| First Author | Klein-Hessling S | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11841 | PubMed ID | 27312418 |
| Mgi Jnum | J:239886 | Mgi Id | MGI:5881990 |
| Doi | 10.1038/ncomms11841 | Citation | Klein-Hessling S, et al. (2016) A threshold level of NFATc1 activity facilitates thymocyte differentiation and opposes notch-driven leukaemia development. Nat Commun 7:11841 |
| abstractText | 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 Nfatc1beta expression, preTCR-positive thymocytes express both Nfatc1beta and P1 promoter-derived Nfatc1alpha transcripts. Inducing NFATc1alpha activity from P1 promoter in preTCR-negative thymocytes, in addition to the NFATc1beta 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. |
