title: In vivo fate mapping identifies pre-TCRα expression as an intra- and extrathymic, but not prethymic, marker of T lymphopoiesis.
abstract: Expression of the pre-T cell receptor α (pTα) gene has been exploited in previous studies as a molecular marker to identify tiny cell populations in bone marrow (BM) and blood that were suggested to contain physiologically relevant thymus settling progenitors (TSPs). But to what extent these cells genuinely contribute to thymopoiesis has remained obscure. We have generated a novel pTα(iCre) knockin mouse line and performed lineage-tracing experiments to precisely quantitate the contribution of pTα-expressing progenitors to distinct differentiation pathways and to the genealogy of mature hematopoietic cells under physiological in vivo conditions. Using these mice in combination with fluorescent reporter strains, we observe highly consistent labeling patterns that identify pTα expression as a faithful molecular marker of T lineage commitment. Specifically, the fate of pTα-expressing progenitors was found to include all αβ and most γδ T cells but, in contrast to previous assumptions, to exclude B, NK, and thymic dendritic cells. Although we could detect small numbers of T cell progenitors with a history of pTα expression in BM and blood, our data clearly exclude these populations as physiologically important precursors of thymopoiesis and indicate that they instead belong to a pathway of T cell maturation previously defined as extrathymic.
authors.affiliation: Institute of Immunology, University Clinics Ulm, D-89081 Ulm, Germany.
authors.forename: Hervé
authors.initials: H
authors.lastname: Luche
authors.forename: Tata
authors.initials: T
authors.lastname: Nageswara Rao
authors.forename: Suresh
authors.initials: S
authors.lastname: Kumar
authors.forename: Alpaslan
authors.initials: A
authors.lastname: Tasdogan
authors.forename: Franziska
authors.initials: F
authors.lastname: Beckel
authors.forename: Carmen
authors.initials: C
authors.lastname: Blum
authors.forename: Vera C
authors.initials: VC
authors.lastname: Martins
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Fehling
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D038041:Lymphopoiesis / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology; D060168:Thymocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; C090377:pre-T cell receptor alpha