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 nave, conventional CD3+CD8+ and CD3+CD4+ T cells. Introduction of a Class I-restricted TCR in PSCs produced antigen-specific CD8+ T cells lacking endogenous TCR expression. Functional assays and RNA sequencing aligned PSC-derived T cells with primary nave conventional CD8+ T cells. The organoid system presented here provides an effective and scalable platform to generate functional mature T cells from human PSCs. SOURCE: Gay,Miriam,Crooks (gcrooks@mednet.ucla.edu) -  University of California Los Angeles

Pluto Bioinformatics

GSE116015: Organoid-induced differentiation of conventional T cells from human pluripotent stem cells