia

last: Panafidina

first: Elena

last: Gavrilova

first: Irina

last: Shlyk

first: Valentina

last: Miroshnikova

first: Maria

last: Shadrina

first: Yurii

last: Polushin

first: Sofya

last: Pchelina

first: Petr

last: Slominsky


title: Impact of BCL2 inhibitor Venetoclax  on  LNCaP cells

city: New York

first: Nabila

last: Zaman

state: New York

address: 1425 Madison Ave, 15-52

institute: Mount Sinai

summary: In analyzing transcriptomic data from a clinical trial of neoadjuvant-intensive Androgen Deprivation Therapy, we observed increased mRNA expression of the hallmark antiapoptotic gene BCL2 in the prostate tumors of treated patients versus those of untreated patients.  We showed that BCL2 overexpressed LNCaP cells exhibited resistance to enzalutamide, indicating that BCL2-overexpression leads to castration resistance and cellular plasticity.We treted the LNCaP cells with Bcl2 inhibitor Venetoclax in under castration of in presence of Androgen for 24 hr and observed that androgen supressed Venetoclax function

overall_design: To investigate the function of BCL2 inhibtor Venetoclax , tretaed LNCaP cells to Venetoclax in absence or presence of  R1881 for 24 hr and perfermed RNA sequencing

first: Subhiksha

last: Nandakumar

first: Goutam

last: Chakraborty


title: Impact of androgen stimulation on BCL2 Overexpressed LNCaP cells

summary: In analyzing transcriptomic data from a clinical trial of neoadjuvant-intensive Androgen Deprivation Therapy, we observed increased mRNA expression of the hallmark antiapoptotic gene BCL2 in the prostate tumors of treated patients versus those of untreated patients.  We showed that BCL2 overexpressed LNCaP cells exhibited resistance to enzalutamide, indicating that BCL2-overexpression leads to castration resistance and cellular plasticity.We performed RNA sequencing on BCL2 overexpressed LNCaP cells tretaed with R1881 to determine BCL2 regulated AR signaling and overed that BCL2 overexpression may alter AR-pathway.

overall_design: To investigate the function of BCL2 overexpression, we stably overexpressed humna BCL2 in LNCaP cells. We grow the isogenic pairs of cells to R1881 and perfermed RNA sequencing


title: Impact of BCL2 Overexpression in castration resistance prostate cancer progression I

summary: In analyzing transcriptomic data from a clinical trial of neoadjuvant-intensive Androgen Deprivation Therapy, we observed increased mRNA expression of the hallmark antiapoptotic gene BCL2 in the prostate tumors of treated patients versus those of untreated patients.  We showed that BCL2 overexpressed LNCaP cells exhibited resistance to prolonged androgen deprivation therapy, indicating that BCL2-overexpression leads to castration resistance and cellular plasticity.Our study indicating that BCL2 overexpression may act as a major driver of early castration resistance in prostate cancer cells.

overall_design: To investigate the function of BCL2, we stably overexpressed humna BCL2 in prostate cancer cells. We grow the isogenic pairs of cells to androgen deprivation for a prolonged time (28 days) and perfermed RNA sequencing


title: Effect of hypoxia on HIF-1α binding genes in MDA231-BrM2 breast cancer brain-selective metastatic cells with ChIP-Seq.

city: Baltimore

first: YONGKANG

last: YANG

state: Maryland

address: Room 673, MRB, 725 North Broadway

department: ICE

institute: Johns Hopkins University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Brain metastasis is a major cause of breast cancer mortality, but the molecular basis and pathological mechanisms are poorly understood. Here, we determined that integrin β3 (ITGB3) expression mediated by hypoxia-inducible factor 1 (HIF-1) plays a critical role in brain metastasis of breast cancer. Hypoxia induces HIF-1-dependent expression of ITGb3, which is required for breast cancer cell migration and invasion. Knockdown of HIF-1a or ITGB3 expression impairs the colonization of breast cancer cells to brain after injection into the cardiac left ventricle. Mechanistically, ITGB3 protein expressed by breast cancer cells was incorporated into extracellular vesicles (EVs). The ITGb3+ EVs associated with brain endothelial cells, activated vascular endothelial growth factor receptor 2 signaling, and increased endothelial permeability to facilitate metastatic colonization of the brain.

overall_design: ChIP-seq for HIF-1α in MDA231-BrM2 cells. Comparative HIF-1α binding gene profiling analysis of ChIP-seq data for MDA231-BrM2 cells that were exposed in 20% or 1% oxygen condition for 16 hours.

first: Yongkang

last: Yang

first: Gregg

middle: L

last: Semenza


title: mRNA-seq of human adipose tissue-derived mesenchymal stem/stromal cells (MSCs)

city: Tokyo

first: Daisuke

last: Hisamatsu

address: 2-1-1 Hongo, Bunkyo-ku

country: Japan

institute: Juntendo University Graduate School of Medicine

summary: We isolated MSCs using fluorescence-activated cell sorting with CD73 molecule as a marker (termed isolated MSCs). We also established conventional heterogeneous adhered MSCs derived from the same specimens (termed adhered MSCs). We examine the interindividual variability between isolated and adhered MSCs based on gene expression profiles.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for isolated and adhered MSCs derived from the same samples.

first: Chihiro

last: Akazawa


title: Effect of depletion of hypoxia-inducible factor (HIFs) on gene expression in MDA231-BrM2 breast cancer brain-selective metastatic cells with RNA-Seq.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MDA231-BrM2 subclone of NTC and HIFs knockdown that were exposed in 20% or 1% oxygen condition for 24 hours.


title: Overcoming resistance to immunotherapy by targeting CD38 in human tumor explants  II

status: Public on May 14 2025

first: Or-Yam

middle: GENERAL

last: Revach

address: 55 fruit street

institute: MGH

summary: CD38, an ecto-enzyme involved in NAD+ catabolism, is highly expressed in exhausted CD8+ T cells and has emerged as an attractive target to improve response to immune checkpoint blockade (ICB) by blunting T cell exhaustion. However, the precise role(s) and regulation of CD38 in exhausted T cells and the efficacy of CD38-directed therapeutic strategies in human cancer remain incompletely defined. Here, we show that CD38+CD8+ T cells are induced by chronic TCR activation and type I interferon stimulation and confirm their association with ICB resistance in human melanoma. Disrupting CD38 restores cellular NAD+ pools and improves T cell bioenergetics and effector functions. Targeting CD38 restores ICB sensitivity in a cohort of patient-derived organotypic tumor spheroids from explanted melanoma specimens. These results support further preclinical and clinical evaluation of CD38-directed therapies in melanoma and underscore the importance of NAD+ as a vital metabolite to enhance those therapies.

overall_design:
scRNAseq of CD8+ TILs from human melanoma cohort treated with ICB.

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

first: Genevieve

last: Boland

first: Manolis

last: Kellis


title: Reactivation of CTLA4-expressing T cells accelerates resolution of lung fibrosis in a humanized mouse model

city: New Orleans

first: Victor

middle: J

last: Thannickal

state: LA

address: 333 South Liberty Street

department: Medicine

institute: Tulane University

summary: We performed single-cell sequencing to characterize the cellular landscape in mice treated with IgG1 or ipilimumab.

overall_design: Humanized CTLA4 mice were obtained from genOway and housed in the Tulane University Vivarium. Twelve-week-old male mice were used for all experiments. Pulmonary fibrosis was induced by oropharyngeal administration of bleomycin (1.25 U/kg body weight) delivered in two doses, 2 weeks apart, under isoflurane/oxygen anesthesia. On day 21, mice in the control group received intraperitoneal injections of IgG1 isotype control antibody ( Bio X Cell), while mice in the treatment group received ipilimumab (Bio X Cell) at 5 mg/kg body weight, administered twice weekly for 4.5 weeks. At study completion, mice were euthanized; the right lung was harvested for single-cell RNA sequencing.

first: Santosh

last: Yadav


title: Controlling mitochondrial membrane architecture via MIC60 determines viral replication to promote anti-viral immunity

city: Düsseldorf

first: Lang

middle: A.

last: Philipp

state: NRW

address: Universitätsstrasse 1

department: Department of Molecular Medicine II

country: Germany

institute: University Hospital Duesseldorf

summary: Virus-infected cells often exhibit dramatic cellular changes accompanied by altered mitochondrial function. The contribution of factors shaping the inner mitochondrial membrane (IMM) and cristae architecture on viral replication is insufficiently understood. Single cell transcriptomics applying vesicular stomatitis virus (VSV) infection suggests involvement of factors determining IMM architecture following infection. Consistently, inhibition of the F1Fo ATP synthase reduces viral replication which is associated with oligomerization of the complex and altered IMM structure. Moreover, deletion of mitochondrial contact site and cristae organizing system (MICOS) complex by targeting MIC60 results in reduced viral replication. Generation of Mic60inv/inv CD11c-Cre+ mice uncovers reduced crista junctions and viral replication in bone marrow-derived dendritic cells. Consequently, reduced viral replication in CD11c-expressing cells limits prolonged immune activation. Altogether, by linking the F1Fo ATP synthase and the MICOS complex to viral replication and immune activation, we describe links between the mitochondrial structure-metabolism and the immune response against viral infection.

overall_design:
To identify factors driving viral infection and propagation we analysed transcripts of partly infected cells at a single cell level using the vesicular stomatitis virus (VSV) model system.
Please note that the cells were treated in triplicate and pooled as one sample after labeling by cell multiplexing oligo (CMO). Specifically:
- 550-1 was labeled with CMO 307,308,309
- 550-3 was labeled with CMO 304,305,306


title: Population RNA-seq from Th17 cells differentiated in vitro under pathogenic (Th17p) and non-pathogenic (Th17n) conditions with DHEA or EGCG

city: Berkeley

first: Allon

last: Wagner

state: CA

address: 378 Stanley Hall

institute: UC Berkeley

summary: We investigated the effect of glycolytic inhibitors on Th17 differentiation

overall_design: Th17 cells were differentiated in vitro under pathogenic (Th17p; IL1b+IL6+IL23) and non-pathogenic (Th17n; TGFb+IL6) conditions with EGCG (20uM), DHEA (50uM) or their respective solvent control. Five biological replicates (mice) per condition. Cells were pre-labeled with division dye to allow sorting cells that underwent one cell division (Div.1) from the total cell population (Total).

first: Chao

last: Wang

first: Johannes

last: Fessler

first: Nir

last: Yosef

first: Vijay

last: Kuchroo


title: Genetic and Phenotypic correlates of clinical outcomes with Venetoclax in Acute Myeloid Leukemia: The GEN-PHEN-VEN study

city: Portland

first: Theodore

middle: Paul

last: Braun

state: OR

address: 3181 SW Sam Jackson Park Road

department: Knight Cancer Institute

institute: OHSU

summary: Resistance to venetoclax-based therapy in acute myeloid leukemia (AML) includes genetic (i.e., mutations in N/KRAS, FLT3-ITD, TP53) and phenotypic (i.e., monocytic differentiation) features. Whether monocytic differentiation contributes to clinical venetoclax resistance secondary to a genetic bias remains unknown. This multimodal, multicenter, international analysis inclusive of 678 patients comprehensively characterized the prognostic role of monocytic differentiation in AML patients treated with hypomethylating agents combined with venetoclax. AML genetics and monocytic differentiation (HR: 1.89, 95% CI: 1.35-2.66, p < 0.001) in NPM1 wild-type cases correlated with an increased risk of death. Clustering of centralized quantitative multiparameter flow cytometry data, evaluation of RNA sequencing-derived AML maturation stage, and single-cell proteogenomics linked driver mutations with AML phenotype and anti-apoptotic gene expression. This comprehensive analysis of AML genetics, phenotype, and anti-apoptotic protein expression highlights the complementary role these factors impart following venetoclax-based therapy.

overall_design: Multi-modal study incorporating clinical data, RNAseq from the Beat AML project, and additional sequencing using Mission bio DNA+protein seq from diagnostic specimens and specimens post 1 cycle of HMA+VEN treatment for AML.

first: Curtis

last: Lachowiez

first: Anupriya

last: Agrawal


title: Overcoming resistance to immunotherapy by targeting CD38 in human tumor explants

overall_design:
scRNAseq of CD8+ TILs from human melanoma tumors processed for PDOTS profiling and responded (R) or did not respond (NR) to PD-1+CD38 blockade combination therapy ex vivo

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No raw files data due to patient-privacy concerns
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first: Baolin

last: Liu


title: Clec12a is required for the pathogenesis of NUP98::NSD1 AML

city: Halle

first: Razif

last: Gabdoulline

state: Sachsen-Anhalt

address: Ernst-Grube-Straße 40

department: Innere Medizin IV Haematologie und Onkologie

institute: Universitätsklinikum Halle

summary: NUP98-NSD1 is one of the most recurring nucleoporin 98 (NUP98) fusions in acute myeloid leukemia (AML). NUP98-NSD1 AML is associated with adverse outcomes and poor response to conventional treatments. However, limited studies have been done to identify new potential targets to develop better treatment approaches. The C-type lectin domain family 12, member A (CLEC12A) is a cell surface receptor that is differentially expressed in leukemic stem cells (LSCs) compared to healthy hematopoietic stem cells (HSCs). We demonstrated a strong overexpression of CLEC12A in both NUP98-NSD1 patients and NUP98-NSD1 transformed murine cells. To understand the role of Clec12a in NUP98-NSD1 AML, we depleted Clec12a expression in NUP98-NSD1+NRASG12D immortalized cells using 3 different sgRNAs targeting 3 different exons. We observed an efficient gene editing in all target sites. NUP98-NSD1+NRASG12D/Clec12a knockout cells showed higher apoptosis and lower colony numbers in vitro compared to NUP98-NSD1+NRASG12D/Clec12a wildtype cells. Importantly, the deletion of Clec12a significantly reduced the leukemic engraftment and prolonged the survival of the NUP98-NSD1+NRASG12D murine model. Our data suggest to further explore CLEC12A as a potential target for the treatment of NUP98-NSD1 AML.

overall_design: To deplete the expression of Clec12a from NUP98-NSD1+ NRASG12D immortalized murine bone marrow cells, we designed 3 distinct sgRNAs against Clec12a. We cloned these sgRNAs into the Cas9-expressing lentiviral vector L40C-CRISPR.EFS.dTomato, and the dTomato reporter was used to select sgRNA transduced cells. A sgRNA against the lacz gene was used as transduction control. For gene expression profiling, we used the Clec12a T44 sgRNA and the lacZ control. Following transduction, single-cell sorting was performed in triplicate. Once the cells expanded, total RNA was isolated and sent for sequencing.

first: Sagarajit

last: Mohanty

first: Fiorella

last: Charles Cano

first: Michael

last: Heuser


title: Mgat4b mediated selective N-glycosyl modification regulates melanocyte development and melanoma progression [bulk RNA-seq]

city: Delhi

first: Vivek

middle: T

last: Natarajan

state: Delhi

address: Mathura Road

country: India

institute: CSIR-IGIB

summary: Dysregulated melanocyte state transitions are a pivotal driver of melanoma development, highlighting the need to identify key regulators of these processes. Understanding these factors is key to know how normal melanocyte functions and shift towards initiation of melanoma. Our study identifies Mgat4b, a glycosyl transferase involved in selective N-glycan branching enriched in pigment progenitors, as a key regulator of directional melanocyte migration and establishment of Melanocyte stem cell (McSC) pool during early development in zebrafish and mammalian melanocytes. Single cell RNA sequencing analysis in zebrafish upon targeted disruption of Mgat4b reveals that a subset of melanocytes marked by aberrant galectin expression are impaired in migration and are lost. Lectin binding proteomic analysis reveals the glycosylation of key melanocyte proteins Gpnmb, Kit, and Tyrp1 to be under the control of Mgat4b. Additionally, mislocalization of Gamma catenin (Jup) explains the observed defects in cell adhesion and migration to be regulated by mgat4b but not its isozyme mgat4a. Our meta-analysis further revealed that melanoma patients with both the BrafV600E mutation and elevated Mgat4b levels have significantly worse survival outcomes compared to those with only the BrafV600E mutation. By leveraging the MAZERATI platform to model BrafV600E driver mutation in vivo, we show that Mgat4b mutant cells fail to aggregate and initiate tumors. Our study underscores the importance of selective N-glycan branching in both melanocyte development and melanoma initiation, suggesting a Mitf controlled Mgat4b as a promising therapeutic target for melanoma treatment.

overall_design: To investigate the mechanisms that inhibit mutant cells from initiating melanoma in the absence of mgat4b, we utilized mature melanophores and melanoma cells from the skin of five zebrafish, including both MAZERATI wild-type and  MAZERATI zebrafish carrying mgat4b mutations. We then performed gene expression profiling analysis using data obtained from RNA-seq of melanophores and melanoma cells from both the zebrafish (wild-type and m4b mut). Comparative gene expression analysis was performed for wild-type melanoma and melanophores, m4b mut melanoma and melanophores, wild-type and m4b mut melanoma.

first: Babita

last: Sharma

first: Keerthic

last: Aswin

first: Tanya

last: Jain

first: Ayesha

last: Nasreen

first: Ayush

last: Aggarwal

first: Yogaspoorthi

last: Subramaniam

first: Jeyashri

last: Rengaraju

first: Srashti

last: Jyoti Agrawal

first: Mayank

last: Bhatt

first: Bhaskar

last: Paul

first: Koushika

last: Chandrasekaran

first: Aanchal

first: Jyoti

last: Soni

first: Rajat

last: Ujjainiya

first: Md Quasid

last: Akhter

first: Shantanu Sen

last: Gupta

first: Rajesh

last: Pandey

first: Shruthy

last: Suresh Aggarwal

first: Srinivasa-Gopalan

last: Sampathkumar

last: T Natarajan


title: Gene expression profile in meningioma patients at the single cell level

city: Seoul

first: Ji Yoon

last: Lee

address: 161, Jeongneung-ro, Seongbuk-gu

country: South Korea

institute: Korea university

summary: Using snRNA seq to know the characteristics and microenvironment of high-grade recurrent meningioma and find prognostic factors.

overall_design: Analyzing what differences exist between primary and recurrent samples using 6 primary samples and 8 recurrent samples obtained from 7 meningioma patients.


title: Role of the SAF-A SAP domain in X inactivation, transcription, splicing, and cell proliferation [CutandRun]

first: Michael

last: Blower

address: 72 E. Concord St. K123C

department: Biochemistry and Cell Biology

institute: Boston University

summary: SAF-A is conserved throughout vertebrates and has emerged as an important factor regulating a multitude of nuclear functions, including lncRNA localization, gene expression, and splicing. SAF-A has several functional domains, including an N-terminal SAP domain that binds directly to DNA. Phosphorylation of SAP domain serines S14 and S26 are important for SAF-A localization and function during mitosis, however whether these serines are involved in interphase functions of SAF-A is not known. In this study we tested for the role of the SAP domain, and SAP domain serines S14 and S26 in X chromosome inactivation, protein dynamics, gene expression, splicing, and cell proliferation. Here we show that the SAP domain serines S14 and S26 are required to maintain XIST RNA localization and polycomb-dependent histone modifications on the inactive X chromosome in female cells. In addition, we present evidence that an Xi localization signal resides in the SAP domain. We found that that the SAP domain is not required to maintain gene expression and plays only a minor role in mRNA splicing. In contrast, the SAF-A SAP domain, in particular serines S14 and S26, are required for normal protein dynamics, and to maintain normal cell proliferation. We propose a model whereby dynamic phosphorylation of SAF-A serines S14 and S26 mediates rapid turnover of SAF-A interactions with DNA during interphase.

overall_design:
To understand how SAF-A contributes to gene expression, mRNA splicing, and X chromosome inactivation we established a Auxin Inducible Degron cell line for SAF-A in RPE-1 cells. We then rescued SAF-A depletion using inducible point mutants on the SAP domain.
We performed Cut and Run using antibodies for H3K4Me3 and H3K27Ac
We analyzed allele-specific Cut and Run binding sites using PAC


title: Hepatitis B virus promotes hepatocellular carcinoma (liver cancer) by modulating the immune response to environmental carcinogens

first: Shadmehr

last: Demehri

address: 149 13th Street

institute: Cutaneous Biology Research Center, Harvard Medical School

summary: Hepatitis B virus (HBV) infection is a globally significant threaten to global health, with the potential to progress to hepatitis and hepatocellular carcinoma (HCC). Despite the availability of a vaccine, a population with non-responders, emphasizing the need for continued research into HBV-mediated immune responses. Interleukin-33 (IL-33) has emerged as a pivotal player in chronic inflammation and cancer, yet its role in specific viral contexts remains elusive. Here, we demonstrate the immune mechanisms underlying HBV infection and its contribution to HCC development. HBV with liver carcinogens induced IL-33 expression. Utilizing IL-33 and ST2 knockout mice, we demonstrate impaired HBV- mediated tumor progression, highlighting the critical involvement of IL-33 axis. Furthermore, we identify ST2 positive regulatory T cells (Treg) is a major effector cells with IL-33 in HBV-infected mice. ST2-deficient Tregs triggers immune cell infiltration, accompanied by reduced expression of immunosuppressive cytokines such as IL-10. Blocking this axis with STATIN, IL-33 inhibitor, shows promise therapeutic drug in chronic hepatitis and HCC in human subjects. In conclusion, our study reveals that IL-33/Treg axis as a critical mediator in hepatitis and its cancer development.

overall_design: Whole liver RNA sequencing was performed on HBV-DEN and Sham-DEN mice at this time point. HBV-DEN group showed positive upregulation of hepatitis related genes compared to Sham-DEN mice by Gene Set Enrichment Analysis

first: JongHo

last: Park

first: Mei

last: Huang


title: Functional Targeting of ILC2s and ILC3s reveals selective roles in intestinal fibrosis and homeostasis.

city: Vancouver

first: Lesley

last: Hill

state: BC

address: 2222 Health Sciences Mall

country: Canada

institute: University of British Columbia

summary: Innate lymphoid cells (ILCs) are long-lived tissue-resident analogues to T helper cell subsets that lack antigen-specific receptors. Understanding the roles of specific ILC subsets in chronic inflammation and fibrosis has been hampered by a lack of adequate tools for their selective targeting. Here, we used two Cre-deleter strains, Il17rb-CreERT2-eGFP and Rorc-Cre, to selectively delete RORa, a master transcriptional regulator, in ILC2s and ILC3/Th17 cells, respectively. Deletion of RORa in ILC2s led to a significant loss of gastrointestinal ILC2s, a concomitant increase in ILC3s, elevated Th17-type responses, and heightened susceptibility to Crohn’s-like fibrosis in a Salmonella infection model. In contrast, RORa deletion in ILC3/Th17 cells reduced IL-17 production, protecting against fibrosis. We further confirmed the role of IL-17 and ILC3 in fibrotic responses using isolithocholic acid (isoLCA), a microbially-derived secondary bile acid and RORγt inverse agonist. In RORγt reporter and Th17-deficient Rag1−/− mice, isoLCA reduced IL-17 production by ILC3s. In the context of intestinal fibrosis, we show that isoLCA attenuates collagen deposition and fibrotic pathology by dampening RORγt-dependent IL-17 production by ILC3s. These findings reveal a novel interplay between ILC2s and ILC3s in gut homeostasis and demonstrate the therapeutic potential of targeting RORγt in ILC3s as a strategy for preventing fibrosis.

overall_design: RNA-seq profiling of primary intestine fibroblasts treated with IL-17A (20 ng/mL or 200 ng/mL) for 24 hours, or untreated control cells.

first: Ahmed

last: Kabil

first: Natalia

last: Nayyar

first: Chengxi

last: Xu

first: Julyanne

last: Brassard

middle: A

first: Samuel

last: Shin

first: Sameeksha

last: Chopra

first: Bernard

last: Lo

first: Yicong

last: Li

first: Mya

last: Bal

last: Underhill

middle: R

last: Hughes

first: Kelly

last: McNagny


title: Role of the SAF-A SAP domain in X inactivation, transcription, splicing, and cell proliferation [RNA-seq]

last: Blower

overall_design:
To understand how SAF-A contributes to gene expression, mRNA splicing, and X chromosome inactivation we established a Auxin Inducible Degron cell line for SAF-A in RPE-1 cells. We then rescued SAF-A depletion using inducible point mutants on the SAP domain.
We then performed total RNA-seq from WT and mutant cell lines at various time points after SAF-A depletion or allele replacement.
We analyzed bulk differential gene expression, mRNA splicing, and allele-specific expression changes.


title: Role of the SAF-A SAP domain in X inactivation, transcription, splicing, and cell proliferation [ATAC-seq]

overall_design:
To understand how SAF-A contributes to gene expression, mRNA splicing, and X chromosome inactivation we established a Auxin Inducible Degron cell line for SAF-A in RPE-1 cells. We then rescued SAF-A depletion using inducible point mutants on the SAP domain.
We then performed ATAC-seq following SAF-A depleiton.
We analyzed allele-sepcific ATAC-seq reads using PAC.


title: Mgat4b mediated selective N-glycosyl modification regulates melanocyte development and melanoma progression [scRNA-seq]

first: Vivek

last: Natarajan

overall_design: To understand how selective N-glycosylation modification performed by mgat4b promote melanocyte development, we performed single-cell RNA sequencing of mitfa+ve melanophores sorted from the 36hpf staged zebrafish.

first: Babita

last: Sharma

first: Keerthic

last: Aswin

first: Tanya

last: Jain

first: Ayesha

last: Nasreen

first: Ayush

last: Aggarwal

first: Yogaspoorthi

last: Subramaniam

first: Jeyashri

last: Rengaraju

first: Srashti

last: Jyoti Agrawal

first: Mayank

last: Bhatt

first: Bhaskar

last: Paul

first: Koushika

last: Chandrasekaran

first: Aanchal

last: Yadav

first: Jyoti

last: Soni

first: Rajat

last: Ujjainiya

first: Md Quasid

last: Akhter

first: Shantanu Sen

last: Gupta

first: Rajesh

last: Pandey

first: Shruthy

last: Suresh Aggarwal

first: Srinivasa-Gopalan

last: Sampathkumar

last: T Natarajan


title: Role of the SAF-A SAP domain in X inactivation, transcription, splicing, and cell proliferation [DNA-seq]

first: Michael

last: Blower

type: Genome variation profiling by high throughput sequencing

overall_design: We sequenced the genome of RPE-1 cells grown in our lab to verify published SNPs.


title: Single cell RNA-sequencing analysis of chronic graft-versus-host disease (GVHD) skin lesions

city: Durham

first: Jennifer

middle: Yunyan

last: Zhang

state: NC

address: 3 Genome Ct, rm4130

department: Dermatology

institute: Duke University

summary: The goal of the study is to understand the molecular mechanisms responsible for cutaneous GVHD.

overall_design: Skin punch biopsies were collected from adult hematopoietic stem cell transplant patients suffering from chronic GVHD in accordance to an IRB protocol approved by Duke University and with patient consent. Surgical abdominoplasty skin tissues were used for control. The epidermis was separated from the dermis via dispase digestion. Single cell suspensions of the epidermis and the dermis were loaded onto the 10x genomics system for bar coding and cDNA library construction followed by RNA-sequencing.

first: Rambi

last: Cardones

first: Yingai

last: Jin

first: Vaibhav

last: Jain

first: Amy

last: Petty

first: Emily

last: Hocke

first: Simone

last: Gregory

middle: Y


title: Identification of transcription factors dictating blood cell development using a bidirectional transcription network-based computational framework [CAGEseq_MLLAF9-AML 2]

status: Public on May 13 2025

city: Nijmegen

first: Joost

last: Martens

state: Nederland

address: Geert Grooteplein 28

department: RIMLS

country: Netherlands

institute: Radboud University

summary: Genome-wide transcription factor binding profiles provide valuable insights into hematopoietic development and malignancies. Today, advanced computational methods exploit cis-regulatory information to predict complex gene regulatory networks controlled by transcription factors. However, these prediction methods still require large amounts of reference data or experimental expertise. Here, we present a low-requirement network-based computational framework that exploits bidirectional transcription marked regulatory elements to identify important transcription factors driving hematopoietic decision making. Using CAGE-seq we predicted TF binding and confirmed experimentally validated TF important in cell conversion strategies by exploiting bidirectional regions. Next, we applied our framework to predict driving transcription factors in induced normal erythropoiesis and early myelopoiesis, as well as in acute myeloid leukemia associated MLL-AF9-driven immortalisation. Our approach allowed the identification of experimentally validated as well as thus far unexplored transcription factors in these processes.

overall_design: Comparative CAGE transcription start sites (CTSS) expression profiling analysis of CAGE-seq data for primary CD14+ monocytes (FANTOM5 database) and MLL-AF9 AML.

first: Branco

last: Heuts

first: Saioa

last: Apalategi

first: Bert

last: van der Reijden


title: Single-cell RNA-seq from Th17 cells differentiated in vitro under pathogenic (Th17p) and non-pathogenic (Th17n) conditions with high (25mM) or low (1mM) glucose media concentration

first: Allon

last: Wagner

summary: We investigated the effect of glucose media availability on Th17 differentiation

overall_design: Th17 cells were differentiated in vitro under pathogenic (Th17p) and non-pathogenic (Th17n) conditions with high (25mM) or low (1mM) glucose media concentrations. Two biological replicates (mice) per condition.

first: Chao

last: Wang

first: Johannes

last: Fessler

first: Nir

last: Yosef

first: Vijay

middle: K

last: Kuchroo


title: Differentially expressed mRNA in biological premature ovarian insufficient (bPOI)

city: Jinan

first: Nianyu

last: Li

state: ShanDong

address: 44 wenhua xi road

institute: Shandong University

summary: We have completed the mRNA expression profiling of human granulosa cells to reveals the differentially expressed mRNAs involved in POI.

overall_design: RNA sequencing in ovarian granulosa cells from patients with bPOI and normal people.

first: Xue

last: Jiao

first: Hanbing

last: Zhu


title: FGF21 reverses MASH through coordinated actions on the CNS and liver

city: Oklahoma City

first: Matthew

last: Potthoff

state: Oklahoma

address: 1100 N Lindsay Ave

institute: University of Oklahoma health sciences center

summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, metabolic dysfunction-associated steatohepatitis (MASH), represent a growing public health burden with limited therapeutic options. Recent studies have revealed that fibroblast growth factor 21 (FGF21)-based analogs can significantly improve MASH, but the mechanisms for this effect are not well understood. Here, we demonstrate that the beneficial metabolic effects of FGF21 to reverse MASH are mediated through distinct mechanisms to independently lower hepatic triglyceride and cholesterol levels. Specifically, FGF21 signaling directly to glutamatergic neurons in the central nervous system (CNS) stimulates hepatic triglyceride reduction and reversal of fibrosis, whereas FGF21 signaling directly to hepatocytes is necessary and sufficient to reduce hepatic cholesterol levels in mice. Mechanistically, we show that FGF21 acts in the CNS to increase sympathetic nerve activity to the liver which suppresses hepatic de novo lipogenesis. These results provide critical insights into a promising pharmacological target to treat MASH.

overall_design: RNAseq analysis of whole liver from chow or diet-induced MASH C57BL6 mice after 4 weeks of treatment with FGF21 (1 mg/kg/day) or saline vehicle.

first: Jesse

last: Rose


title: Gene expression at single cell level of stromal cells from the distal colon of normal sites of colorectal cancer and inflamed sites of ulcerative colitis.

city: Suita

first: Daisuke

last: Okuzaki

state: Osaka

address: Main Building, 3-1 Yamadaoka,

department: Immunology Frontier Research Center

institute: Osaka University

summary: Glial cells are considered as anti-inflammatory population in the lamina propria. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of stromal cells in the lamina propria of colon.

overall_design: Live CD90+CD45-CD31-EpCAM- stromal cells from human lamina propria mononuclear cells (LPMCs) of colorectal cancer and ulcerative colitis (UC) were isolated by Fluorescence activated cell sorting (FACS) and analysed using scRNA-seq.

first: Hazuki Miyazaki

last: Yuki Ito

first: Takayuki Ogino

last: Hiroyuki Itoi

first: Bo-Li

last: Yuki sekido

first: Ryota Mori

last: Terukazu Yoshihara

first: Liu Yuchen

last: Daisuke Okuzaki

first: Mitsunobu Takeda

last: Tsuyoshi Hata

first: Atsushi Hamabe

last: Norikatsu Miyoshi

first: Mamoru Uemura

last: Yuichiro Doki

first: Hidetoshi Eguchi

last: Kiyoshi Takeda

first: Hisako

last: Kayama


title: Single cell RNA-sequencing analysis of acute graft-versus-host disease (GVHD) skin lesions

first: Jennifer

last: Zhang

overall_design: Skin punch biopsies were collected from adult hematopoietic stem cell transplant patients suffering from acute GVHD in accordance to an IRB protocol approved by Duke University and with patient consent. The epidermis was isolated from the dermis via overnight incubation with 1X dispase at 4 °C. Single cell suspensions of the epidermis were prepared and loaded onto the 10x genomics system for bar coding and cDNA library construction.

first: Rambi

last: Cardones

first: Yingai

last: Jin

first: Vaibhav

last: Jain

first: Emily

last: Hocke

first: Jason

last: Gibson

first: Simone

last: Gregory


title: Mechanism of cytarabine-induced neurotoxicity [amplicon-Seq]

city: Bethesda

first: Chuanyuan

last: Chen

state: MD

address: 9000 Rockville Pike, Building 37

department: National Cancer Institute

institute: National Institutes of Health

summary: Postmitotic neurons are known to harbor high levels of methylated cytosine and its oxidized intermediates such as 5hmC, but the functional relevance of these epigenetic modifications of DNA are poorly understood. We show that some but not all cytidine analogs, such as cytarabine, cause DNA double strand breaks (DSB) during TET-mediated active 5mC demethylation by interrupting TDG-dependent base excision repair. These DSBs are frequently converted into indels and translocations by DNA ligase 4. In vivo, Purkinje and Golgi cells in the cerebellum are the only neuronal populations that exhibit high levels of DNA damage to cytarabine. In Purkinje cells, TET targets gene bodies with the highest expression marked by enhancer-associated histone modifications. Many of these genes control movement coordination which explains the long recognized cerebellar neurotoxicity of cytarabine. We show that other cytidine analogs, such as gemcitabine cause only single strand breaks in neurons, which are repaired by DNA ligase 3 with minimal toxicity. Our findings uncover a mechanistic link between TET-mediated DNA demethylation, base excision repair and gene expression in neurons and provide a rational explanation for the different neurotoxicity profiles of an important class of antineoplastic agents.

overall_design: The high-throughput experiments used in this study included a CRISPR interference screen in iPSC-derived neurons; SAR-seq in iPSC-derived neurons; S1/END-seq in iPSC-derived neurons, cortical neurons, and Purkinje neurons; LAM-HTGTS in iPSC-derived neurons; targeted deep sequencing (amplicon-seq) in iPSC-derived neurons; ATAC-seq in Purkinje neurons; RNA-seq in iPSC-derived neurons, cortical neurons, Purkinje and Golgi neurons; and CUT&RUN in Purkinje and Golgi neurons; Pyridine borane sequencing (PS-seq) in iPSC-derived neurons and Purkinje neurons.

first: Jia-Cheng

last: Liu

first: Dongpeng

last: Wang

first: Elsa

last: Callen

first: Santiago

last: Noriega

first: Yafang

last: Shang

first: David

last: Schürmann

first: Yawei

last: Song

first: Gokul N

last: Ramadoss

first: Raj

last: Chari

first: Nancy

last: Wong

first: Yongge

last: Zhao

first: Peter

last: Aplan

first: Nathaniel

last: Heintz

first: Anjana

last: Rao

first: Peter J

last: McKinnon

first: Keith

last: Caldecott

first: Primo

last: Schär

first: Feilong

last: Meng

first: Ferenc

last: Livak

first: Wei

last: Wu

first: Andre

last: Nussenzweig


title: Mechanism of cytarabine-induced neurotoxicity [SAR-Seq]

first: Chuanyuan

last: Chen

first: Jia-Cheng

last: Liu

first: Dongpeng

last: Wang

first: Elsa

last: Callen

first: Santiago

last: Noriega

first: Yafang

last: Shang


title: Mechanism of cytarabine-induced neurotoxicity [CUT&Run]

first: David

last: Schürmann

first: Yawei

last: Song

first: Gokul N

last: Ramadoss

first: Raj

last: Chari

first: Nancy

last: Wong

first: Yongge

last: Zhao


title: Mechanism of cytarabine-induced neurotoxicity [END-Seq]

first: Peter

last: Aplan

first: Nathaniel

last: Heintz

first: Anjana

last: Rao

first: Peter J

last: McKinnon

first: Keith

last: Caldecott

first: Primo

last: Schär


title: Mechanism of cytarabine-induced neurotoxicity [CRISPR Screen]

first: Chuanyuan

last: Chen

first: Jia-Cheng

last: Liu

first: Feilong

last: Meng

first: Ferenc

last: Livak

first: Wei

last: Wu

first: Andre

last: Nussenzweig


title: Mechanism of cytarabine-induced neurotoxicity [PS-Seq]

first: Dongpeng

last: Wang

first: Elsa

last: Callen

first: Santiago

last: Noriega

first: Yafang

last: Shang

first: David

last: Schürmann

first: Yawei

last: Song


title: The methyltransferases METTL7A and METTL7B confer resistance of cancer cells to thiol-based histone deacetylate inhibitors

first: Pedro

last: Batista

address: 37 Convent Street Bldg 37

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

overall_design: Refer to individual Series


title: Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques

city: Xi'an

first: Beibei

last: Yu

state: Shannxi

address: No. 157, Xiwu Road, Xincheng District, Xi'an City, Shaanxi Province

institute: Xijing hospital

summary: Antler blastema progenitor cell (ABPC) is a novel type of skeletal stem cells with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) can strongly rejuvenate aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating signals in EVsABPCs, which exhibited a robust in vitro ability to rejuvenate senescent bone marrow stromal stem cells. In vivo, EVsABPCs increased bone mineral density in femur by 2.4-fold in mice, and 1.53-fold in rhesus macaques. Besides, intravenous EVsABPCs significantly outperformed fetal-EVsBMSCs in improving physical performance, reducing systemic inflammation and rejuvenating major tissues of aged mice, with no observed immunological side effects. Notably, EVsABPCs showed similar rejuvenating effects in old rhesus macaques as in elderly mice. These findings suggest that ABPC is a novel and practical source of EVs containing unique rejuvenating factors and has considerable translational value for anti-aging interventions, particularly rejuvenation of aging bones.

overall_design: Three monkeys were randomly divided into three groups, with three monkeys in each group, namely the Vehicle group (injected with PBS); EVs FBMSC group (injection of EVs FBMSC); EVs ABPC group (injection of EVs ABPC)

first: Yiming

last: Hao


title: Simulated Microgravity Triggers a Membrane Adaptation to Stress in E. coli REL606

city: Houston

first: Brittney

last: Lozzi

state: TX

address: 1 Baylor Plaza

department: Cell & Gene Therapy

institute: Baylor College of Medicine

summary: Investigating the evolution of Escherichia coli in microgravity offers valuable insights into microbial adaptation to extreme environments. Here the effects of simulated microgravity (SµG) on gene expression  of E. coli REL606, a strain evolved terrestrially for 35 years is explored. We evaluated the transcriptomic changes for glucose-limited and glucose-replete conditions over 24 hours which illustrate that SµG increased the expression of stress response and cell membrane-related genes, particularly under glucose-limited conditions. A machine learning model predicted that glucose-limited SµG impacts the cellular membrane, while glucose-replete SµG also inhibits protein synthesis at stationary phase. These findings highlight the transcriptomic and physiological adaptations of E. coli to short term microgravity, offering a foundation for future research into the long-term effects of space conditions on bacterial evolution.

overall_design: To understand the effect of short-term exposure to microgravity in the REL606 strain of E. coli we grew samples for 24 hours in simulated microgravity conditions using vertical rotation. Control samples were grown in a horizontal rotating plane (rotating) and in a stationary fixture (static). Samples were further challenged by nutrient availability in glucose-limited and glucose-replete media. Samples were collected at initial, exponential, and stationary growth phase in biological quadruplicate and assays for transcriptomic changes via RNA-Seq.

first: Lea

last: Adepoju

first: Aubrie

last: O’Rourke


title: Mechanism of cytarabine-induced neurotoxicity [RNA-Seq]

first: Chuanyuan

last: Chen

first: Jia-Cheng

last: Liu

first: Gokul N

last: Ramadoss

first: Raj

last: Chari

first: Nancy

last: Wong

first: Yongge

last: Zhao

first: Peter

last: Aplan

first: Nathaniel

last: Heintz

first: Anjana

last: Rao

first: Peter J

last: McKinnon

first: Keith

last: Caldecott

first: Primo

last: Schär


title: Extracellular vesicles from antler blastema progenitor cells reverse bone loss and improve aging-related phenotypes in mice and macaques

first: Beibei

last: Yu

summary: Antler blastema progenitor cell (ABPC) is a novel type of skeletal mesenchymal stem cell with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) can strongly rejuvenate aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating molecules in EVsABPCs that differed from EVs of mouse bone marrow stromal stem cells (EVsBMSCs). EVsABPCs exhibited a robust in vitro ability to rejuvenate senescence BMSCs of aged mice and shift their molecular signature into a youthful state. In vivo, EVsABPCs increased bone mineral density in the femur by 2.4-fold in mice, and 1.53-fold in rhesus macaques. Besides, intravenous EVsABPCs significantly outperformed mouse fetal-EVsBMSCs in improving physical performance, reducing systemic inflammation, and rejuvenating major tissues of elderly mice, with no observed immunological side effects. Furthermore, EVsABPCs showed similar rejuvenating effects in old rhesus macaques as in elderly mice. Particularly, EVsABPCs resulted in remarkable improvements in brain structure and behaviors of elderly rhesus macaques, providing the first batch of evidence of EVs’ beneficial effects on aging brains in primates. These findings suggest that the ABPC is a novel and practical source of EVs containing a wealth of systemic rejuvenating factors and has considerable translational value for anti-aging interventions, particularly the rejuvenation of aging bones.

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus

overall_design: Antler blastema progenitor cells (ABPCs) were separated using a method described in our previous study 20. Single-cell suspensions of ABPCs comprising Dulbecco’s modified Eagle’s medium (DMEM; Gibco, 11965092), 1% penicillin-streptomycin (Gibco, 15140122), 0.1% mycoplasma removal agent and fetal bovine serum (FBS; Gibco, 10099141C) were seeded in 10 cm culture dishes at a density of 2 × 105 cells/cm2 and incubated at 37 °C in 5% CO2. After 24 h, non-adherent cells were removed, whereas attached cells were incubated further. When cellular growth reached 80–90% confluence, adherent cells were harvested and reseeded at a density of 2 × 105 cells/cm2 for further amplification. ABPCs of passages 6 to 10 (P6 to P10) were used for the experiments. Bone marrow stromal cells (BMSCs) were isolated from 18-month-old (A-BMSCs) and 10-day-old (F-BMSCs) male Sprague-Dawley rats. The proximal and distal metaphyses of femurs and tibias were cut and the bone marrow was flushed from the diaphyses with 10% FBS in phosphate buffer solution (PBS). A single-cell suspension comprising α-minimum essential medium (MEM α; Gibco, 12571063), 1% penicillin-streptomycin (Gibco, 15140122), 0.1% mycoplasma removal agent and FBS (Gibco, 10099141C) was seeded on a 10 cm culture dish at a density of 2 × 105 cells/cm2 and left to incubate at 37 °C in 5% CO2. After 24 h, non-adherent cells were removed, whereas attached BMSCs were incubated further. When cell growth reached 80–90% confluence, adherent cells were harvested and seeded at a density of 2 × 105 cells/cm2 for amplification. F-BMSCs and A-BMSCs of passages 6 to 10 (P6 to P10) were used for the experiments. The culture conditions for the two types of BMSCs (F-BMSCs and A-BMSCs) were identical.

first: Jinghui

last: Huang


title: Mechanism of cytarabine-induced neurotoxicity [HTGTS]

first: Dongpeng

last: Wang

first: Elsa

last: Callen

first: Santiago

last: Noriega

first: Yafang

last: Shang

first: David

last: Schürmann

first: Yawei

last: Song

first: Feilong

last: Meng

first: Ferenc

last: Livak

first: Wei

last: Wu

first: Andre

last: Nussenzweig


title: RNA-seq analysis of RNA polymerase I inhibitor in A375 melanoma cells.

city: BALTIMORE

first: Marikki

last: Laiho

address: 1550 Orleans St

department: Department of Radiation Oncology and Molecular Radiation Sciences

institute: Johns Hopkins University

summary: Ribosome biosynthesis is essential for cancer growth and proliferation. This dependency is therapeutically exploitable by blocking the rate-limiting step, RNA polymerase I (Pol I) transcription. Here we investigated the effects of RNA Pol I inhibitor on expression of mRNA genes.

overall_design: We treated A375 melanoma cells with 1 microM BMH-21 for 24 hrs. RNA sequencing (RNA-seq) was performed using three biological replicates.

first: Wenjun

last: Fan

first: Hester

last: Liu


title: Mechanism of cytarabine-induced neurotoxicity [ATAC-Seq]

first: Chuanyuan

last: Chen

first: Jia-Cheng

first: Gokul N

last: Ramadoss

first: Raj

last: Chari

first: Nancy

last: Wong

first: Yongge

last: Zhao

first: Peter

last: Aplan

first: Nathaniel

last: Heintz

first: Anjana

last: Rao

first: Peter J

last: McKinnon

first: Keith

last: Caldecott


title: RNA-seq analysis of RRN3 knockdown in HCT116 cells

summary: Ribosome biosynthesis is essential for cancer growth and proliferation. This dependency is therapeutically exploitable by blocking the rate-limiting step, RNA polymerase I (Pol I) transcription. Here we investigated the effects of knockdown RNA Pol I component RRN3. expression of mRNA genes.

overall_design: We silenced RRN3 in HCT116 cells by siRNA. RNA sequencing (RNA-seq) was performed using three biological replicates.


title: RNA-seq analysis of RNA polymerase I inhibitor in HCT116 cells

overall_design: We treated HCT116 cells with 1 microM BMH-21 for 24 hrs. RNA sequencing (RNA-seq) was performed using three biological replicates.


title: Alternative splicing in mechanically stretched podocytes as a model of glomerular hypertension

city: Hamburg

first: Olga

last: Tsoy

state: Hamburg

address: Alber-Einstein Ring 8-10

institute: Universität Hamburg

summary: Alterations in pre-mRNA splicing play an important role in disease pathophysiology. However, the role of alternative splicing (AS) for podocytes in hypertensive nephropathy (HN) has not been investigated. Here we identifiedAS events that play a role in the development and progression of HN. For this, murine podocytes were exposed to mechanical stretch to model HN, after which proteins and mRNA were measured by proteomics, RNA-Seq, and analyzed by several AS detection tools. We found two Shroom3 isoforms that showed significant changes in expression upon mechanical stretch, which was verified by qRT-PCR and in-situ hybridization. Furthermore, we observed an expression switch of two Myl6 isoforms after mechanical stretch. This switch is accompanied by a change in a C-terminally located amino acid sequence. In summary, mechanical stretch of cultured podocytes is an excellent model to simulate hypertensive nephropathy. In depth RNA-Seq analysis disclosed alternative splicing events and differential gene expression, which together with protein regulation improve the understanding of the pathophysiology of hypertension-induced nephropathy.

overall_design:
To investigate the role of alternative splicing in glomerular hypertension we performed mechanical stress experiments on conditionally immortalised podocytes (SVI; CLS Cell Line Service GmbH, Eppelheim, Germany)
Differentiated mouse podocytes were seeded on flexible silicon membranes of a six well plate (Bioflex, Flexcell® International Corporation, Burlington, NC, USA).
Pressure amplitude was chosen to give a maximum up- and downward deflection of the membrane center of 6 mm (low stretch) and a higher amplitude (8 mm).
We then performed gene expression profiling using the data from RNA-Seq of unstretched, high-stretched, and low stretched podocytes.
Comparative gene expression and alternative splicing analysis of unstretched podocytes versus low-stretch and unstretched podocytes and high-stretch

first: Francescapaola

last: Mattias

first: Elke

last: Hammer

first: Alexander

last: Gress

first: Stefan

last: Simm

first: Chit

last: Lio

first: Sabine

last: Ameling

last: Kalinina

first: Kerstin

last: Amann

first: Ulrich

last: Wenzel

first: Karlhans

last: Endlich

first: Jan

last: Baumbach

first: Uwe

last: Völker

first: Nicole

first: Felix

last: Kliewe


title: The molecular basis for the attenuation of the yellow fever 17D vaccine [wtYFV_RNAseq]

city: Princeton

first: Jiayu

last: Zhang

state: NJ

address: 119 Lewis Thomas Laboratory, Washington Road

department: Molecular Biology

institute: Princeton

summary: Yellow fever virus, a prototypical member of the Flaviviridae family, is a small single-stranded, positive sense enveloped RNA virus  causing viscerotropic, frequently fatal disease. Serial passaging of the virulent YFV Asibi strain in the 1930s yielded the YFV17D strain which remains one of the most effective vaccines ever developed. Remarkably, YFV17D and the virulent parental genome differ only by 68 nucleotides leading to 32 amino acid changes. However, it remains largely unknown which of these sequence differences are responsible for attenuation. Here, we demonstrate that while synonymous mutations are highly conserved across pathogenic YFVs they do not contribute to the characteristic host responses elicited by 17D or virulent viruses. Using a highly modular combinatorial genetic approach we identified key genetic elements in the YFV envelope and non-structural 2A (NS2A) proteins that govern the virus’ ability to  spread and suppress host responses.. Introducing these mutations into infectious clones of other YFV genomes results in viral attenuation in vitro and in vivo. Collectively, our results define the genetic basis for YFV17D attenuation and highlight a general approach for creating live-attenuated vaccines for other pathogenic viruses.

overall_design: Huh7 cells were infected with reporter-YFVs, sorted at 48 hours post infection, and subjected for comparative gene expression profiling (RNA-seq).

first: Aaron

last: Lin

last: Ploss


title: The molecular basis for the attenuation of the yellow fever 17D vaccine [chimerasYFVs_RNAseq]


title: UCPVax, a CD4 helper peptide vaccine induces polyfunctional Th1 cells, antibody response and epitope spreading to improve antitumor immunity  [scRNA-seq]

city: Besançon

first: Olivier

last: Adotévi

state: Franche-Comté

address: 8 rue du Dr JFX Girod

department: Oncology

country: France

institute: Université de Franche-Comté

summary: The induction of an antitumor CD4+ T helper response is essential for the efficacy of therapeutic cancer vaccines. However, few vaccines are specifically designed to target CD4+ T cells in human cancers. Here, we characterize the immune mechanisms of UCPVax, a helper peptide vaccine derived from telomerase. Ex vivo immune profiling of peripheral blood from 60 patients with advanced lung cancer reveals that UCPVax selectively activates CD4+ T cells in vivo across a broad HLA-DR restriction. The vaccine elicits a synergistic immune triad including cytokine-polyfunctional CD4+ Th1 cells, epitope spreading, and antibody response, contributing to effective tumor control. Single-cell analysis further demonstrates that UCPVax drives CD4+ T cells toward effector-memory and cytolytic differentiation. Thus, the vaccine-induced CD4+T cells trigger a broad and durable antitumor immunity. These findings highlight UCPVax as an off-the-shelf helper platform to enhance therapeutic cancer vaccine efficacy.

overall_design:
Vaccine-induced CD4+Th1 cells were characterized using single-cell RNA sequencing. UCP-specific CD4+ T cells (IFN-γ+CD4+) were sorted from PBMC in four vaccinated patients (P023, P005 and pooled patient 020+037). PBMC collected before vaccination in one patient (P023) was used as control, PBMC collected after 12 months of treatment for P023 was also used.

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Submitter states that missing raw files (GSM8978585, GSM8978586) are due to file loss.
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first: Caroline

last: Laheurte

first: Babacar

last: Ndao

first: Marine

last: Malfroy

first: Lise

last: Queiroz

first: Evan

last: Seffar

first: Raphael

last: Genolet


title: UCPVax, a CD4 helper peptide vaccine induces polyfunctional Th1 cells, antibody response and epitope spreading to improve antitumor immunity  [TCR-seq]

overall_design: TCRβ sequencing was perfomed on vaccine-induced CD4+T cells from four patients (P023, P005, P20, P37). Negative fraction (Bulk CD4) was collected in these patients as control. Bulk CD4 collected before vaccination in one patient (P023) was also used as reference.


title: The molecular basis for the attenuation of the yellow fever 17D vaccine [SHAPEmap]

overall_design: Huh7 cells were infected with YFVs, treated with SHAPE chemical, 2-aminopyridine-3-carboxylic acid imidazolide (2A3), and subjected for selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP).

first: Alexander


title: ChIP-seq analysis of RNA polymerase I inhibitor effect on Pol I and Pol II binding

first: Marikki

last: Laiho

state: Maryland

summary: Ribosome biosynthesis is essential for cancer growth and proliferation. This dependency is therapeutically exploitable by blocking the rate-limiting step, RNA polymerase I (Pol I) transcription. Here we investigated the effects of RNA Pol I inhibitor on binding of Pol I RPA1 and Pol II Rpb1 on genomic DNA.

overall_design: We treated LNCaP prostate cancer cells with either DMSO vehicle or 1 microM BMH-21 for 6 hrs.

first: Wenjun

last: Fan

first: Hester

last: Liu


title: RNA-seq analysis of RNA polymerase I inhibitor in A375 melanoma cells

overall_design: We treated A375 melanoma cells with 1 microM BMH-21 for 6 hrs. RNA sequencing (RNA-seq) was performed using three biological replicates.


title: RNA-seq analysis of RNA polymerase I inhibitor in p53 null HCT116 colon adenocarcinoma cells.

overall_design: We treated p53 null HCT116 cells with 1 microM BMH-21 for 6 hrs. RNA sequencing (RNA-seq) was performed using three biological replicates.


title: RNA-seq analysis of parent, RPL22L1 knockout and RPL22 reconstituted HCT116 cells.

summary: Ribosome biosynthesis is essential for cancer growth and proliferation. This dependency is therapeutically exploitable by blocking the rate-limiting step, RNA polymerase I (Pol I) transcription. We discovered that RPL22 and RPL22L1 were markers for sensitivity to Pol I inhibition. We discovered that their genetic manipulation prominently altered the expression and splicing of a multitude of mRNAs.

overall_design: We generated RPL22L1 knockout and RPL22-reconstituted HCT116 cells. RNA sequencing (RNA-seq) was performed with three replicates for each group. Differential expression and alternative splicing were analyzed.


title: RNA-seq analysis of RNA polymerase I inhibitor in p53 proficient HCT116 colon adenocarcinoma cells

overall_design: We treated p53 proficient HCT116 cells with 1 microM BMH-21 for 6 hrs. RNA sequencing (RNA-seq) was performed using three biological replicates.


title: GoldCLIP-seq analysis of RPL22HaloTag and RPL22L1HaloTag RNA-binding

summary: Ribosome biosynthesis is essential for cancer growth and proliferation. This dependency is therapeutically exploitable by blocking the rate-limiting step, RNA polymerase I (Pol I) transcription. Here we investigated the ability of RPL22 and RPL22L1 to interact with cellular RNAs. We discovered that Pol I inhibition prominently altered splicing of hundreds of mRNAs. RPL22 and RPL22L1 resided at splice junctions and interacted with hundreds of coding and non-coding RNAs in addition to the 28S rRNA. Further, their genetic manipulation prominently altered the splicing of a multitude of mRNAs.

overall_design: We generated RPL22-HaloTag and RPL22L1-HaloTag HCT116 cells. We conducted RNA-pulldowns using GoldCLIP-RNA sequencing.


title: Differences in mitotic chromosome organization between cell types and species [ATAC-Seq]

city: München

first: Marlies

middle: E

last: Oomen

address: Feodor-Lynen-Strasse 21

department: Institute of Epigenetics and Stem Cells

institute: Helmholtz Zentrum München

summary: We performed ATAC-seq on mouse myoblast cells C2C12 in interphase and mitosis to observe footprinting on CTCF sites

overall_design: ATAC-seq performed with asynchronized and mitotically synchronized mouse myoblasts (C2C12)

first: Pablo

last: Navarro

first: Job

last: Dekker


title: Differences in mitotic chromosome organization between cell types and species [Hi-C]

summary: We performed Hi-C analysis of different mouse and human cell types to observe chromosome organization in mitosis with and without retained CTCF binding

overall_design: Hi-C performed with asynchronized and mitotically synchronized mouse myoblasts (C2C12), mouse embryonic stem cells (E14TG2a)  and human HeLa-S3 cells


title: Differences in mitotic chromosome organization between cell types and species

overall_design: Refer to individual Series


title: Targeting AURKA to induce synthetic lethality in CREBBP-deficient DLBCL via attenuation of MYC expression

city: Guangzhou

first: Jianfeng

last: Chen

address: 651East Dongfeng Road

institute: SYSUCC

summary:
Loss-of-function mutations in CREBBP, which encodes for a histone acetyltransferase, occur frequently in diffuse large B-cell lymphoma (DLBCL), highlighting CREBBP deficiency as an attractive therapeutic target. Using established isogenic DLBCL cell models, we demonstrated that CREBBP-deficient cells are selectively vulnerable to AURKA inhibition. Mechanistically, we found that co-targeting CREBBP and AURKA suppressed MYC transcriptionally and post-translationally to induce replication stress and apoptosis. Inhibition of AURKA dramatically decreased MYC protein level in CREBBP-deficient cells, implying a dependency on AURKA to sustain MYC stability. Furthermore, in vivo studies showed that pharmacological inhibition of AURKA was efficacious in delaying tumor progression in CREBBP-deficient cells and was synergistic with CREBBP inhibitors in CREBBP-proficient cells. Our study sheds light on a novel synthetic lethal interaction between CREBBP and AURKA, indicating that targeting AURKA represents a potential therapeutic strategy for high-risk DLBCL harboring CREBBP inactivating mutations.
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for CREBBP and H3K27ac in SC1 cells.

overall_design: Yichen,Sun

first: Jing

middle: H

last: Hong

first: Kelila

last: Chai


title: Tp53 and Tet2 mutations cooperatively transform GMP (RNA-Seq)

status: Public on May 12 2025

city: Columbus

first: Pu

last: Zhang

address: 1258 Bunkerhill Blvd, AptB

institute: Ohio State University

summary: Mutations and deletions in TP53 are associated with adverse outcome in patients with myeloid malignancies and developing improved therapies for TP53-mutant leukemias is of urgent need. Here we identify mutations in TET2 as the most commonly co-existing mutation in TP53 mutant acute myeloid leukemia (AML) patients. Combined hematopoietic-specific deletion of TET2 and TP53 in mice enhanced self-renewal compared to deletion of either gene alone. Tet2/Tp53 double knockout mice developed serially transplantable AML. Both mice as well as patients with AML and combined TET2/TP53 alterations upregulated innate immune signaling in malignant cells. Mice with TET2/TP53 loss had expansion of monocytic myeloid-derived suppressor cells which impaired T cell proliferation. Moreover, patients and mice with TP53/TET2 double mutant AML upregulated TIGIT ligands CD155 on malignant cells. TIGIT blocking antibodies augmented the ability of NK cells to kill Tet2/Tp53 double mutant AML cells, reduced leukemic burden, and extended the survival of TET2/TP53 double knockout mice. These data thereby identify a previously unexplored link between TET2 and TP53 mutations and highlight therapeutic means to overcome the immunosuppressive bone marrow environment in this adverse subtype of AML.

overall_design: To understand the molecular mechanisms underlying AML transformation upon combined mutation in TET2 and TP53, we performed limiting cell RNA-seq of GMP (lin-cKit+Sca-1-CD16/32+CD34+) cells from diseased Vav-cre Tet2fl/fl Tp53fl/fl mice developing AML and age-matched Vav-cre Tp53fl/fl, Vav-cre Tet2 fl/fl, and WT mice.

first: Omar

last: Abdel-Wahab

first: Rosa

last: Lapalombella


title: p300/CBP-catalyzed acetylation safeguards minor zygotic genome activation via activating DUX [RNA-Seq]

city: Hangzhou

first: Lieying

last: Xiao

state: 浙江省

address: Nongshenghuan Building E, Zhejiang University, Hangzhou, Zhejiang

institute: Zhejiang University

summary: Maternal-deposited factors initiate zygotic genome activation (ZGA), driving the maternal-to-zygotic transition; however, the coordination between maternal coactivators and transcription factors (TFs) in this process remains unclear. In this study, by profiling the dynamic landscape of p300 during mouse ZGA, we reveal its role in promoting RNA polymerase II (Pol II) pre-configuration at ZGA gene regions and sequentially establishing enhancer activity and regulatory networks. Moreover, p300/CBP-catalyzed acetylation drives Pol II elongation and minor ZGA gene expression by inducing pivotal TFs such as Dux. Remarkably, the supplementation of exogenous Dux rescues ZGA failure and developmental defects caused by the loss of p300/CBP acetylation. DUX functions as a pioneer factor, guiding p300 and Pol II to minor ZGA gene regions and activating them in a manner dependent on the non-catalytic functions of p300/CBP. Together, our findings reveal a mutual dependency between p300/CBP and DUX, highlighting their coordinated role in regulating minor ZGA activation.

overall_design: To investigate the role of p300/CBP during mouse zygotic genome activation, we performed RNA-seq, p300 and Pol II Stacc-seq, H3K27ac ChIP-seq, and ATAC-seq in control (DMSO), A485-treated (A485), and Dux-rescued (A485+Dux) embryos at the late 1-cell, early 2-cell, and late 2-cell stages.

first: Hao

last: Jin

first: Kun


title: Sex-dependent Influence of LMAN1 on Allergen-induced Airway Hyperresponsiveness

city: Orlando

first: Justine

middle: T.

last: Tigno-Aranjuez

state: FL

address: 6900 Lake Nona Blvd., BSBS Bldg, Rm 370

department: BSBS, Immunity and Pathogenesis Division

institute: University of Central Florida

summary: Allergic asthma is a chronic inflammatory disease of the airways characterized by a type 2-high adaptive immune response towards common aeroantigens such as dust mite, pollen and animal dander. Despite the advances made towards translation of various biologics into the clinic, the limited efficacy of these therapies in certain populations, combined with the ineligibility of some patients for treatment (clinically or economically), have led to the continued need for the development of more widely effective allergic asthma therapies. Our lab previously identified lectin mannose-binding 1 (LMAN1) as a novel receptor for house dust mite (HDM) and showed that in vitro, LMAN1 downregulated inflammatory NF-κB signaling in DCs in response to HDM. In this follow-up work, we investigated the in vivo relevance of LMAN1 by subjecting LMAN1 knockout (KO) mice and wild type (WT) littermate controls to a model of HDM-induced allergic asthma. Surprisingly, we discovered that loss of LMAN1 led to opposing effects on airway hyperresponsiveness (AHR) which were dependent on the sex of the mice.  HDM-treated female LMAN1 KO mice showed increased AHR, while HDM-treated male KO mice showed decreased AHR, compared with their WT counterparts. We further identified the features of HDM-induced asthma which may account for the gender-biased effects of LMAN1 on lung function. This work not only highlights the complexity of the loss of LMAN1 in vivo but also suggests that such sex-dependent responses should be taken into consideration when pursuing LMAN1 as a therapeutic target for treatment of allergic asthma.

overall_design: Primary murine tracheal epithelial cell cultures (MTECs) were established from WT and LMAN1 KO mice of both sexes. Cultures were left untreated or treated with HDM overnight, prior to extraction of RNA for RNA sequencing.

first: Lindsay

last: Swaby

first: Faith

last: Sauber

first: Madelyn

last: Miller

first: Mylena

middle: C

last: Xavier

first: Wesley

last: Lim

first: Peter

middle: D

last: Poulson

first: Xiang

last: Zhu

first: Bin


title: Targeting CDK4/6 impairs RB1/E2F activity to overcome the resistance to selinexor in Nature killer/T-cell lymphoma

first: Jianfeng

summary: XPO1 is frequently overexpressed in multiple hematological malignancies, highlighting the attractiveness of targeting XPO1 as a therapeutic strategy. However, the therapeutic potential of XPO1 inhibition in NKTL was still not well documented. Here, we demonstrated that XPO1 is highly expressed in NKTL and is correlated with poor prognosis, suggesting that XPO1 is a potential target in NKTL. In addition, we identified YY1 as a transcriptional factor that bound to XPO1 promoter to activate its expression. Functional studies revealed that pharmacological inhibition of XPO1 using selinexor effectively blocks CDK4/6-pRB-E2F-c-Myc signaling, resulting in cell cycle arrest and apoptosis in sensitive cells. Transcriptomic analysis identified that dysfunction in cell cycle machinery may contribute to selinexor resistance, as resistant cells restore the expression of cycle-related genes to evade cell death. High-throughput screening utilizing a panel of 130 cell cycle inhibitors identified CDK4/6 inhibitors as sensitizers to selinexor in resistant cells. Mechanistically, the combination of CDK4/6 inhibitors and selinexor led to an enhanced inhibition of pRB-E2F-c-Myc signaling. Additionally, compassionate use of selinexor in combination with chemotherapy (gemcitabine, oxaliplatin) in three Refectory/Relapsed (R/R) NKTL patients achieved favorable clinical outcomes. Our data unveil a novel mechanism by which XPO1 inhibition blocks CDK4/6-pRb-E2F-c-Myc signaling, providing a rationale for the combination of CDK4/6 with XPO1 inhibitors for NKTL treatment.

overall_design: RNA-seq for YT  treated with DMSO or selinexor, while NK-S1 treated with DMSO, selinexor, abemaciclib or combination (duplicate).

first: Yali

last: Wang

first: Yan

last: Gao

first: Jing

last: Tan


title: Tp53 and Tet2 mutations cooperatively transform progenitors (RNA-Seq)

first: Pu

summary: Mutations and deletions in TP53 are associated with adverse outcome in patients with myeloid malignancies and developing improved therapies for TP53-mutant leukemias is of urgent need. Here we identify mutations in TET2 as the most commonly co-existing mutation in TP53 mutant acute myeloid leukemia (AML) patients. Combined hematopoietic-specific deletion of TET2 and TP53 in mice enhanced self-renewal compared to deletion of either gene alone. Tet2/Tp53 double knockout mice developed serially transplantable AML. Both mice as well as patients with AML and combined TET2/TP53 alterations upregulated innate immune signaling in malignant cells. Mice with TET2/TP53 loss had expansion of monocytic myeloid-derived suppressor cells which impaired T cell proliferation. Moreover, patients and mice with TP53/TET2 double mutant AML upregulated TIGIT ligands CD155 and CD112 on malignant cells. TIGIT blocking antibodies augmented the ability of NK cells to kill Tet2/Tp53 double mutant AML cells, reduced leukemic burden, and extended the survival of TET2/TP53 double knockout mice. These data thereby identify a previously unexplored link between TET2 and TP53 mutations and highlight therapeutic means to overcome the immunosuppressive bone marrow environment in this adverse subtype of AML.

overall_design: To understand the molecular mechanisms underlying AML transformation upon combined mutation in TET2 and TP53, we performed bulk RNA-seq of Lin-cKIT+ myeloid progenitors (LK) and Lin-cKIT+Sca-1+ (LSK) cells from diseased Vav-cre Tet2fl/fl Tp53fl/fl mice developing AML and age-matched Vav-cre Tp53fl/fl, Vav-cre Tet2 fl/fl, and WT mice.

first: Zhang

last: Pu

first: Campbell

last: Moray

first: Lapalombella

last: Rosa


title: OTUD3  prevents ulcerative colitis by modulating microbiota-mediated STING activation (part 5)

first: Daisuke

last: Motooka

address: 3-1, Yamadaoka

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

summary: Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are suggested to play crucial roles in the pathogenesis of UC. However, the influences of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remain poorly understood. Here, we reveal that OTUD3 suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3’3’-cGAMP) by deubiquitinating stimulator of interferon genes (STING) in the colon. Sting deficiency ameliorated dextran sodium sulfate-induced colitis in Otud3-/- mice. In addition, mice harboring an UC risk missense variant in the Otud3 gene showed pathological features of UC in the colon after transplantation of a fecal microbiome with the potential to produce excessive cGAMP from UC patients. Collectively, these results demonstrate the critical role of OTUD3 in the maintenance of intestinal homeostasis and highlight one mechanism of the interaction between the host (OTUD3 in fibroblasts) and microbiota (STING agonist) in UC development.

overall_design: 7AAD-EpCAM- cells were isolated from the colon of Otud3 f/f and Pdgfra-cre; Otud3 f/f mice administered 1% dextran sodium sulfate for 7 days.

first: Bo

last: Li

first: Taiki

last: Sakaguchi

last: Okuzaki


title: Identification of medication-microbiome interactions that impact gut infection

city: West Haven

first: Aman

last: Kumar

state: CT

address: 840 West Campus Drive

institute: Yale Universitry

summary: The majority of people in the U.S. manage health through at least one prescription drug. Drugs classified as non-antibiotics can adversely affect the gut microbiome and disrupt intestinal homeostasis. Here, we identified medications associated with an increased risk of GI infections across a population cohort of more than 1 million individuals monitored over 15 years. Notably, the cardiac glycoside digoxin and other drugs identified in this epidemiological study are sufficient to alter microbiome composition and risk of Salmonella enterica subsp. Typhimurium (S. Tm) infection in mice. The impact of digoxin treatment on S. Tm infection is transmissible via the microbiome, and characterization of this interaction highlights a digoxin-responsive b-defensin that alters microbiome composition and consequent immune surveillance of the invading pathogen. Combining epidemiological and experimental approaches thus provides an opportunity to uncover drug-host-microbiome-pathogen interactions that increase infection risk in human populations.

overall_design: We characterized the effect of digoxin on gene expression of mice ileum tissue.  We treated conventional C57BL/6NTac mice with 4 doses of digoxin orally over two days. Mice were sacrificed at D0 time point and approximately 2cm of terminal ileum tissue was collected. RNA was extracted and samples were sent for bulk-RNA sequencing. PBS dissolved in 5% DMSO was used as vehicle controls. Three biological replicates were used for the experiment

first: Andrew

last: Goodman


title: Amino acid changes in two viral proteins drive attenuation of the yellow fever 17D vaccine

first: Jiayu

last: Zhang

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

sample_organism:
Homo sapiens
Yellow fever virus

platform_organism:
Homo sapiens
Yellow fever virus


title: p300/CBP-catalyzed acetylation safeguards minor zygotic genome activation via activating DUX [ChIPseq_ATAC-seq_Stacc-seq]

first: Lieying

last: Xiao

first: Hao

last: Jin

first: Kun


title: OTUD3  prevents ulcerative colitis by modulating microbiota-mediated STING activation (part 4)

overall_design: EpCAM-CD45-CD31-gp38+ stromal cells were isolated form the colon of healthy control and Pdgfr1-cre; Otud3 f/f mice.


title: Aberrant Phase Separation of two PKA RIbeta Neurological Disorder Mutants Leads to Mechanistically Distinct Signaling Deficits

city: La Jolla

first: Emily

last: Pool

state: California

address: 9500 Gilman Dr.

department: Pharmacology

institute: UCSD

summary: Spatiotemporal regulation of key-node signaling molecules, such as 3’,5’-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), is critical for normal cell physiology and susceptible to dysregulation in disease. Liquid-liquid phase separation (LLPS) is broadly recognized as a fundamental component of signal regulation, yet the connections between physiological and disease-linked biomolecular condensates are not well understood. Here, we show that an understudied, brain-specific PKA regulatory subunit, RIβ, forms biomolecular condensates with distinct features from the ubiquitous isoform, RIα. We demonstrate that two RIβ mutants linked to neurodegenerative (L50R) or neurodevelopmental (R335W) pathologies produce aberrant condensates which trap the PKA catalytic subunit within a gel-like matrix or cAMP-insensitive holoenzyme complex, respectively. RIβL50R condensates, in particular, lead to disrupted spatiotemporal control of PKA signaling and diminished PKA activity, resulting in phenotypic hallmarks of neurodegeneration. Our work highlights the functional importance of biomolecular condensates and the critical link between dysregulated LLPS and neurological disorders.

overall_design: We transiently transfected PKA RIalpha knockout HEK293T cells with RIbeta-mRuby2, the L50R neurodegenerative disease variant, or mRuby2 fluorescent protein alone (as a control), in triplicate. Transfected cultures were harvested to assess transcriptional differences between wild-type and L50R variant RIbeta.

first: Alexander

last: Glebov-McCloud

first: Ha Neul

last: Lee

first: Julia

last: Hardy

first: Valeria

last: Pane

first: Friedrich

middle: W

last: Herberg

first: Susan

middle: S

last: Taylor

first: Sohum

last: Mehta

first: Stefan

last: Strack

first: Jin


title: Microrchidia ATPases and 6mA DNA demethylase ALKBH1 act antagonistically on PRC2 to control gene expression for stress tolerance

city: Wuhan

first: Qingxiao

last: Jia

state: Hubei

address: No.1,Shizishan Street

institute: HZAU

type: Methylation profiling by high throughput sequencing

summary: The Microrchidia (MORC) ATPases are required for heterochromatin condensation and transposable element silencing in plants and animals. In plants, MORC proteins have been shown to be required for the efficient RNA-directed DNA methylation (RdDM) at specific chromatin regions and have a function in plant response to biotic stress. Here we provide first evidence linking MORC proteins with Polycomb-Repressive Complex 2 (PRC2). We show that rice MORC proteins interact with PRC2 proteins and are required for efficient PRC2-binding to genomic targets for H3K27me3 and gene repression. This function of MORC proteins is counteracted by ALKBH1, a DNA 6mA demethylase previously shown to impair PRC2 binding to a subset of the target. We find that OsMORC6b binding is enriched at gene transcriptional start sites, which overlaps largely with that of the PRC2 protein EMF2b and co-localizes with fine scale chromatin boundaries delimitating genic H3K27me3 domains from open chromatin. We further show that rice MORC proteins are required to maintain RdDM at CHH sequences at the upstream promoter region and H3K27me3 at the downstream body region for gene repression. These findings uncover novel function for MORC in chromatin regulation and have implications for MORC protein function in other eukaryotic organisms.

overall_design: Through various high-throughput data analyses, the functions of the rice MORC proteins in chromatin were identified.

first: Xinran

first: Wentao

last: Wang

first: Dao-Xiu

last: Zhou


title: OTUD3  prevents ulcerative colitis by modulating microbiota-mediated STING activation (part 2)

first: Daisuke

last: Motooka

overall_design: Colonic Ly6Chigh fibroblasts stimulated with or without 3’3’-cGAMP in the presence or absence of DCPIB or sulfasalazine for 6 h.

first: Bo

last: Li

last: Okuzaki


title: OTUD3  prevents ulcerative colitis by modulating microbiota-mediated STING activation (part 3)

overall_design: Colonic Ly6Chigh fibroblasts stimulated with or without 3’3’-cGAMP in the presence or absence of DCPIB or A740003 for 6 h.


title: OTUD3  prevents ulcerative colitis by modulating microbiota-mediated STING activation (part 1)

overall_design: PDGFRalpha+ Ly6C+ fibroblasts were isolated form healthy colon.


title: Dynamic Control of Argonautes by a Rapidly Evolving Immunological Switch

status: Public on May 11 2025

city: Tel Aviv

first: Hila

last: Gingold

address: 30 Haim Levanon Street

country: Israel

institute: Tel-Aviv University

type: Non-coding RNA profiling by high throughput sequencing

summary: Small RNAs, coupled with Argonuate proteins (AGOs), regulate diverse biological processes, including immunity against parasitic genetic elements. C. elegans possesses an expanded repertoire of at least 19 AGOs functioning in an intricate gene regulatory network. Despite their crucial roles, little is known about the regulation of AGOs, and whether their expression levels, tissue specificity, and functions change in response to genetic perturbations or environmental triggers. Here, we report that PALS-22, a member of an unusually expanded protein family in C. elegans, acts as a negative regulator of antiviral RNAi involving the RIG-I homolog. The loss of pals-22 leads to enhanced silencing of transgenes and endogenous dsRNAs. We found that PALS-22 normally suppresses the expression of two AGOs, VSRA-1 and SAGO-2, which are activated by bZIP transcription factor ZIP-1. When pals-22 is eliminated, vsra-1 and sago-2 are upregulated. These AGOs in turn play key roles in defense against foreign genetic elements and intracellular pathogens, respectively. Surprisingly, while in pals-22 mutants immune genes functioning in the intracellular pathogen response (IPR) are upregulated, removing SAGO-2 or the RNA-dependent RNA polymerase RRF-3 in these mutants leads to the downregulation of these genes. This observation contrasts with the typical gene-silencing role of siRNAs. Finally, by analyzing C. elegans wild isolates and lab reference strains, we demonstrate that PALS-22 regulates the expression of several germline AGOs, affecting germline mortality and transgenerational epigenetic inheritance. In summary, PALS-22 is a key genetic node that balances the trade-off between immunity and germline health by modulating the functions of different AGOs, thereby shaping the outputs of the RNAi machinery and the dynamics of epigenetic inheritance.

overall_design: Gravid adults were treated with alkaline hypochlorite solution and the embryos were thoroughly washed and incubated in M9 overnight to obtain a synchronized L1 population. Total RNA was isolated from L1 animals using standard phenol-chloroform method using TRIzol or Qiagen RNeasy Kits per manufacture instruction. Libraries for RNA-seq were prepared using NEBNext® Ultra II Directional RNA Library Prep Kit for Illumina® coupled with NEBNext® Poly(A) mRNA Magnetic Isolation Module. The sample quality was accessed on Agilent 2200/4150 BioAnalyzer instrument and High Sensitivity RNA ScreenTapes. The resulting cDNA libraries were pooled and paired-end sequencing was performed on the Nextseq 550/2000 platform. For small RNA-seq, the total RNA was first treated with RNA 5′ Polyphosphatase (epicentre) followed by library preparation using NEBNext® Small RNA Library Prep Set for Illumina®. Size selection on E-gel (Invitrogen, Life Technologies) was performed to enrich for 140-160 nt long cDNA. The sample quality was then accessed on Agilent 2200/4150 BioAnalyzer instrument and High Sensitivity RNA ScreenTapes. The sampled were pooled and sequenced on the Nextseq 550/2000 platform.

first: Chee Kiang

last: Ewe

first: Guy

last: Teichman

first: Maximillian

last: Knott

first: Sarit

last: Anava

first: Mario

last: Bardan Sarmiento

last: Troemel

first: Oded

last: Rechavi


title: Injectable Magnesium-Bisphosphonate MOF-Based Bone Adhesive Prevents Excessive Fibrosis for Osteoporotic Fracture Repair

city: guangzhou

first: Lei

state: guangdong

address: 63 Duobao Road, Liwan District, Guangzhou City, Guangdong Province

institute: The Third Affiliated Hospital of Guangzhou Medical University

summary: Current clinical approaches to promote osteoporotic fracture healing primarily target osteoclast biology, overlooking the negative regulatory role of fibroblasts in fracture healing. Perioperative bisphosphonates (BPs) used in anti-osteoporosis treatment for osteoporotic fractures have become a consensus worldwide. However, excessive fibrosis is induced simultaneously, leading to fracture non-union and atypical femur fractures. It is highly desirable to inhibit osteoclasts but block fibrosis. In this study, an magnesium ions (Mg2+)-BPs MOF-based bone adhesive material was designed to down-regulate SOST and weaken SOST/TGF-β signaling pathway through Mg2+ through transcriptome analysis, thus inhibiting fibrotic differentiation and subsequent disordered mineralization.

overall_design: In this study, a Mg-ALN MOF-based bone adhesive material was designed to antagonize the pathological characteristics of bone fibrosis induced by bisphosphonate (ALN) through Mg2+. Gel, ALN+Gel and Mg-ALN@Gel samples were analyzed by transcriptome sequencing. Mg2+ inhibited fibrotic differentiation by down-regulating SOST and attenuating SOST/TGF-β signaling pathway.

first: Tianhua

last: Xiao

first: Zunlei

last: Gong

first: Dongming

last: Duan

first: Hui

last: Yu

first: Song

last: Liu

first: Yuhe

last: Jiang

first: Xudan

last: Xing

first: Zenghui

last: Wu

first: Le

first: Xuebin B

last: Yang

first: Giuseppe

last: Tronci

first: Chengyun

last: Ning

first: Guoxin

last: Tan


title: Transcriptomic analysis identifies novel cancer associated fibroblast marker in the breast tumour microenvironment

status: Public on May 10 2025

city: Galway

first: Barry

last: Digby

address: University Road

country: Ireland

institute: University of Galway

summary: Cancer associated fibroblasts (CAFs) contribute to tumourigenesis and immune tolerance within the tumour microenvironment (TME). However, the absence of specific molecular markers complicates selective CAF targeting. This study aims to identify novel CAF-specific biomarkers with dual functionality: enhancing anti-tumor immunity and suppressing malignant progression. To address this, we conducted comparative transcriptomic profiling via RNA sequencing of patient-matched CAFs and normal fibroblasts (NFs) isolated from the same breast cancer patient, revealing potential targets with therapeutic relevance.

overall_design: CAFs/NFs were collected from 12 patients with Luminal A (n = 11) and TNBC (n = 1). RNA-seq profiling  of CAFs/NFs was extracted from passage 3 CAFs and NFs.

first: Rui

last: Li

first: Dómhnall

last: O’ Connor

first: Pilib

last: Ó Broin

first: Xiao

last: Hu

first: Ning

last: Ge

first: Paul

middle: G

last: Loftus

first: Vatsal

last: Kumar

first: Eoin

last: McEvoy

first: Stephen

last: Elliman

first: Michael

last: Kerin

first: Laura

last: Barkley


title: The evolutionarily conserved PRP4K-CHMP4B/vps32 splicing circuit regulates autophagy

city: Halifax

first: Graham

last: Dellaire

state: Nova Scotia

address: 5850 College Street

department: Department of Pathology

institute: Dalhousie University

summary: The pre-mRNA processing factor 4 kinase (PRP4K) is an essential gene in animal cells, making interrogation of its function challenging. Here, we report the first knockout model for PRP4K in the social amoeba Dictyostelium discoideum, revealing a new function in splicing events controlling autophagy. When prp4k knockout amoebae underwent multicellular development, we observed defects in differentiation linked to abnormal autophagy and aberrant secretion of stalk cell inducer c-di-GMP. Autophagosome-lysosome fusion was found to be impaired after PRP4K loss in both human cell lines and amoebae. Mechanistically, PRP4K loss results in mis-splicing and reduced expression of the ESCRT-III gene CHMP4B in human cells and its ortholog vps32 in Dictyostelium, and re-expression of CHMP4B or Vps32 cDNA (respectively) restored normal autophagosome-lysosome fusion in PRP4K-deficient cells. Thus, our work reveals a novel PRP4K-CHMP4B/vps32 splicing circuit regulating autophagy that is conserved over at least 600 million years of evolution.

overall_design: cDNA libraries of MCF7 cell line samples expressing control shRNA or shRNA targeting PRP4K expression were generated from one biological replicate.

first: Sabateeshan

last: Mathavarajah

first: Sandhya

last: Chipurupalli

first: Elias

middle: B

last: Habib

first: William

last: Kim

first: Megan

middle: M

last: Aoki

first: Dale

middle: P

last: Corkery

first: Kennedy

middle: I

last: Whelan

first: Jordan

last: Lukacs

first: Melis

last: Erkan

first: Victor

last: Martinez

first: Kevin

last: Smith

last: Montgomery

first: Jayme

last: Salsman

first: Robert

middle: J

last: Huber