Anne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Clinical Neuroscience, University of Cambridge, Cambridge CB2 0QQ, UK.
Anne McLaren Laboratory, Wellcome Trust-MRC Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0QQ, UK.
Stem Cell Reports. 2017 Apr 11;8(4):803-812. doi: 10.1016/j.stemcr.2017.02.016. Epub 2017 Mar 23.
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. This approach provides a powerful platform for the generation of human cell types by forward programming. We report robust and deterministic reprogramming of hPSCs into neurons and functional skeletal myocytes. Finally, we present a forward programming strategy for rapid and highly efficient generation of human oligodendrocytes.
许多人类细胞类型的分离或体外衍生仍然具有挑战性和效率低下。通过强制表达转录因子将人类多能干细胞（hPSC）直接转化提供了一种潜在的替代方法。然而，hPSC 中诱导型基因表达的不足降低了正向编程方法的效率。我们使用双基因组安全港基因靶向策略系统地优化了 hPSC 中的诱导型基因表达。这种方法为通过正向编程产生人类细胞类型提供了一个强大的平台。我们报告了 hPSC 向神经元和功能性骨骼肌细胞的强大和确定性重编程。最后，我们提出了一种快速且高效产生人类少突胶质细胞的正向编程策略。
