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Published May 2017 | Supplemental Material + Accepted Version
Journal Article Open

Reprogramming Postnatal Human Epidermal Keratinocytes toward Functional Neural Crest Fates

Abstract

During development, neural crest cells are induced by signaling events at the neural plate border of all vertebrate embryos. Initially arising within the central nervous system, neural crest 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, in response to FGF2 and IGF1 signals, can be reprogrammed toward a neural crest fate. Genome-wide transcriptome analyses show that keratinocyte-derived neural crest cells are similar to those derived from human embryonic stem cells. Moreover, they give rise in vitro and in vivo to neural crest derivatives such as peripheral neurons, melanocytes, Schwann cells and mesenchymal cells (osteocytes, chondrocytes, adipocytes and smooth muscle). By demonstrating that human KRT14+ keratinocytes can form neural crest cells, even from clones of single cells, our results have important implications in stem cell biology and regenerative medicine.

Additional Information

© 2017 AlphaMed Press. Accepted manuscript online: 31 January 2017; Manuscript Accepted: 7 January 2017; Manuscript Revised: 5 December 2016; Manuscript Received: 31 May 2016. This work was supported by grants from the University at Buffalo (IMPACT Award) and National Institutes of Health (R01EB023114) to S.T.A. K.A.C. was supported by Grant F31 NS 084668. G.P. was supported by Grants F31 NS 084668 and AHA 12EIA9100012. M.E.B. was supported by R01DE024157. We thank Deepika Verma for her help in creating schematic diagram. Author Contributions: V.K.B.: conceptualized and designed the study and performed the experiments; V.K.B. and S.T.A.: designed experiments and performed data analysis and interpretation; L.K. and M.E.B.: performed chicken embryo experiments; K.A.C. and G.P.: electrophysiological analysis; G.T., X.W., and P.L.: performed experiments; B.L., S.L., and V.K.B.: RNA sequencing analysis. V.K.B., S.T.A., and M.E.B.: wrote the manuscript; All authors read the manuscript and provided their inputs. Accession Numbers: GEO: GSE72268 The authors indicate no potential conflicts of interest.

Attached Files

Accepted Version - nihms882815.pdf

Supplemental Material - stem2583-sup-0001-suppinfo1.pdf

Supplemental Material - stem2583-sup-0002-suppinfo2.docx

Supplemental Material - stem2583-sup-0003-suppinfoFig1.tiff

Supplemental Material - stem2583-sup-0004-suppinfoFig2.tiff

Supplemental Material - stem2583-sup-0005-suppinfoFig3.tiff

Supplemental Material - stem2583-sup-0006-suppinfoFig4.tiff

Supplemental Material - stem2583-sup-0007-suppinfoFig5.tiff

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Additional details

Created:
August 21, 2023
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October 24, 2023