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Transcriptional Regulation by NFATc1 during murine thymocyte development

ABSTRACT: Transcriptional Regulation by NFATc1 during murine thymocyte development

PROVIDER: PRJNA813437 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18253331.fastq.gz	Fastqsanger.gz
	SRR18253332.fastq.gz	Fastqsanger.gz
	SRR18253333.fastq.gz	Fastqsanger.gz
	SRR18253344.fastq.gz	Fastqsanger.gz
	SRR18253345.fastq.gz	Fastqsanger.gz

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Transcriptional Regulation by NFATc1 during murine thymocyte development [ChIP-seq]

Project description:In thymus hematopoietic precursor cells differentiate into αβ T cells, γδ T cells, mucosa-associated invariant T cells (MAIT), and natural killer T (NKT) cells. We show that both ablation of NFATc1 or its induction during the DN stages of thymocyte development leads to an almost normal thymocyte development but a marked increase in γδ T cells. The γδ cells deficient for NFATc1 acquire an NKT γδ cell phenotype that exhibits the expression of CD4 co-receptor, the NK1.1 marker, the augmented usage of the Vγ1.1 and Vδ6.3 segments, and an increased in IL4 and IFN-γ production.

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Transcriptional Regulation by NFATc1 during murine thymocyte development [gammadelta_T_cells RNA-seq]

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A threshold level of NFATc1 activity is critical for thymocyte differentiation and to prevent leukemia development

Project description:NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are unknown. Here we show a developmental stage-specific differential expression pattern of Nfatc1 driven by the distal (P1) or proximal (P2) promoters in thymocytes. Whereas, preTCR-negative thymocytes exhibited only P2 promoter-derived Nfatc1b expression, preTCR-positive thymocytes expressed both Nfatc1b and P1 promoter-derived Nfatc1a transcripts. Inducing NFATc1a activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1a from P2 promoter impaired thymocyte development resulting in severe T cell lymphopenia. Additionally, we show that NFATc1 activity suppressed the B-lineage potential of immature thymocytes, and consolidated their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity was vital in facilitating T cell differentiation and to prevent T-acute lymphoblastic leukemia (T-ALL) development. Altogether, our results show NFATc1 activity is crucial in determining the T cell fate of thymocytes.

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Transcriptional Regulation by NFATc1 during murine thymocyte development

Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcriptional Regulation by NFATc1 in CD8+ T cells [RNA-seq]

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Transcriptional Regulation by NFATc1 in CD8+ T cells [ChiP-seq]

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