期刊
STEM CELLS
卷 35, 期 5, 页码 1402-1415出版社
WILEY
DOI: 10.1002/stem.2583
关键词
Neural crest; Epidermal keratinocytes; Neural plate border; Neural crest induction; Reprogramming
资金
- University at Buffalo (IMPACT Award)
- National Institutes of Health [R01EB023114]
- [F31 NS 084668]
- [AHA 12EIA9100012]
- [R01DE024157]
During development, neural crest (NC) cells are induced by signaling events at the neural plate border of all vertebrate embryos. Initially arising within the central nervous system, NC cells subsequently undergo an epithelial to mesenchymal transition to migrate into the periphery, where they differentiate into diverse cell types. Here we provide evidence that postnatal human epidermal keratinocytes (KC), in response to fibroblast growth factor 2 and insulin like growth factor 1 signals, can be reprogrammed toward a NC fate. Genome-wide transcriptome analyses show that keratinocyte-derived NC cells are similar to those derived from human embryonic stem cells. Moreover, they give rise in vitro and in vivo to NC derivatives such as peripheral neurons, melanocytes, Schwann cells and mesenchymal cells (osteocytes, chondrocytes, adipocytes, and smooth muscle cells). By demonstrating that human keratin-14+ KC can form NC cells, even from clones of single cells, our results have important implications in stem cell biology and regenerative medicine. Stem Cells2017;35:1402-1415
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