GSE116015
Organoid-induced differentiation of conventional T cells from human pluripotent stem cells
Generation of T cells from pluripotent stem cells (PSC) has the potential to transform adoptive immunotherapy for cancer into universal donor, off-the-shelf cellular therapies.  However, differentiation of human PSCs into fully mature T cells has been challenging with existing methods. We report that a 3D organoid method permitted efficient differentiation of human embryonic stem cell and induced pluripotent stem cell-derived mesoderm progenitors to mature, functional conventional T cells with a diverse T cell receptor (TCR) repertoire. This continuous culture system supported both hematopoietic induction and terminal differentiation to naïve, conventional CD3+CD8aß+ and CD3+CD4+ T cells. Introduction of a Class I-restricted TCR in PSCs produced antigen-specific CD8aß+ T cells lacking endogenous TCR expression. Functional assays and RNA sequencing aligned PSC-derived T cells with primary naïve conventional CD8+ T cells. The organoid system presented here provides an effective and scalable platform to generate functional mature T cells from human PSCs. Overall design: Our goal was to analyze and compare transcriptome of human naïve T cells generated in Artificial Thymic Organoids (ATOs) from PSC  with human naïve T cells from thymus and Cord blood ATOs.