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Stem Cells. 2017 May;35(5):1402-1415. doi: 10.1002/stem.2583. Epub 2017 Mar 5.

Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates.

Author information

1
Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
3
Department of Biochemistry, Neuroscience Program, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
4
Center for Personalized Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.
5
Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.
6
Department of Biomedical Engineering, University at Buffalo, Buffalo, New York, USA.
7
Center of Excellence in Bioinformatics and Life Sciences, Buffalo, New York, USA.

Abstract

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 Cells 2017;35:1402-1415.

KEYWORDS:

Epidermal keratinocytes; Neural crest; Neural crest induction; Neural plate border; Reprogramming

PMID:
28142205
PMCID:
PMC5543412
DOI:
10.1002/stem.2583
[Indexed for MEDLINE]
Free PMC Article

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