RBPJ-dependent Notch signaling initiates the T cell program in a subset of thymus-seeding progenitors.
Nat Immunol
; 20(11): 1456-1468, 2019 11.
Article
in En
| MEDLINE
| ID: mdl-31636466
ABSTRACT
T cell specification and commitment require Notch signaling. Although the requirement for Notch signaling during intrathymic T cell development is known, it is still unclear whether the onset of T cell priming can occur in a prethymic niche and whether RBPJ-dependent Notch signaling has a role during this event. Here, we established an Rbpj-inducible system that allowed temporal and tissue-specific control of the responsiveness to Notch in all hematopoietic cells. Using this system, we found that Notch signaling was required before the early T cell progenitor stage in the thymus. Lymphoid-primed multipotent progenitors in the bone marrow underwent Notch signaling with Rbpj induction, which inhibited development towards the myeloid lineage in thymus-seeding progenitors. Thus, our results indicated that the onset of T cell differentiation occurred in a prethymic setting, and that Notch played an important role during this event.
Full text:
1
Database:
MEDLINE
Main subject:
Cell Differentiation
/
T-Lymphocyte Subsets
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Immunoglobulin J Recombination Signal Sequence-Binding Protein
/
Receptors, Notch
/
Precursor Cells, T-Lymphoid
Limits:
Animals
Language:
En
Year:
2019
Type:
Article