title: Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors.
abstract: Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe β5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe β5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult β5t(+) progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal β5t(+) progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny.
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Ohigashi
authors.affiliation: Paediatric Immunology, Department of Biomedicine, University of Basel, Basel 4058, Switzerland; University Children's Hospital Basel, Basel 4058, Switzerland.
authors.forename: Saulius
authors.initials: S
authors.lastname: Zuklys
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Sakata
authors.affiliation: Paediatric Immunology, Department of Biomedicine, University of Basel, Basel 4058, Switzerland; University Children's Hospital Basel, Basel 4058, Switzerland.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Mayer
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hamazaki
authors.affiliation: Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.affiliation: Paediatric Immunology, Department of Biomedicine, University of Basel, Basel 4058, Switzerland; University Children's Hospital Basel, Basel 4058, Switzerland; Developmental Immunology, Department of Paediatrics and Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 8LL, UK.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Hollander
authors.affiliation: Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan. Electronic address: takahama@genome.tokushima-u.ac.jp.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Takahama
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D058948:Cell Tracking; D002478:Cells, Cultured; D004848:Epithelium / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D000066450:Mouse Embryonic Stem Cells / Q000502:physiology; D012038:Regeneration; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology*