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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Histone Deacetylase 3 is required for efficient T cell development

ABSTRACT: Hdac3 is an important target of HDAC inhibitors used in the treatment of cutaneous T cell lymphoma. In order to gain an understanding of Hdac3 function in T cells,we deleted Hdac3 from early mouse thymocytes using LCK-Cre. Hdac3 deletion resulted in a loss of single positive thymocytes due to a defect in positive selection at the double positive (DP) stage of thymocyte development. To better characterize this defect, we sorted the DP1 and DP2 populations to for gene expression profiling. Total RNA was extracted from DP1 (GFP+CD4+CD8+CD5loTCRblo) or DP2 (GFP+CD4+CD8+CD5hiTCRbint) thymocytes isolated by FACS from Hdac3+/+ or Hdac3F/F LCK-Cre+ animals. Libraries were constructed from rRNA-depleted total RNA pools to identify altered gene expression in DP populations following Hdac3 deletion.

ORGANISM(S): Mus musculus

SUBMITTER: Scott Hiebert

PROVIDER: E-GEOD-72917 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Histone Deacetylase 3 is required for efficient T cell development

Project description:Hdac3 is an important target of HDAC inhibitors used in the treatment of cutaneous T cell lymphoma. In order to gain an understanding of Hdac3 function in T cells,we deleted Hdac3 from early mouse thymocytes using LCK-Cre. Hdac3 deletion resulted in a loss of single positive thymocytes due to a defect in positive selection at the double positive (DP) stage of thymocyte development. To better characterize this defect, we sorted the DP1 and DP2 populations to for gene expression profiling.

2015-09-11 | GSE72917 | GEO

HDAC3 restrains cytokine signaling during thymocyte development for the generation of CD4 T cells (RNA-Seq)

Project description:CD4 and CD8 T cells are vital components of the immune system. According to the kinetic signaling model, commitment to the CD4 or CD8 lineage is determined by whether persistent TCR signaling or cytokine signaling predominates, respectively. We found histone deacetylase 3 (HDAC3) is critical for the development of CD4 T cells, as its deletion leads to the generation of only CD8SP thymocytes. In the absence of HDAC3, MHC Class II-restricted OT-II thymocytes are redirected to the CD8 cytotoxic lineage. Analysis of histone acetylation and RNA-seq reveals HDAC3-deficient DP thymocytes are biased towards the CD8 lineage prior to positive selection. In addition, HDAC3-deficient DP thymocytes have increased IL-21R expression and STAT5 activation. As a result, HDAC3 is required to restrain cytokine signaling in DP thymocytes and is required for the generation of CD4 T cells.

2019-01-20 | GSE109530 | GEO

HDAC3 restrains cytokine signaling during thymocyte development for the generation of CD4 T cells (ChIP-Seq)

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Gene expression profiling of thymocytes from conditional knock-out mice (FoxN1-Cre mediated KO of Gpr177)

Project description:Comparative gene expression profiling of thymocytes at the DP, CD4 SP and CD8 SP stage derived from FoxN1-Gpr177 mice (FoxN1-Cre mediated deletion of (Exon3 of) Gpr177/Wtls) or C57Bl/6N mice as comparison. Objective was to test the influence of TEC-secreted Wnt ligands on the transcriptome of thymocytes at the respective developmental stages. Total RNA extracted from FACS-sorted primary mouse thymocytes. CD4/8 double positive (DP) thymocytes, CD4 single positive (CD4 SP) thymocytes and CD8 single positive (CD8 SP) thymocytes were FACS-sorted from conditional knock-out mice (FoxN1-Gpr177) and C57Bl/6N mice as comparison.

2015-11-01 | E-GEOD-69766 | biostudies-arrayexpress

Gene Expression of Double Positive LCK:Hdac3 KO 3w old mice

Project description:Analysis of gene expression in double positive (DP) thymoctes from 3w old LCK Hdac3 conditional KO mice. In this data set we sorted GFP double positive (DP) thymocytes from 3w old mice to identify possible signaling and transcripitonal programs that might explain the DP to single positive block in cell maturation

2015-09-29 | GSE73533 | GEO

Cohesin regulates gene expression through spatial clustering of enhancer elements

Project description:H3K27Ac ChIP-seq in wild type and cohesin-deficient thymocytes Rad21 was deleted in CD4+ CD8+ double positive (DP) thymocytes by crossing a Rad21 floxed allele with a Cd4-driven Cre transgene. DP positive thymocytes were FACS-sorted from control and Rad21-/- littermates, which were then used to perform chromatin immunoprecipitation for histone H3 acetylated on lysine 27 (H3K27Ac).

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Genes regulated by HEB and E2A during DP stage of thymocyte development

Project description:To investigate gene targets of the E-proteins HEB and E2A during the CD4+CD8+ double positive (DP) stage of T cell development. We examined E-protein function by simultaneous removal of both HEB (Tcf12) and E2A (Tcfe2a) genes at the DP stage. This was done by crossing mice containing HEB floxed and E2A floxed alleles to a CD4Cre background (Tcf12f/fTcfe2af/fCD4Cre mice). Microarray analysis was used to compare gene expression in HEB and E2A double deficient DP thymocytes (Cre+) to Cre- control DP thymocytes. Keywords: genetic modification

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New role for the (pro)renin receptor in T cell development

Project description:The (pro)renin receptor (PRR) was originally thought to be important in regulating blood pressure via the renin-angiotensin system (RAS), however it is emerging that PRR is instead generally essential for cellular development via its involvement in Wnt signalling. Here, we have specifically deleted PRR from T cells, which require Wnt for their development. T cell-specific PRR-knockout (cKO) mice (ATP6AP2flox/y;Lck-CRE) had a significant decrease in thymic cellularity, corresponding with a 100-fold decrease in the number of CD4+ and CD8+ thymocytes, and a large increase in double negative (DN) precursors. Further characterisation of DN T cell progenitors revealed that deletion of PRR impaired T cell development at multiple stages; including transition from DN3(CD25+CD44-) - DN4(CD25-CD44-), DN4-CD4+ CD8+ double positive (DP), DP-intermediate single positive (CD3-CD8+ ISP) cells. We performed gene expression analysis on sorted DN3 T cells, which indicated that PRR cKO T cells have perturbations in key cellular pathways essential at the DN3 stage, such as RNA processing and translation. Our study identifies a new role for PRR in multiple facets of T cell development, and gives further support to the notion that PRR is generally essential for cellular development.

2015-07-01 | E-MTAB-3568 | biostudies-arrayexpress

Transcription profiling of human fetal thymocytes and circulating naive T cells

Project description:Subpopulations of human fetal thymocyte and circulating naÃ¯ve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naÃ¯ve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naÃ¯ve T cells from adult blood (AB4+).

2007-08-06 | E-GEOD-1460 | biostudies-arrayexpress

Gene Expression Profile during human CD4+ T cell differentiation

Project description:Subpopulations of human fetal thymocyte and circulating naïve T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ naïve T cells from adult blood (AB4+). Keywords = Microarray Keywords = gene expression Keywords = thymocytes Keywords = naïve CD4+ T cell Keywords = recent thymic emigrants Keywords: other

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