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SMART-Seq analysis to understand the differences between WT and SRC-3-/- Tregs transcriptome

ABSTRACT: SMART-seq analysis is used for single cells or for a small amount of purified total RNA from low number of cells. The goal of this study to compare the quantitative differences between the SRC-3+ and SRC-3-/- Tregs cell transcriptomes. Method: Tregs were isolated from FOXP3cre SRC-3f/f (SRC-3KO) and FOXP3 cre monogenic (WT) mice and sorted for GFP expression and the expression of cre

ORGANISM(S): Mus musculus

PROVIDER: GSE199085 | GEO | 2025/03/19

REPOSITORIES: GEO

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SMART-Seq analysis to understand the differences between WT and SRC-3-/- Tregs transcriptome

Project description:SMART-Seq analysis to understand the differences between WT and SRC-3-/- Tregs transcriptome

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Project description:This SuperSeries is composed of the SubSeries listed below. To determine the molecular regulation of Tregs by Setd2, Spleen or large intestine Tregs (CD3+CD4+Foxp3-YFP+) were purified from littermate Foxp3Cre-YFPSetd2f/+ and Foxp3Cre-YFPSetd2f/f mice. Setd2-deficient and control Tregs were subjected to RNA-seq, RNA Polymerase II CUT&Tag or H3K27ac CUT&Tag analyses.

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Critical Requirement of the DNA Methyltransferase, Dnmt1, for the Development and Function of Foxp3+ Regulatory T Cells

Project description:We investigated the role of DNMT1 in immune homeostasis by generating mice lacking DNMT1 in Foxp3+ T-regulatory (Treg) cells. These mice showed decreased peripheral Foxp3+ Tregs, complete loss of Foxp3+ Treg suppressive functions in vitro and in vivo, and died from autoimmunity by 3-4 weeks unless they received perinatal transfer of wild-type Tregs that prolonged their survival. Methylation of CpG-sites in the TSDR region of Foxp3 was unaffected by DNMT1 deletion, but microarray revealed more >500 proinflammatory and other genes were upregulated in DNMT1-/- Tregs. CD4-Cre-mediated DNMT1 deletion showed inability of conventional T cells to convert to Foxp3+ Treg under appropriate polarizing conditions. Hence, DNMT1 is absolutely necessary for maintenance of the gene program required for normal Treg development and function. RNA from three independent samples of magnetically separated CD4+CD25+ Treg of fl-DNMT1/Foxp3cre mice, compared to wild type (C57BL6) control

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Project description:Foxp3+ T-regulatory (Treg) cells maintain immune homeostasis and limit autoimmunity, but can also curtail host responses to cancers. Tregs are therefore promising targets to enhance anti-tumor immunity. Histone/protein acetyltransferases (HATs) promote chromatin accessibility, gene transcription and the function of multiple transcription factors and non-histone proteins. We found that conditional deletion or pharmacologic inhibition of one specific HAT, p300, in Foxp3+ Tregs, increased TCR-induced apoptosis in Tregs, impaired Treg suppressive function and iTreg peripheral conversion, and limited tumor growth in immunocompetent, but not in immunodeficient, hosts. Our data demonstrate that p300 is important for Foxp3+ Treg function and homeostasis in vivo and in vitro, and identify a novel mechanism to diminish Treg function without overtly impairing effector Tcell responses or inducing autoimmunity. Collectively, these data suggest a new approach for cancer immunotherapy. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice, compared to wild type (Foxp3cre) control (all C57Bl/6 background).

2013-08-18 | E-GEOD-47989 | biostudies-arrayexpress

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2023-11-20 | GSE122913 | GEO

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Src

Project description:Rattus norvegicus Src, SRC proto-oncogene, non-receptor tyrosine kinase [Source:RGD Symbol;Acc:620795], is differentially expressed in 26 experiment(s);

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