title: Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus.
abstract: Thymic epithelial cells (TECs) are critical for T cell development and self-tolerance but are gradually lost with age. The existence of thymic epithelial progenitors (TEPCs) in the postnatal thymus has been inferred, but their identity has remained enigmatic. Here, we assessed the entire adult TEC compartment in order to reveal progenitor capacity is retained exclusively within a subset of immature thymic epithelium displaying several hallmark features of stem/progenitor function. These adult TEPCs generate mature cortical and medullary lineages in a stepwise fashion, including Aire+ TEC, within fetal thymus reaggregate grafts. Although relatively quiescent in vivo, adult TEPCs demonstrate significant in vitro colony formation and self-renewal. Importantly, 3D-cultured TEPCs retain their capacity to differentiate into cortical and medullary TEC lineages when returned to an in vivo thymic microenvironment. No other postnatal TEC subset exhibits this combination of properties. The characterization of adult TEPC will enable progress in understanding TEC biology in aging and regeneration.
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Kahlia
authors.initials: K
authors.lastname: Wong
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Lister
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Marco
authors.initials: M
authors.lastname: Barsanti
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Joanna M C
authors.initials: JM
authors.lastname: Lim
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Maree V
authors.initials: MV
authors.lastname: Hammett
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia; Harvard Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Boston, MA 02138, USA.
authors.forename: Danika M
authors.initials: DM
authors.lastname: Khong
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Siatskas
authors.affiliation: Molecular Genetics of Cancer Division and Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia.
authors.forename: Daniel H D
authors.initials: DH
authors.lastname: Gray
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Boyd
authors.affiliation: Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia. Electronic address: ann.chidgey@monash.edu.
authors.forename: Ann P
authors.initials: AP
authors.lastname: Chidgey
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013950:Thymus Gland / Q000166:cytology*