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Early Acquisition of Neural Crest Competence During hESCs Neuralization

Curchoe, Carol Lynn and Maurer, Jochen and McKeown, Sonja J. and Cattarossi, Giulio and Cimadamore, Flavio and Nilbratt, Mats and Snyder, Evan Y. and Bronner-Fraser, Marianne and Terskikh, Alexey V. (2010) Early Acquisition of Neural Crest Competence During hESCs Neuralization. PLoS ONE, 5 (11). Art. No. e13890. ISSN 1932-6203. PMCID PMC2976694.

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Background: Neural crest stem cells (NCSCs) are a transient multipotent embryonic cell population that represents a defining characteristic of vertebrates. The neural crest (NC) gives rise to many derivatives including the neurons and glia of the sensory and autonomic ganglia of the peripheral nervous system, enteric neurons and glia, melanocytes, and the cartilaginous, bony and connective tissue of the craniofacial skeleton, cephalic neuroendocrine organs, and some heart vessels. Methodology/Principal Findings: We present evidence that neural crest (NC) competence can be acquired very early when human embryonic stem cells (hESCs) are selectively neuralized towards dorsal neuroepithelium in the absence of feeder cells in fully defined conditions. When hESC-derived neurospheres are plated on fibronectin, some cells emigrate onto the substrate. These early migratory Neural Crest Stem Cells (emNCSCs) uniformly upregulate Sox10 and vimentin, downregulate N-cadherin, and remodel F-actin, consistent with a transition from neuroepithelium to a mesenchymal NC cell. Over 13% of emNCSCs upregulate CD73, a marker of mesenchymal lineage characteristic of cephalic NC and connexin 43, found on early migratory NC cells. We demonstrated that emNCSCs give rise in vitro to all NC lineages, are multipotent on clonal level, and appropriately respond to developmental factors. We suggest that human emNCSC resemble cephalic NC described in model organisms. Ex vivo emNCSCs can differentiate into neurons in Ret.k- mouse embryonic gut tissue cultures and transplanted emNCSCs incorporate into NC-derived structures but not CNS tissues in chick embryos. Conclusions/Significance: These findings will provide a framework for further studying early human NC development including the epithelial to mesenchymal transition during NC delamination.

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Bronner-Fraser, Marianne0000-0003-4274-1862
Additional Information:© 2010 Curchoe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received April 7, 2010; Accepted September 23, 2010; Published November 9, 2010. Editor: Joseph Najbauer, City of Hope National Medical Center, United States of America. Funded by California Institute for Regenerative Medicine Seed grant RS1-00466-1 to Alexey V. Terskikh. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist. The authors would like to thank A. Miller and J. Lesperance for the help with hESC cultures, R. Bajpai for RNA preparation, Y. Altman for assistance with FACS sorting, K. Liu for microarray and Q-PCR assistance, L. Creighton for help with the immunhistochemistry on chondrocytes, D. Arce and M. Jones for assistance with cryosectioning, M. Wegner and M. Fukuda for provision of antibodies, R. Gupta and M. Mercola for providing the DKK plasmid, T. Cheung for DKK media preparation, E. Chavez and A. Ryan for providing timed pregnant Ret.k- mice. Author Contributions: Conceived and designed the experiments: MBF AVT. Performed the experiments: CLC JM SM GC FC MN. Analyzed the data: SM ES MBF AVT. Contributed reagents/materials/analysis tools: ES MBF AVT. Wrote the paper: CLC JM AVT.
Funding AgencyGrant Number
California Institute for Regenerative Medicine (CIRM)RS1-00466-1
Issue or Number:11
PubMed Central ID:PMC2976694
Record Number:CaltechAUTHORS:20101207-091550174
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Official Citation:Curchoe CL, Maurer J, McKeown SJ, Cattarossi G, Cimadamore F, et al. 2010 Early Acquisition of Neural Crest Competence During hESCs Neuralization. PLoS ONE 5(11): e13890. doi:10.1371/journal.pone.0013890
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:21208
Deposited By: Tony Diaz
Deposited On:10 Dec 2010 22:22
Last Modified:03 Oct 2019 02:21

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