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A comprehensive library of human transcription factors for cell fate engineering

ABSTRACT: A comprehensive library of human transcription factors for cell fate engineering

PROVIDER: PRJNA670483 | ENA |

REPOSITORIES: ENA

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Project description:Human pluripotent stem cell (hPSC)-derived cells offer an unprecedented opportunity to model diverse human tissue functions. However, the field lacks a generalized approach to rapidly and efficiently generate individual cell types of interest and to incorporate them into complex but defined tissues. To systematically explore the transcription factor (TF)-mediated hPSC programming landscape, we constructed the Human TFome: a comprehensive human TF library containing 1,564 TF (1,732 splice-isoforms). We discovered 241 previously unreported factors that individually converted hPSCs into diverse lineages with up to 99% efficiency in four days without alteration of external factors. Among these, we programmed neurons, fibroblasts, oligodendrocytes and endothelial cells that have molecular, transcriptomic and functional similarity to primary cells. Splice-isoform-specificity doubled endothelial conversion efficiency into in vivo-functional cells. Our cell-autonomous approach enabled parallel and orthogonal hPSCs programming into multiple cell types simultaneously without altering any microenvironmental cues. We generated in vivo-engraftable induced oligodendrocytes that expedited myelination within synthetically accelerated cerebral organoids.

2020-10-22 | GSE159784 | GEO