T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1 - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Nature Immunology Year : 2013

T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1

Abstract

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-α 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.
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inserm-03537993 , version 1 (20-01-2022)

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Maria Elena de Obaldia, J Jeremiah Bell, Xinxin Wang, Christelle Harly, Yumi Yashiro-Ohtani, et al.. T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1. Nature Immunology, 2013, 14 (12), pp.1277-1284. ⟨10.1038/ni.2760⟩. ⟨inserm-03537993⟩

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