A Thymic Epithelial Stem Cell Pool Persists throughout Ontogeny and Is Modulated by TGF-β

Adult tissue-specific stem cells (SCs) mediate tissue homeostasis and regeneration and can give rise to all lineages in the corresponding tissue, similar to the early progenitors that generate organs in the first place. However, the developmental origins of adult SCs are largely unknown. We recently identified thymosphere-forming stem cells (TSFCs) in the adult mouse thymus, which display genuine stemness features and can generate the two major thymic epithelial cell lineages. Here, we show that embryonic TSFCs possess stemness features but differ from adult TSFCs in surface marker profile. Our findings support the model of a continuous thymic SC lineage that is maintained throughout ontogeny. TGF-β signaling differentially affects embryonic versus adult thymosphere formation, suggesting that thymic epithelial SC potency depends on both developmental stage and environmental signals. Collectively, our findings suggest that embryonic TSFCs contribute to an adult SC pool and that TSFC plasticity is controlled by TGF-β signaling. [Display omitted] •Epithelial thymosphere-forming stem cells (TSFCs) are maintained throughout ontogeny•Embryonic TSFCs reside in the FoxN1-negative lineage•Embryonic and adult TSFCs represent a continuous developmental lineage•Embryonic versus adult TSFCs display differential sensitivity to TGF-β signaling Ucar et al. address the developmental origins of adult stem cells by using the thymosphere-forming stem cells (TSFCs) of the thymic epithelium. They provide evidence that TSFCs represent a continuous lineage throughout ontogeny and that the fetal and adult stem cell pool might be differentially regulated by TGF-β.