T cell development requires constraint of the myeloid regulator C/EBP-α by the Notch target and transcriptional repressor Hes1.
Nat Immunol
; 14(12): 1277-84, 2013 Dec.
Article
in En
| MEDLINE
| ID: mdl-24185616
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.
Full text:
1
Database:
MEDLINE
Main subject:
T-Lymphocytes
/
Homeodomain Proteins
/
CCAAT-Enhancer-Binding Protein-alpha
/
Basic Helix-Loop-Helix Transcription Factors
/
Receptor, Notch1
Language:
En
Journal:
Nat Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2013
Type:
Article
Affiliation country:
United States