Dynamic spatio-temporal contribution of single β5t+ cortical epithelial precursors to the thymus medulla

Abstract

Intrathymic T-cell development is critically dependent on cortical and medullary thymic epithelial cells (TECs). Both epithelial subsets originate during early thymus organogenesis from progenitor cells that express the thymoproteasome subunit β5t, a typical feature of cortical TECs. Using in vivo lineage fate mapping, we demonstrate in mice that β5t+ TEC progenitors give rise to the medullary TEC compartment early in life but significantly limit their contribution once the medulla has completely formed. Lineage-tracing studies at single cell resolution demonstrate for young mice that the postnatal medulla is expanded from individual β5t+ cortical progenitors located at the cortico-medullary junction. These results therefore not only define a developmental window during which the expansion of medulla is efficiently enabled by progenitors resident in the thymic cortex, but also reveal the spatio-temporal dynamics that control the growth of the thymic medulla. The thymus medulla is subject to a dramatic expansion during the first weeks of life. Using inducible TEC-specific lineage-tracing, Mayer et al. found that single β5t+ epithelial progenitor cells located at the cortico-medullary junction adopt a medullary TEC fate and actively contribute to this postnatal growth.