| First Author | Braunstein M | Year | 2011 |
| Journal | Mol Cell Biol | Volume | 31 |
| Issue | 5 | Pages | 971-82 |
| PubMed ID | 21189289 | Mgi Jnum | J:169181 |
| Mgi Id | MGI:4939982 | Doi | 10.1128/MCB.01034-10 |
| Citation | Braunstein M, et al. (2011) HEB-Deficient T-Cell Precursors Lose T-Cell Potential and Adopt an Alternative Pathway of Differentiation. Mol Cell Biol 31(5):971-82 |
| abstractText | Early thymocytes possess multilineage potential, which is progressively restricted as cells transit through the double-negative stages of T-cell development. DN1 cells retain the ability to become natural killer cells, dendritic cells, B cells, and myeloid cells as well as T cells, but these options are lost by the DN3 stage. The Notch1 signaling pathway is indispensable for initiation of the T-cell lineage and inhibitory for the B-cell lineage, but the regulatory mechanisms by which the T-cell fate is locked in are largely undefined. Previously, we discovered that the E-protein transcription factor HEBAlt promoted T-cell specification. Here, we report that HEB(-/-) T-cell precursors have compromised Notch1 function and lose T-cell potential. Moreover, reconstituting HEB(-/-) precursors with Notch1 activity enforced fidelity to the T-cell fate. However, instead of becoming B cells, HEB(-/-) DN3 cells adopted a DN1-like phenotype and could be induced to differentiate into thymic NK cells. HEB(-/-) DN1-like cells retained GATA3 and Id2 expression but had lower levels of the Bcl11b gene, a Notch target gene. Therefore, our studies have revealed a new set of interactions between HEB, Notch1, and GATA3 that regulate the T-cell fate choice in developing thymocytes. |
