A comprehensive library of human transcription factors for cell fate engineering (Lentiviral Screen PGP1)

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. Overall design: This dataset contains the PGP1 hiPSC portion of the paper. This paper describes three hiPSC lines that were transduced with lentiviruses containing the Human TFome. TFs were induced for four days and cells sorted for TRA-1-60 signal. PCR using universal primers amplified TFs from genomic DNA, and PCR products were sequenced.