Project description: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 diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. Contrary to these 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 are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries.
Project description: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 diverse cell populations and transcriptional profiles resembling in vivo thymic epithelial cells (TECs) more closely than traditional TEC cultures. Contrary to these 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 are the first organoids originating from the stromal compartment of a lymphoid organ. They provide new opportunities to study TEC biology and T cell development in vitro, paving the way for future thymic regeneration strategies in ageing or acute injuries.
Project description:Here, we used single-cell RNA-sequencing (scRNA-seq) to profile intestinal epithelial only organoids (also known as enteroids) from human fetal duodenum after one passage of in vitro growth. Organoids were grown in the standard 25% LWRN media with either 100 ng/ml of epidermal growth factor (EGF) or 1 ng/ml of EPIREGULIN (EREG) added.
Project description:Mouse thymic epithelial cell organoids, cultured in (1) expansion medium, (2) differentiation medium, or (3) differentiation medium with Rank ligand and retinoic acid (DM+RR), were FACS sorted into plates to follow the SORT-seq protocol (Muraro et al., 2016).
Project description:We profiled medullary thymic epithelial cell subsets from a variety of conditions by scRNA-seq to investigate mechanisms of T-cell tolerance.