A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development.
Nat Commun
; 7: 11841, 2016 06 17.
Article
em En
| MEDLINE
| ID: mdl-27312418
ABSTRACT
NFATc1 plays a critical role in double-negative thymocyte survival and differentiation. However, the signals that regulate Nfatc1 expression are incompletely characterized. 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 exhibit only P2 promoter-derived Nfatc1ß expression, preTCR-positive thymocytes express both Nfatc1ß and P1 promoter-derived Nfatc1α transcripts. Inducing NFATc1α activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1ß from P2 promoter impairs thymocyte development resulting in severe T-cell lymphopenia. In addition, we show that NFATc1 activity suppresses the B-lineage potential of immature thymocytes, and consolidates their differentiation to T cells. Further, in the pTCR-positive DN3 cells, a threshold level of NFATc1 activity is vital in facilitating T-cell differentiation and to prevent Notch3-induced T-acute lymphoblastic leukaemia. Altogether, our results show NFATc1 activity is crucial in determining the T-cell fate of thymocytes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Fatores de Transcrição NFATC
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Timócitos
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Receptor Notch3
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Linfopenia
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article