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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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https://www.hal.inserm.fr/inserm-03537993
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Submitted on : Thursday, January 20, 2022 - 5:03:57 PM
Last modification on : Friday, January 21, 2022 - 9:39:14 AM
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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, Nature Publishing Group, 2013, 14 (12), pp.1277-1284. ⟨10.1038/ni.2760⟩. ⟨inserm-03537993⟩

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