title: Deletion of Notch1 converts pro-T cells to dendritic cells and promotes thymic B cells by cell-extrinsic and cell-intrinsic mechanisms.
abstract: Notch1 signaling is required for T cell development and has been implicated in fate decisions in the thymus. We showed that Notch1 deletion in progenitor T cells (pro-T cells) revealed their latent developmental potential toward becoming conventional and plasmacytoid dendritic cells. In addition, Notch1 deletion in pro-T cells resulted in large numbers of thymic B cells, previously explained by T-to-B cell fate conversion. Single-cell genotyping showed, however, that the majority of these thymic B cells arose from Notch1-sufficient cells by a cell-extrinsic pathway. Fate switching nevertheless exists for a subset of thymic B cells originating from Notch1-deleted pro-T cells. Chimeric mice lacking the Notch ligand delta-like 4 (Dll4) in thymus epithelium revealed an essential role for Dll4 in T cell development. Thus, Notch1-Dll4 signaling fortifies T cell commitment by suppressing non-T cell lineage potential in pro-T cells, and normal Notch1-driven T cell development repels excessive B cells in the thymus.
authors.affiliation: Institute for Immunology, University of Ulm, D-89081 Ulm, Germany.
authors.forename: Thorsten B
authors.initials: TB
authors.lastname: Feyerabend
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Terszowski
authors.forename: Annette
authors.initials: A
authors.lastname: Tietz
authors.forename: Carmen
authors.initials: C
authors.lastname: Blum
authors.forename: Hervé
authors.initials: H
authors.lastname: Luche
authors.forename: Achim
authors.initials: A
authors.lastname: Gossler
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gale
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Fehling
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D051881:Receptor, Notch1