Journal Article Adult Thymic Medullary Epithelium Is Maintained and Regenerated by Lineage-Restricted Cells Rather Than Bipotent Progenitors

Ohigashi, Izumi  ,  Zuklys, Saulius  ,  Sakata, Mie  ,  Mayer, Carlos E.  ,  Hamazaki, Yoko  ,  Minato, Nagahiro  ,  Hollander, Georg A.  ,  Takahama, Yousuke

13 ( 7 )  , pp.1432 - 1443 , 2015-11-17 , Elsevier
Medullary thymic epithelial cells (mTECs) play an essential role in establishing self-tolerance in T cells. mTECs originate from bipotent TEC progenitors that generate both mTECs and cortical TECs (cTECs), although mTEC-restricted progenitors also have been reported. Here, we report in vivo fate-mapping analysis of cells that transcribe β5t, a cTEC trait expressed in bipotent progenitors, during a given period in mice. We show that, in adult mice, most mTECs are derived from progenitors that transcribe β5t during embryogenesis and the neonatal period up to 1 week of age. The contribution of adult β5t+ progenitors was minor even during injury-triggered regeneration. Our results further demonstrate that adult mTEC-restricted progenitors are derived from perinatal β5t+ progenitors. These results indicate that the adult thymic medullary epithelium is maintained and regenerated by mTEC-lineage cells that pass beyond the bipotent stage during early ontogeny.

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