Redefining epithelial progenitor potential in the developing thymus

Abstract

Cortical and medullary epithelium represent specialised cell types that play key roles in thymocyte development, including positive and negative selection of the T cell repertoire. While recent evidence shows that these epithelial lineages share a common embryonic origin, the phenotype and possible persistence of such progenitor cells in the thymus at later stages of development remain controversial. Through use of a panel of reagents including the putative progenitor marker Mts24, we set out to redefine the stages in the development of thymic epithelium. In the early embryonic day (E)12 thymus anlagen we find that almost all epithelial cells are uniformly positive for Mts24 expression. In addition, while the thymus at later stages of development was found to contain distinct Mts24(+) and Mts24(-) epithelial subsets, thymus grafting experiments show that both Mts24(+) and Mts24(-) epithelial subsets share the ability to form organised cortical and medullary thymic microenvironments that support T cell development, a function shown previously to be lost in the Mts24(-) cells by E15 when lower cell doses were used. Our data help to clarify stages in thymic epithelial development and provide important information in relation to currently used markers of epithelial progenitors.