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HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment

ABSTRACT: HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment

PROVIDER: PRJNA431302 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6504930_1.fastq.gz	Fastqsanger.gz
	SRR6504930_2.fastq.gz	Fastqsanger.gz
	SRR6504940_1.fastq.gz	Fastqsanger.gz
	SRR6504940_2.fastq.gz	Fastqsanger.gz
	SRR6504950_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment

Project description:HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment

| PRJNA431302 | ENA

HDAC3 restrains CD8-lineage genes to maintain a bi-potential state in CD4+CD8+ thymocytes for CD4-lineage commitment.

Project description:CD4 and CD8 T cells are vital components of the immune system. We found that histone deacetylase 3 (HDAC3) is critical for the development of CD4 T cells, as HDAC3-deficient DP thymocytes generate only CD8SP thymocytes in mice. In the absence of HDAC3, MHC Class II-restricted OT-II thymocytes are redirected to the CD8 cytotoxic lineage, which occurs with accelerated kinetics. Analysis of histone acetylation and RNA-seq reveals that HDAC3-deficient DP thymocytes are biased towards the CD8 lineage prior to positive selection. Commitment to the CD4 or CD8 lineage is determined by whether persistent TCR signaling or cytokine signaling predominates, respectively. Despite elevated IL-21R/γc/STAT5 signaling in HDAC3-deficient DP thymocytes, blocking IL-21R does not restore CD4 lineage commitment. Instead, HDAC3 binds directly to CD8-lineage promoting genes. Thus, HDAC3 is required to restrain CD8-lineage genes in DP thymocytes for the generation of CD4 T cells.

| S-EPMC6338460 | biostudies-literature

Gene expression analysis of Ets1-/- CD4+ CD8+ thymocytes

Project description:We performed ChIP-Seq for hallmark TFs (Ets1, Runx1), histone modification marks (H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3), total RNA Pol II, short RNA-Seq as well as nucleosome mapping mainly in murine Rag2 -/- thymocytes. We also performed ChIP-Seq for E47 as well as nucleosome mapping, gene expression microarray analysis in CD4+ CD8+ WT and Ets1-/- DP thymocytes. Overall, we find a key role for the transcription factor Ets1, contributing towards alpha beta T cell lineage commitment via differential transactivation of stage-specific genes orchestrated by dynamic, co-association -mediated chromatin remodeling, as well as transcription dependent generation of a specialized chromatin structure at the TCR beta locus. Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes Gene expression analysis of Ets1-/- CD4+ CD8+ thymocytes

2015-12-19 | E-GEOD-73849 | biostudies-arrayexpress

scRNA-seq of mouse thymocyte CD4 CD8 lineage choice and differentiation

Project description:CD4 and CD8 identify helper and cytotoxic T cell lineages, and serve as co-receptors for MHC-restricted TCR recognition. Despite decades of investigation, questions remain about how TCR specificity and co-receptor gene expression are matched during T cell repertoire selection. Here we address the order and logic of CD4/CD8 lineage choice and differentiation by scRNA-seq. Maturation, activation, and lineage specification emerged as principle components, in this order. Co-receptor gene expression uncovered waves of Cd4+Cd8a+, Cd4+Cd8a- and Cd4-Cd8a+ selection intermediates and revealed gene expression programs associated with each pattern, including TCR- and cytokine signaling genes, lineage markers and transcription factors. While in the unperturbed thymus early Cd4+Cd8a+ selection intermediates were followed first by CD4-like Cd4+Cd8a- and later by CD8-like Cd4-Cd8a+ selection intermediates, the order of co-receptor gene expression was not inherently fixed. These data provide a benchmark for models of CD4/CD8 lineage choice, and a rich resource for interrogating T cell differentiation.

2020-10-25 | GSE149207 | GEO

Mapping of H2A.Z nucleosomes in CD4/CD8 DP thymocytes

Project description:H2A.Z ChIP-Seq in CD4/CD8 DP thymocytes

2017-02-07 | GSE87529 | GEO

Gene expression analysis of CD4+ CD8+ thymocytes [Affymetrix]

Project description:We performed ChIP-Seq for hallmark TFs (Ets1, Runx1), histone modification marks (H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3), total RNA Pol II, short RNA-Seq as well as nucleosome mapping mainly in murine Rag2 -/- thymocytes. We also performed ChIP-Seq for E47 as well as nucleosome mapping, gene expression microarray analysis in CD4+ CD8+ DP thymocytes. Overall, we find a key role for the transcription factor Ets1, contributing towards alpha beta T cell lineage commitment via differential transactivation of stage-specific genes orchestrated by dynamic, co-association -mediated chromatin remodeling, as well as transcription dependent generation of a specialized chromatin structure at the TCR beta locus. Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes Genome-wide analysis via ChIP-Seq for Ets1, Runx1, total RNA Pol II binding, H3K4me1, H3K4me2, H3K4me3, H3K27me3, H3K36me3, short RNA-Seq, Mnase-Seq in murine Rag2 -/- thymocytes, ChIP-Seq for E47, Mnase-Seq and gene expression microarray analysis in DP thymocytes This Series represents gene expression microarray data.

2014-04-01 | E-GEOD-56357 | biostudies-arrayexpress

EZH2 promotes a bi-lineage identity in basal-like breast cancer cells

Project description:The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor-associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a M-bM-^@M-^\bi-lineageM-bM-^@M-^] differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal progenitor gene expression. GATA3 levels increase upon EZH2 silencing, leading to the observed decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition. Total of four treatments (HCC70 cells stably expressing shEZH2, shEED, or EZH2 cDNA, and MDA-MB-468 cells stably expressing shEZH2) were done in duplicates, each with its own control.

2012-09-21 | E-GEOD-36939 | biostudies-arrayexpress

scRNA-seq of mouse thymocyte CD4 CD8 lineage choice and differentiation

Project description:scRNA-seq of mouse thymocyte CD4 CD8 lineage choice and differentiation

| PRJNA627664 | ENA

RNA-seq of CD4 CD8 lineage differentiation in the mouse thymus

Project description:RNA-seq of CD4 CD8 lineage differentiation in the mouse thymus

| PRJNA646978 | ENA

Single-cell multiomic analysis of thymocyte development reveals drivers of CD4+ T cell and CD8+ T cell lineage commitment

Project description:The development of CD4+ T cells and CD8+ T cells in the thymus is critical to adaptive immunity and is widely studied as a model of lineage commitment. Recognition of self-MHCI or MHCII by the T cell antigen receptor (TCR) determines the CD8+ T cell or CD4+ T cell lineage choice, respectively, but how distinct TCR signals drive transcriptional programs of lineage commitment remains largely unknown. Here we applied CITE-seq to measure RNA and surface proteins in thymocytes from wild-type and T cell lineage-restricted mice to generate a comprehensive timeline of cell state for each T cell lineage. These analyses identified a sequential process whereby all thymocytes initiate CD4+ T cell lineage differentiation during an initial wave of TCR signaling, followed by a second TCR signaling wave that coincides with CD8+ T cell lineage specification. CITE-seq and pharmaceutical inhibition experiments implicated a TCR-calcineurin-NFAT-GATA3 axis in driving the CD4+ T cell fate. Our data provide a resource for understanding cell fate decisions and implicate multiple redundant mechanisms in guiding lineage choice.

2023-06-30 | GSE186078 | GEO

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