title: β-Selection-induced proliferation is required for αβ T cell differentiation.
abstract: Proliferation and differentiation are tightly coordinated to produce an appropriate number of differentiated cells and often exhibit an antagonistic relationship. Developing T cells, which arise in the thymus from a minute number of bone-marrow-derived progenitors, undergo a major expansion upon pre-T cell receptor (TCR) expression. The burst of proliferation coincides with differentiation toward the αβ T cell lineage-but the two processes were previously thought to be independent from one another, although both were driven by signaling from pre-TCR and Notch receptors. Here we report that proliferation at this step was not only absolutely required for differentiation but also that its ectopic activation was sufficient to substantially rescue differentiation in the absence of Notch signaling. Consistently, pharmacological inhibition of the cell cycle machinery also blocked differentiation in vivo. Thus the proliferation step is strictly required prior to differentiation of immature thymocytes.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Taras
authors.initials: T
authors.lastname: Kreslavsky
authors.forename: Michael
authors.initials: M
authors.lastname: Gleimer
authors.forename: Masaki
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Yoon
authors.initials: Y
authors.lastname: Choi
authors.forename: Etienne
authors.initials: E
authors.lastname: Gagnon
authors.forename: Cornelis
authors.initials: C
authors.lastname: Murre
authors.forename: Piotr
authors.initials: P
authors.lastname: Sicinski
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000276:immunology / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D019070:Cell Lineage; D002478:Cells, Cultured; D008213:Lymphocyte Activation; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D051880:Receptors, Notch / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000276:immunology / Q000378:metabolism
chemical_list: D011948:Receptors, Antigen, T-Cell; D051880:Receptors, Notch; D014157:Transcription Factors