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Gene Expression in Effector T cells, wildtype of Thpok-deficient

ABSTRACT: The transcription factor Thpok is essential for CD4 T cell development in the thymus and remains expressed in post-thymic CD4 T cells. We post-thymically inactivated Thpok and compared microarray gene expression in Thpok-deficient CD4 T cells to that in their wildtype CD4 or CD8 counterparts We show that Thpok constrains the transcriptional circuitry to maintain CD4+-lineage integrity in naïve cells and to couple effector differentiation to environmental cues after antigenic stimulation. Redundantly with the related factor LRF, Thpok is continuously needed to prevent the trans-differentiation of mature CD4+ into -CD8+ T cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE57846 | GEO | 2014/08/15

SECONDARY ACCESSION(S): PRJNA248219

REPOSITORIES: GEO

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Gene Expression in Effector T cells, wildtype of Thpok-deficient

Project description:The transcription factor Thpok is essential for CD4 T cell development in the thymus and remains expressed in post-thymic CD4 T cells. We post-thymically inactivated Thpok and compared microarray gene expression in Thpok-deficient CD4 T cells to that in their wildtype CD4 or CD8 counterparts We show that Thpok constrains the transcriptional circuitry to maintain CD4+-lineage integrity in naM-CM-/ve cells and to couple effector differentiation to environmental cues after antigenic stimulation. Redundantly with the related factor LRF, Thpok is continuously needed to prevent the trans-differentiation of mature CD4+ into -CD8+ T cells. We activated naM-CM-/ve CD4 T cells (either wild-type or Thpok-deficient) and CD8 T cells (wild-type) in vitro under Th1 conditions. Differentiated effectors were sorted 4 days after activation into CD4+CD8- and CD4-CD8+ (wild-type) and CD4+CD8- and CD4+CD8+ (Thpok-deficient) subsets. Total RNA was extracted from sorted subsets and processed for microarray analyses (Affymetrix Mouse Exon 1.0 ST array) at the NCI microarray facility, following the manufacturerM-bM-^@M-^Ys recommendation. Data is from 3 replicates (except wild-type CD4-CD8+ cells, for which two samples only were processed), generated from two distinct cell preparations.

2014-08-15 | E-GEOD-57846 | biostudies-arrayexpress

RNASeq comparing Thpok and LRF-deficient Tregs to Control

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Gene expression in MHCII restricted mature thymocytes from Thpok-RKF- or Thpok-RKF+ Thpokfl/flRunx3fl/dYFPCd4-Cre+ mixed Bone marrow chimera.

Project description:Thpok-RKF which harbors a mutation in the BTB domain and disrupts the interaction between NuRD complex could not repress CD8 and CD8 lineage genes expression in Thpokfl/flRunx3fl/dYFPCd4-Cre+ from B2m-/- host. However, Thpok-RKF upregulates CD4 expression in these mice.

2022-06-10 | GSE185217 | GEO

NuRD complex recruitment to Thpok mediates CD4+ T cell lineage differentiation

Project description:Although BTB-zinc finger (BTB-ZF) transcription factors control the differentiation of multiple hematopoietic and immune lineages, how they function is poorly understood. The BTB-ZF factor Thpok controls intrathymic CD4+ T cell development and expression of most CD4+- and CD8+-lineage genes. Here, we identify the nucleosome remodeling and deacetylase (NuRD) complex as a novel Thpok cofactor. We locate three amino-acid residues within the Thpok BTB domain that are required for both NuRD binding and Thpok functions, and show that NuRD recruitment recapitulates the functions of the Thpok BTB domain. NuRD mediates Thpok repression of CD8+-lineage genes, including the transcription factor Runx3, but is dispensable for Cd4 expression. We show that these functions cannot be performed by the BTB domain of the Thpok-related factor Bcl6, which fails to bind NuRD. Thus, cofactor binding critically contributes to the functional specificity of BTB-zinc finger factors, which control the differentiation of most hematopoietic subsets.

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Transcriptional Reprogramming of Mature CD4 T helper Cells generates distinct MHC class II restricted Cytotoxic T Lymphocytes

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2012-12-10 | E-GEOD-42277 | biostudies-arrayexpress

An Integrated Epigenomic and Transcriptomic Map of Mouse and Human ab T Cell Development (Thpok ChIPSeq)

Project description:ab lineage T cells, most of which are CD4+ or CD8+ and recognize MHC I or MHC II-presented antigens, are essential for immune responses and develop from CD4+CD8+ thymocytes. The absence of in vitro models and the heterogeneity of ab thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human ab thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4+ and CD8+ lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. Through computational analysis of single-cell data and binding sites for the CD4+ lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4+ or CD8+ lineage differentiation, and with expression of Thpok or of the CD8+ lineage factor Runx3. Our findings provide insight into the mechanisms of CD4+ and CD8+ T cell differentiation and a foundation for mechanistic investigations of ab T cell development.

2020-11-25 | GSE148976 | GEO

Thpok genome-wide occupancy in CD4+ T cells

Project description:Genome-wide occupancy of the transcription factor Thpok in activated CD4+ T cells

2019-01-08 | GSE116506 | GEO

Transcriptional changes in intraepithelial CD4 lymphocytes

Project description:We investigated transcriptional changes in CD4CD8aa and CD4 intraepthelial lymphocytes. TCRÎ±Î² thymocytes differentiate to either CD8Î±Î² cytotoxic T lymphocytes or CD4 T helper cells. This functional dichotomy is controlled by key transcription factors, including the T helper master regulator, ThPOK, which suppresses the cytolytic-program in MHC class II restricted CD4 thymocytes. ThPOK continues to repress CD8-lineage genes in mature CD4 T cells, even as they differentiate to T helper effector subsets. Surprisingly, we show here that the T helper-fate is not fixed and that mature antigen-stimulated CD4 T cells can switch off Thpok expression and reactivate CD8-lineage genes. This unexpected plasticity results in the post-thymic termination of the T helper program and the functional differentiation of distinct MHC class II restricted CD4 cytotoxic T lymphocytes. Intraepithelial_CD4_CD8a neg vs CD8a pos. Two sample set of CD4CD8aa and CD4 intraepthelial lymphocytes (IEL) from small intestine of RAG knockout mice ( 8 weeks after transfer of naive CD4 cells, adoptive tranfer model of colitis), were prepared via cell sorting, and RNA was prepared by TRIZol (Invitrogen, USA) . Data were analyzed in GeneSpring GX10. For microarray analysis, RNA was labeled and hybridized to GeneChip Mouse Genome 430 2.0 arrays according to the Affymetrix protocols. Data were analyzed in GeneSpring GX10.

2013-01-08 | E-GEOD-41257 | biostudies-arrayexpress

Gene expression profiling from memory P14 T cells with control or mutated ThPOK

Project description:We noticed that ThPOK repression is readily abrogated upon in vitro TCR stimulation of peripheral CD8 T cells. This observation prompted us to investigate a role of ThPOK in the CD8 T cell response to an acute viral infection. We observed that clonal expansion is significantly less in both primary and secondary CD8 T cell responses in the absence of functional ThPOK. To approach this mechanism, we carried out a microarray analysis for comparison of gene expression between ThPOKhd/hd and ThPOKwt/wt P14 memory T cells.

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The NuRD complex is required for Thpok-mediated CD4+ T cell development

Project description:This data represent characterization of the interactome of murine Thpok. A version of Thpok (Thpok-Bio) subject to biotinylation in vivo by the BirA biotin ligase was used; to assess Thpok interactions in primary cells, Thpok-Bio was retrovirally expressed in in vitro activated CD4+ T cells from Thpokfl/fl Ox40-Cre+ mice carrying a Rosa26BirA allele. Expression of Ox40-Cre, initiated upon T cell activation, causes the deletion of endogenous Thpokfl alleles, so that transduced cells only express Thpok-Bio. Two Thpok deletion constructs (BKK and RFK) were also analyzed. Following streptavidin pulldown, proteins were separated by SDS-PAGE, the full lane cut into 9 slices, and in-gel digested. FIles are: 1384 - empty vector; 1385 - Thpok; 1386 - Thpok + Ethidium Bromide; 1387 - Thpok BKK; 1388 - Thpok RFK.

| MSV000088126 | MassIVE

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