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

Edward L Y ChenPatrycja K ThompsonJuan-Carlos Zúñiga-Pflücker
Published in: Nature immunology (2019)
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.
Keyphrases
  • bone marrow
  • cell fate
  • induced apoptosis
  • mesenchymal stem cells
  • cell proliferation
  • acute myeloid leukemia
  • quality improvement
  • oxidative stress
  • single cell
  • immune response
  • endoplasmic reticulum stress
  • cell death