Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells
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Dear Editor,
We previously developed a novel paradigm of cell activation and signaling-directed (CASD) lineage conversion for direct reprogramming of fibroblasts into cardiac,neural and endothelial precursor cells.This method is based on the transient overexpression of iPSC factors (cell activation,CA) in conjunction with lineage-specific soluble signals (signaling directed,SD).Such a strategy was used to generate human induced neural stem cells (hiNSCs) with 4 to 6 pluripotency factors,including OCT4,SOX2,KLF4 and microRNAs,from cells in human urine [1] and fibroblasts [2].Using a different strategy,SOX2 was found to induce the generation of hiNSCs,although only from fetal fibroblasts with low efficiency and by a tedious process [3].
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JK,H-SK and YSC were supported by the MEST/Stem Cell Research Program [2010-0020272],Basic Science Research Program2012R1A1A2043433;KRCF National Agenda Program,and KRIBB Research Initiative Program.SZ was supported by Gladstone CIRM Scholars Program.RA,MT,JDZ,SS-B,EM,SRM,and SAL were supported by P01 ES016738,P01 HD29587,and P30 NS076411.WS and HJK were supported by Basic Science Research Program 2012M3A9C6049933 through Kore