Ly6d expression delineates two putative postnatal thymus epithelial progenitor cells that are differentially affected by aging.

To date, the identity and maintenance of postnatal thymic epithelial progenitor cells (TEPCs) remain unclear, as does the persistence of bipotent TEPCs after birth or whether lineage-restricted progenitors independently maintain separate TEC compartments. Using an inducible lineage-tracing system based on expression of the thymoproteasomal protein β5t, which is expressed in embryonic and a subset of postnatal TEPCs, we explored the early dynamics of the relationships between thymic epithelial cell (TEC) progenitors and their progeny. Our results identified two potential lineage-biased progenitor subpopulations, distinguished by Ly6d expression. Additionally, we observed that aging disproportionately affects Ly6d- compared to Ly6d+ TEPCs, with implications for rejuvenation of aging thymic epithelia. This study provides insights into the developmental pathways of TEC lineages and their maintenance, contributing to strategies for enhancing thymic function in aging and disease.