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

• Published in: Nature immunology Vol. 20; no. 11; pp. 1456 - 1468
• Main Authors: Chen, Edward L. Y., Thompson, Patrycja K., Zúñiga-Pflücker, Juan Carlos
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2019; Nature Publishing Group
• Subjects: 631/250/1619/554; 631/250/232/2058; Analysis; Animals; Biomedical and Life Sciences; Biomedicine; Bone marrow; Cell differentiation; Cell Differentiation - immunology; Cell Lineage - immunology; Cell Separation; Cellular signal transduction; Female; Flow Cytometry; Frogs; Hemopoiesis; Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics; Immunoglobulin J Recombination Signal Sequence-Binding Protein - metabolism; Immunology; Infectious Diseases; Lymphocytes; Lymphocytes T; Male; Mice; Mice, Transgenic; Osteoprogenitor cells; Physiological aspects; Precursor Cells, T-Lymphoid - physiology; Primary Cell Culture; Receptors, Notch - metabolism; Signal Transduction - immunology; T cells; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Thymus; Thymus gland; Thymus Gland - cytology; Thymus Gland - immunology; Canada
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/s41590-019-0518-7

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. Zúñiga-Pflücker and colleagues show that Notch signaling is required before the thymic stages of T cell development to inhibit the myeloid lineage potential in thymus-seeding progenitors.