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Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state [ATAC-seq]

ABSTRACT: Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state [ATAC-seq]

PROVIDER: PRJNA978555 | ENA |

REPOSITORIES: ENA

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Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state [RNA-seq]

Project description:CD4+ T helper 17 (Th17) cells encompass a spectrum of cell states including homeostatic cells that maintain physiological functions such as barrier integrity and pathogenic cells that drive autoimmune tissue inflammation. Identifying the regulators that determine these cell states will provide means to control tissue inflammation without compromising the physiological functions of Th17 cells. Here, we identified TCF1 as the key regulator that determines Th17 cell state. IL-23, a cytokine critical for inducing pathogenic Th17 cells, decreased TCF1 expression. Consistent with this observation, conditional deletion of Tcf7/TCF1 in mature myelin-specific T cells conferred pathogenicity to homeostatic Th17 cells independent of IL-23. Conversely, sustained TCF1 expression impaired acquisition of pathogenicity. Integration of transcriptional and chromatin accessibility data showed that TCF1 maintained homeostatic state through a regulatory network involving ETS family transcription factors, EGR1, and FOXO1 and by binding to and interfering with RORt activity. Our findings provide mechanistic insight into how the homeostatic and pathogenic Th17 cell states are determined and into the association of genetic variants in TCF7 with susceptibility to autoimmunity.

2024-11-03 | GSE233907 | GEO

Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state [ATAC-seq]

2024-11-03 | GSE233905 | GEO

Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state

Project description:Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state

| PRJNA978551 | ENA

Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state [RNA-seq]

Project description:Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state [RNA-seq]

| PRJNA978554 | ENA

Transcription factor TCF1 binds Rorgt and orchestrates a regulatory network that determines homeostatic Th17 cell state

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-11-03 | GSE233908 | GEO

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

Project description:The aim of this study was to analyze the global transcriptional profiles of small intestine (SI) Innate Lymphoid Cells (ILCs) expressing the NK cell marker NKp46. Based on differential expression of the RORgt transcription factor SI NKp46+ ILCs can be divided in NKp46+RORgt- and NKp46+RORgt+ cells. While NKp46+RORgt- cells produce IFN-g, like conventional Natural Killer (NK) cells, NKp46+RORgt+ cells secrete IL-22, like Lymphoid Tissue inducer (LTi) cells. We compared the global transcriptional profiles of both NKp46+RORgt- and NKp46+RORgt+ cells to conventional splenic NK cells and to SI NKp46-RORgt+ cells, which contain adult LTi cells. By following this approach, we showed that SI NKp46+RORγt- ILCs correspond to SI NK cells. We also identified a transcriptional program conserved in adult SI NKp46+RORγt+, NKp46-RORγt+ ILCs and fetal LTi. The various ILC cell populations analyzed in this study were isolated from C57BL/6 RORc(gt)+/GFP reporter mice. SI NKp46+RORγt- (NKp46+GFP-) cells, SI NKp46+RORγt+ cells (NKp46+GFPlow and NKp46+GFPhigh cells) and NKp46-RORγt+ ILCs, including adult LTi cells , were sorted by flow cytometry from CD3- lamina propria cells of small intestine (SI) of RORc(γt)+/GFP reporter mice . Splenic NKp46+RORγt- (NKp46+GFP-) cells were also sorted as the reference for conventional NK cells. Two replicates of each populations were produced and analyzed.

2011-06-20 | E-GEOD-29777 | biostudies-arrayexpress

Gene expression profiling of small intestine (SI) NKp46+RORgt+ and NKp46+RORgt- Innate Lymphoid Cells (ILCs)

2011-06-20 | GSE29777 | GEO

Genome-wide maps of Tcf1 binding locations in splenic CD8 T cells.

Project description:We mapped genome-wide Tcf1 binding locations in mature CD8 T cells to identify its direct target genes. This experiment aims to identify genome-wide binding locations for Tcf1 transcription factor in mature CD8 T cells. The CD8 T cells were isolated from wild-type C57BL/6 mice by negative selection. The chromatin fragments were immunoprecipitated by an anti-Tcf1 antiserum or control rabbit serum (without immunization). The immunoprecipitated fragments were then used in high throughput sequencing. Data processing then revealed >3000 high-confidence Tcf1 binding peaks across the CD8 T cell genome. One important finding is that Tcf1 binds directly to Cd4 gene silencer, and thus explain its important role in suppressing the CD4 coreceptor in mature CD8 T cells.

2014-03-05 | E-GEOD-52070 | biostudies-arrayexpress

CTCF deficiency in CD8 homeostatic proliferation [RNA-seq]

Project description:An intricate interplay among Tcf1/Lef1 and CTCF that orchestrates genomic architecture to coordinately promote CD8+ T cell homeostatic proliferation

2022-04-25 | GSE198264 | GEO

Tcf1-CTCF cooperativity shapes genomic architecture to promote CD8+ T cell homeostasis [Hi-C]

Project description:An intricate interplay among Tcf1/Lef1, CTCF and Stat5 that orchestrates genomic architecture to coordinately promote CD8+ T cell homeostatic proliferation

2022-04-25 | GSE179773 | GEO

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