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Reprogramming Postnatal Human Epidermal Keratinocytes toward Functional Neural Crest Fates

Bajpai, Vivek K. and Kerosuo, Laura and Tseropoulos, Georgios and Cummings, Kirstie A. and Wang, Xiaoyan and Lei, Pedro and Liu, Biao and Liu, Song and Popescu, Gabriela and Bronner, Marianne E. and Andreadis, Stelios T. (2017) Reprogramming Postnatal Human Epidermal Keratinocytes toward Functional Neural Crest Fates. Stem Cells, 35 (5). pp. 1402-1415. ISSN 1066-5099. PMCID PMC5543412. https://resolver.caltech.edu/CaltechAUTHORS:20170206-083642837

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/stem.2583DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543412PubMed CentralArticle
ORCID:
AuthorORCID
Kerosuo, Laura0000-0001-6710-3512
Bronner, Marianne E.0000-0003-4274-1862
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.
Funders:
Funding AgencyGrant Number
University at BuffaloUNSPECIFIED
NIHR01EB023114
NIHR01DE024157
NIHAHA 12EIA9100012
Subject Keywords:Neural crest; Epidermal keratinocytes; Neural plate border; Neural crest induction; Reprogramming
Issue or Number:5
PubMed Central ID:PMC5543412
Record Number:CaltechAUTHORS:20170206-083642837
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20170206-083642837
Official Citation:Bajpai, V. K., Kerosuo, L., Tseropoulos, G., Cummings, K. A., Wang, X., Lei, P., Liu, B., Liu, S., Popescu, G. K., Bronner, M. E. and Andreadis, S. T. (2017), Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates. Stem Cells, 35: 1402–1415. doi:10.1002/stem.2583
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74061
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Feb 2017 18:04
Last Modified:03 Oct 2019 16:34

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