title: Notch-dependent T-lineage commitment occurs at extrathymic sites following bone marrow transplantation.
abstract: Early T-lineage progenitors (ETPs) arise after colonization of the thymus by multipotent bone marrow progenitors. ETPs likely serve as physiologic progenitors of T-cell development in adult mice, although alternative T-cell differentiation pathways may exist. While we were investigating mechanisms of T-cell reconstitution after bone marrow transplantation (BMT), we found that efficient donor-derived thymopoiesis occurred before the pool of ETPs had been replenished. Simultaneously, T lineage-restricted progenitors were generated at extrathymic sites, both in the spleen and in peripheral lymph nodes, but not in the bone marrow or liver. The generation of these T lineage-committed cells occurred through a Notch-dependent differentiation process. Multipotent bone marrow progenitors efficiently gave rise to extrathymic T lineage-committed cells, whereas common lymphoid progenitors did not. Our data show plasticity of T-lineage commitment sites in the post-BMT environment and indicate that Notch-driven extrathymic Tlineage commitment from multipotent progenitors may contribute to early T-lineage reconstitution after BMT.
authors.affiliation: 611 BRB II/III, 421 Curie Blvd, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Maillard
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Schwarz
authors.forename: Arivazhagan
authors.initials: A
authors.lastname: Sambandam
authors.forename: Terry
authors.initials: T
authors.lastname: Fang
authors.forename: Olga
authors.initials: O
authors.lastname: Shestova
authors.forename: Lanwei
authors.initials: L
authors.lastname: Xu
authors.forename: Avinash
authors.initials: A
authors.lastname: Bhandoola
authors.forename: Warren S
authors.initials: WS
authors.lastname: Pear
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D051880:Receptors, Notch