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

T cell specification and commitment requires 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 pre-thymic niche and whether RBPJ-dependent Notch signaling has a role during this event. Here we established an Rbpj-inducible system that allowed the temporal and tissue-specific control of the responsiveness to Notch in all hematopoietic cells. Using this system, we found that Notch signaling was required prior to 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 pre-thymic setting, and that Notch played an important role during this event.