Multilineage potential and self-renewal define an epithelial progenitor cell population in the adult thymus

Kahlia Y P Wong, Natalie Louise Seach, Marco Barsanti, Joanna Mei Ch'wan Lim, Maree V Hammett, Danika M Khong, Christopher Siatskas, Daniel Herbert Donald Gray, Richard L Boyd, Ann P Chidgey

Research output: Contribution to journalArticleResearchpeer-review

81 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1198 - 1209
Number of pages12
JournalCell Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 2014

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