title: Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus.
abstract: Thymic epithelial cells (TECs) are critically required for T cell development, but the cellular mechanisms that maintain adult TECs are poorly understood. Here, we show that a previously unidentified subpopulation, EpCam(+)UEA1(-)Ly-51(+)PLET1(+)MHC class II(hi), which comprises <0.5% of adult TECs, contains bipotent TEC progenitors that can efficiently generate both cortical (c) TECs and medullary (m) TECs. No other adult TEC population tested in this study contains this activity. We demonstrate persistence of PLET1(+)Ly-51(+) TEC-derived cells for 9 months in vivo, suggesting the presence of thymic epithelial stem cells. Additionally, we identify cTEC-restricted short-term progenitor activity but fail to detect high efficiency mTEC-restricted progenitors in the adult thymus. Our data provide a phenotypically defined adult thymic epithelial progenitor/stem cell that is able to generate both cTECs and mTECs, opening avenues for improving thymus function in patients.
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ulyanchenko
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Kathy E
authors.initials: KE
authors.lastname: O'Neill
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Tanya
authors.initials: T
authors.lastname: Medley
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Farley
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Harsh J
authors.initials: HJ
authors.lastname: Vaidya
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Alistair M
authors.initials: AM
authors.lastname: Cook
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK.
authors.forename: Natalie F
authors.initials: NF
authors.lastname: Blair
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, 5, Little France Drive, Edinburgh EH16 4UU, UK. Electronic address: c.blackburn@ed.ac.uk.
authors.forename: C Clare
authors.initials: CC
authors.lastname: Blackburn
mesh_terms: D000818:Animals; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010641:Phenotype; D011257:Pregnancy Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology*; D059467:Transcriptome
chemical_list: C526395:Plet-1 protein, mouse; D011257:Pregnancy Proteins