title: A dynamic niche provides Kit ligand in a stage-specific manner to the earliest thymocyte progenitors.
abstract: Thymic T cell development is initiated from bone-marrow-derived multi potent thymus-seeding progenitors. During the early stages of thymocyte differentiation, progenitors become T cell restricted. However, the cellular environments supporting these critical initial stages of T cell development within the thymic cortex are not known. Here we use the dependence of early, c-Kit-expressing thymic progenitors on Kit ligand (KitL) to show that CD4(-)CD8(-)c-Kit(+)CD25(-) DN1-stage progenitors associate with, and depend on, the membrane-bound form of KitL (mKitL) provided by a cortex-specific KitL-expressing vascular endothelial cell (VEC) population. In contrast, the subsequent CD4(-)CD8(-)c-Kit(+)CD25(+) DN2-stage progenitors associate selectively with cortical thymic epithelial cells (cTECs) and depend on cTEC-presented mKitL. These results show that the dynamic process of early thymic progenitor differentiation is paralleled by migration-dependent change to the supporting niche, and identify VECs as a thymic niche cell, with mKitL as a critical ligand.
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Mario
authors.initials: M
authors.lastname: Buono
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.|Haematopoietic Stem Cell Biology Laboratory, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Facchini
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.|Haematopoietic Stem Cell Biology Laboratory, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Sahoko
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Supat
authors.initials: S
authors.lastname: Thongjuea
authors.affiliation: Wolfson Imaging Center, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Dominique
authors.initials: D
authors.lastname: Waithe
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.|Haematopoietic Stem Cell Biology Laboratory, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Tiago C
authors.initials: TC
authors.lastname: Luis
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.|Haematopoietic Stem Cell Biology Laboratory, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Alice
authors.initials: A
authors.lastname: Giustacchini
authors.affiliation: Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Besmer
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.|Haematopoietic Stem Cell Biology Laboratory, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Mead
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.|Haematopoietic Stem Cell Biology Laboratory, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Sten Eirik W
authors.initials: SE
authors.lastname: Jacobsen
authors.affiliation: MRC Molecular Hematology Unit, University of Oxford, Oxford OX3 9DS, UK.
authors.forename: Claus
authors.initials: C
authors.lastname: Nerlov
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000378:metabolism*; D019899:Paracrine Communication / Q000235:genetics; D010641:Phenotype; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D055153:Stem Cell Niche; D060168:Thymocytes / Q000378:metabolism*
chemical_list: D019089:Stem Cell Factor