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

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.

SUBMITTER: Chen ELY

PROVIDER: S-EPMC6858571 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Chen Edward L Y ELY Thompson Patrycja K PK Zúñiga-Pflücker Juan Carlos JC

Nature immunology 20191021 11

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 tha ...[more]

PMID: 31636466

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