State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Cell Res. 2014 Jun;24(6):665-79. doi: 10.1038/cr.2014.32. Epub 2014 Mar 18.
Neural progenitor cells (NPCs) can be induced from somatic cells by defined factors. Here we report that NPCs can be generated from mouse embryonic fibroblasts by a chemical cocktail, namely VCR (V, VPA, an inhibitor of HDACs; C, CHIR99021, an inhibitor of GSK-3 kinases and R, Repsox, an inhibitor of TGF-β pathways), under a physiological hypoxic condition. These chemical-induced NPCs (ciNPCs) resemble mouse brain-derived NPCs regarding their proliferative and self-renewing abilities, gene expression profiles, and multipotency for different neuroectodermal lineages in vitro and in vivo. Further experiments reveal that alternative cocktails with inhibitors of histone deacetylation, glycogen synthase kinase, and TGF-β pathways show similar efficacies for ciNPC induction. Moreover, ciNPCs can also be induced from mouse tail-tip fibroblasts and human urinary cells with the same chemical cocktail VCR. Thus our study demonstrates that lineage-specific conversion of somatic cells to NPCs could be achieved by chemical cocktails without introducing exogenous factors.
神经祖细胞（NPCs）可以通过特定的因子从体细胞中诱导产生。在这里，我们报告说，NPCs 可以通过一种化学鸡尾酒（即 VCR[V、VPA，组蛋白去乙酰化酶抑制剂；C、CHIR99021，GSK-3 激酶抑制剂；R、Repsox，TGF-β 通路抑制剂]）在生理缺氧条件下从小鼠胚胎成纤维细胞中产生。这些化学诱导的 NPC（ciNPCs）在增殖和自我更新能力、基因表达谱以及体外和体内不同神经外胚层谱系的多能性方面与源自小鼠大脑的 NPC 相似。进一步的实验表明，具有组蛋白去乙酰化酶抑制剂、糖原合成酶激酶抑制剂和 TGF-β 通路抑制剂的替代鸡尾酒对于 ciNPC 诱导具有相似的功效。此外，使用相同的 VCR 化学鸡尾酒也可以从小鼠尾尖成纤维细胞和人尿细胞中诱导 ciNPC。因此，我们的研究表明，通过化学鸡尾酒可以在不引入外源因子的情况下实现体细胞向 NPC 的谱系特异性转化。
