The thymus, the site of T cell generation and maturation, comprises a complex environment containing cells from all three germ layers. Thymic mesenchymal cells play key regulatory roles in the thymus, but their biology is still relatively poorly understood. Now, Nuno Alves and colleagues set out to investigate the developmental origins of thymic fibroblasts, identifying and characterising two subpopulations. They find that, in the foetal thymus, a population designated TFA predominates, whereas at later stages these are largely replaced by TFB cells; the two can be distinguished by levels of expression of the cell surface marker SCA-1. Transcriptomic and cell culture analyses suggest that TFA cells represent a progenitor population that give rise to TFB cells. Moreover, the authors provide evidence for a checkpoint regulating the differentiation of thymic fibroblasts: when thymocyte differentiation is disrupted, the TFB population is severely depleted, suggesting that signals from thymocytes promote fibroblast maturation. These data add to a growing picture in which bidirectional signalling between stromal and thymocyte populations is essential for development, maintenance and function of the thymus.
