Identification of a Bipotent Epithelial Progenitor Population in the Adult Thymus

•Adult PLET1+ TECs encompass PLET1+UEA1+Ly-51− mTECs and PLET1+Ly-51+UEA1− CMJ TECs•MHCIIhiPLET1+Ly-51+ TECs include bipotent progenitors that can generate mTECs and cTECs•Ly-51+ TECs also contain cTEC-restricted short-term progenitors•Progeny of PLET1+Ly-51+ TECs persist for 9 months in vivo, hinting at TEC stem cells

SummaryThymic 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 IIhi, 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.

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