Multilineage Potential and Self-Renewal Define an Epithelial Progenitor Cell Population in the Adult Thymus
Kahlia Wong,
Natalie L. Lister,
Marco Barsanti,
Joanna M.C. Lim,
Maree V. Hammett,
Danika M. Khong,
Christopher Siatskas,
Daniel H.D. Gray,
Richard L. Boyd,
Ann P. Chidgey
Affiliations
Kahlia Wong
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Natalie L. Lister
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Marco Barsanti
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Joanna M.C. Lim
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Maree V. Hammett
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Danika M. Khong
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Christopher Siatskas
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Daniel H.D. Gray
Molecular Genetics of Cancer Division and Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC 3052, Australia
Richard L. Boyd
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
Ann P. Chidgey
Stem Cells and Immune Regeneration Laboratory, Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, VIC 3800, Australia
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.
