Generation of mature T cells from human hematopoietic stem/progenitor cells in artificial thymic organoids

Mechanistic studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPC) through to mature naïve T cells. We developed a serum free, artificial thymic organoid (ATO) system that supports highly efficient and reproducible in vitro differentiation and positive selection to generate conventional human T cells from all sources of HSPCs. Deep-sequencing of the TCR variable genes was performed to compare the diversity of the TCR repertoire between ATO-derived CD8SP T cells and naive CD8SP T cells from thymus and blood. Overall design: TCR repertoire analysis of CD3+TCRab+CD8SP T cells derived from cord blood CD34+CD3- HSPCs in ATOs compared with human naïve CD8SP T cells from the thymus and blood