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ThPOK is a critical and multifaceted regulator of myeloid lineage development [Fluidigm]

ABSTRACT: ThPOK is a critical and multifaceted regulator of myeloid lineage development [Fluidigm]

PROVIDER: PRJNA687742 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13304000_1.fastq.gz	Fastqsanger.gz
	SRR13304000_2.fastq.gz	Fastqsanger.gz
	SRR13304001_1.fastq.gz	Fastqsanger.gz
	SRR13304001_2.fastq.gz	Fastqsanger.gz
	SRR13304002_1.fastq.gz	Fastqsanger.gz

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ThPOK is a critical and multifaceted regulator of myeloid lineage development [Fluidigm]

Project description:The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report a novel role for ThPOK as a critical and multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with CITE-Seq, Smart-Seq2, progenitor transfer and clonogenic assays and we show that ThPOK controls monocyte-DC versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered mRNA splicing to reprogram intron retention.

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Project description:ThPOK is a critical and multifaceted regulator of myeloid lineage development

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ThPOK is a critical and multifaceted regulator of myeloid lineage development

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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.

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Essential role of ThPOK autoregulatory loop in maintenance of mature CD4 T cell identity and function [ATAC-seq]

Project description:The transcription factor ThPOK is critical for homeostasis and differentiation of mature T helper cells. Overall goal of this experiment is to show divergent Chromatin pattern of ThPOK-dependent autoregulatory loop disrupted in CD4 T cells compared to WT.

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