title: Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates.
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.
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Bajpai
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Laura
authors.identifier: 0000-0001-6710-3512
authors.initials: L
authors.lastname: Kerosuo
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Tseropoulos
authors.affiliation: Department of Biochemistry, Neuroscience Program, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
authors.forename: Kirstie A
authors.initials: KA
authors.lastname: Cummings
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Lei
authors.affiliation: Center for Personalized Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.|Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Center for Personalized Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.|Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, Neuroscience Program, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, USA.
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Popescu
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA.
authors.forename: Marianne E
authors.initials: ME
authors.lastname: Bronner
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, Buffalo, New York, USA.|Department of Biomedical Engineering, University at Buffalo, Buffalo, New York, USA.|Center of Excellence in Bioinformatics and Life Sciences, Buffalo, New York, USA.
authors.forename: Stelios T
authors.initials: ST
authors.lastname: Andreadis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D065150:Cellular Reprogramming / Q000235:genetics; D002999:Clone Cells; D000078404:Epidermal Cells; D020869:Gene Expression Profiling; D000066449:Human Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology; D009432:Neural Crest / Q000166:cytology*; D054258:Neural Plate / Q000166:cytology; D014158:Transcription, Genetic
keywords: Epidermal keratinocytes; Neural crest; Neural crest induction; Neural plate border; Reprogramming