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The isolation or in vitro derivation of many human cell types remains challenging and inefficient. Direct conversion of human pluripotent stem cells (hPSCs) by forced expression of transcription factors provides a potential alternative. However, deficient inducible gene expression in hPSCs has compromised efficiencies of forward programming approaches.

We have systematically optimized inducible gene expression in hPSCs using a dual genomic safe harbor gene-targeting strategy. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes.