| First Author | De Obaldia ME | Year | 2013 |
| Journal | Nat Immunol | Volume | 14 |
| Issue | 12 | Pages | 1277-84 |
| PubMed ID | 24185616 | Mgi Jnum | J:209009 |
| Mgi Id | MGI:5565547 | Doi | 10.1038/ni.2760 |
| Citation | De Obaldia ME, et al. (2013) T cell development requires constraint of the myeloid regulator C/EBP-alpha by the Notch target and transcriptional repressor Hes1. Nat Immunol 14(12):1277-84 |
| abstractText | Notch signaling induces gene expression of the T cell lineage and discourages alternative fate outcomes. Hematopoietic deficiency in the Notch target Hes1 results in severe T cell lineage defects; however, the underlying mechanism is unknown. We found here that Hes1 constrained myeloid gene-expression programs in T cell progenitor cells, as deletion of the myeloid regulator C/EBP-alpha restored the development of T cells from Hes1-deficient progenitor cells. Repression of Cebpa by Hes1 required its DNA-binding and Groucho-recruitment domains. Hes1-deficient multipotent progenitor cells showed a developmental bias toward myeloid cells and dendritic cells after Notch signaling, whereas Hes1-deficient lymphoid progenitor cells required additional cytokine signaling for diversion into the myeloid lineage. Our findings establish the importance of constraining developmental programs of the myeloid lineage early in T cell development. |
