Journal
CELL RESEARCH
Volume 24, Issue 6, Pages 665-679Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2014.32
Keywords
lineage conversion; neural progenitor cells; chemical cocktails; hypoxia
Categories
Funding
- Chinese Academy of Sciences [XDA01010302, 2012KIP301]
- Ministry of Science and Technology [2014CB964802, 2011CB910202]
- National Natural Science Foundation of China [31371419, 31301129]
- Shanghai Municipal Commission for Science and Technology [12ZR1452300]
- Ministry of Health [2012BAI10B03]
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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-beta 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-beta 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.
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