Generation of thymus reconstituting T cell progenitors from genetically unmodified human pluripotent stem cells

Derivation of transplantable T cell progenitors from human pluripotent stem cells is the key step towards regenerative therapy of hereditary and acquired immunodeficiencies. Here, we describe an original methodology for differentiation of genetically non-modified human pluripotent stem cells (hPSCs) that yields T cell progenitors capable for direct and unmediated reconstitution of mouse thymus. The hPSC-derived T cell progenitors exhibited a strong thymus and spleen homing potential and developed into single positive human T cells that could enter circulation. Detailed single cell transcriptome analysis confirmed the similarity of hPSC-T cell progenitors with their in vivo counterparts. The transcription profiling attested the emergence of cells that displayed the transcription signature of early T cell progenitors. Invitro differentiation of hPSCs into T cell progenetors