Thymic epithelial organoids mediate T cell development

Although the advent of organoids opened unprecedented perspectives for basic and translational research, immune system-related organoids remain largely underdeveloped. Here we established organoids from the thymus, the lymphoid organ responsible for T cell development. We identified conditions enabling thymic epithelial progenitor cell proliferation and development into organoids with in vivo-like transcriptional profiles and diverse cell populations. Contrary to two-dimensional cultures, thymic epithelial organoids maintained thymus functionality in vitro and mediated physiological T cell development upon reaggregation with T cell progenitors. The reaggregates showed in vivo-like epithelial diversity and ability to attract T cell progenitors. Thymic epithelial organoids provide new opportunities to study TEC biology and T cell development in vitro, pave the way for future thymic regeneration strategies and are the first organoids originating from the stromal compartment of a lymphoid organ. Summary statement Establishment of organoids from the epithelial cells of the thymus which resemble their in vivo counterpart and have thymopoietic ability in reaggregate culture.