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Nat Immunol. 2019 Nov;20(11):1456-1468. doi: 10.1038/s41590-019-0518-7. Epub 2019 Oct 21.

RBPJ-dependent Notch signaling initiates the T cell program in a subset of thymus-seeding progenitors.

Author information

1
Sunnybrook Research Institute, Toronto, Ontario, Canada.
2
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
3
Sunnybrook Research Institute, Toronto, Ontario, Canada. jczp@sri.utoronto.ca.
4
Department of Immunology, University of Toronto, Toronto, Ontario, Canada. jczp@sri.utoronto.ca.

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.

PMID:
31636466
PMCID:
PMC6858571
[Available on 2020-04-21]
DOI:
10.1038/s41590-019-0518-7

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