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Mus musculus

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

PROVIDER: PRJNA318023 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3356107.fastq.gz	Fastqsanger.gz
	SRR3356108.fastq.gz	Fastqsanger.gz

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Similar Datasets

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.

2016-04-20 | GSE80138 | GEO

Transcriptional Regulation by NFATc1 during murine thymocyte development

Project description:Transcriptional Regulation by NFATc1 during murine thymocyte development

| PRJNA813437 | ENA

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

2023-02-28 | GSE198030 | GEO

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

2023-02-28 | GSE198028 | GEO

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

2023-02-28 | GSE198029 | GEO

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

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

| PRJNA813442 | ENA

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

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

| PRJNA813440 | ENA

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

Project description:Transcriptional Regulation by NFATc1 during murine thymocyte development [BirA RNA-seq]

| PRJNA813441 | ENA

SMAD4-NFATc1 protein-protein interaction informed therapeutic vulnerability in SMAD4-deficient pancreatic cancer

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by a median survival rate of approximately six months. While genetic profiling has uncovered common mutations in PDAC, developing targeted therapeutic strategies remains challenging. SMAD4 is frequently mutated or deleted in 30-55% of PDAC patients and correlates with poor survival rates. Such mutations frequently result in loss-of-function, thereby disrupting normal cell cycle regulation and contributing to tumorigenesis. Therefore, translating SMAD4 genotype into actionable targets are highly desired for therapeutic innovation in PDAC. In this study, we performed a SMAD4-focused oncogenic protein-protein interaction (oncoPPI) network mapping and revealed a direct physical interaction between SMAD4 and NFATc1. We found that SMAD4 interacts with NFATc1 in a TGF-independent and NFATc1 phosphorylation-dependent manner. Further, SMAD4 sequesters NFATc1 in cytoplasm and inhibits NFATc1 transcriptional activity. In PDAC cells, SMAD4-loss releases its inhibitory activity on NFATc1, activates NFATc1 transcriptional activity which drives STAT3 mRNA and protein upregulation. Pharmacological profiling identified multiple STAT3 inhibitors selectively inhibit the growth of SMAD4-loss PDAC cells. These results suggested a rewired SMAD4-NFATc1-STAT3 axis and targeting STAT3 as a potential therapeutic strategy in SMAD4-loss PDAC.

2026-02-02 | PXD067749 | Pride

Myocardial Differentiation is Dependent upon Endocardial Signalling During Early Cardiogenesis in vitro

Project description:The endocardium interacts with the myocardium to promote proliferation and morphogenesis during the later stages of heart development. However, the role of the endocardium in early cardiac ontogeny remains under-explored. Given the shared origin, subsequent juxtaposition, and essential cell-cell interactions of endocardial and myocardial cells throughout heart development, we hypothesized that paracrine signaling from the endocardium to the myocardium is critical for initiating early differentiation of myocardial cells. To test this, we generated an in vitro, endocardial-specific ablation model using the diphtheria toxin receptor under the regulatory elements of the NFATc1 genomic locus (NFATc1-DTR) Early treatment of NFATc1-DTR embryoid bodies with diphtheria toxin efficiently ablated endocardial cells, which significantly attenuated the percent of beating EBs in culture and expression of early and late myocardial differentiation markers. The addition of Bmp2 during endocardial ablation partially rescued myocyte differentiation, maturation and function. Therefore, we conclude that early stages of myocardial differentiation rely on endocardial paracrine signaling mediated in part by Bmp2. Our findings provide novel insight into early endocardial-myocardial interactions that can be explored to promote early myocardial development and growth.

2019-05-01 | GSE119505 | GEO

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