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Generating trunk neural crest from human pluripotent stem cells

Huang, Miller and Miller, Matthew L. and McHenry, Lauren K. and Zheng, Tina and Zhen, Qiqi and Ilkhanizadeh, Shirin and Conklin, Bruce R. and Bronner, Marianne E. and Weiss, William A. (2016) Generating trunk neural crest from human pluripotent stem cells. Scientific Reports, 6 . Art. No. 19727. ISSN 2045-2322. PMCID PMC4728437. doi:10.1038/srep19727.

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Neural crest cells (NCC) are stem cells that generate different lineages, including neuroendocrine, melanocytic, cartilage, and bone. The differentiation potential of NCC varies according to the level from which cells emerge along the neural tube. For example, only anterior “cranial” NCC form craniofacial bone, whereas solely posterior “trunk” NCC contribute to sympathoadrenal cells. Importantly, the isolation of human fetal NCC carries ethical and scientific challenges, as NCC induction typically occur before pregnancy is detectable. As a result, current knowledge of NCC biology derives primarily from non-human organisms. Important differences between human and non-human NCC, such as expression of HNK1 in human but not mouse NCC, suggest a need to study human NCC directly. Here, we demonstrate that current protocols to differentiate human pluripotent stem cells (PSC) to NCC are biased toward cranial NCC. Addition of retinoic acid drove trunk-related markers and HOX genes characteristic of a posterior identity. Subsequent treatment with bone morphogenetic proteins (BMPs) enhanced differentiation to sympathoadrenal cells. Our approach provides methodology for detailed studies of human NCC, and clarifies roles for retinoids and BMPs in the differentiation of human PSC to trunk NCC and to sympathoadrenal lineages.

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Bronner, Marianne E.0000-0003-4274-1862
Additional Information:© 2016 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit received: 17 August 2015. accepted: 17 December 2015. Published: 27 January 2016. WAW was supported by NIH grants: U01U01CA176287, P30CA82103, R01NS088355, R01CA102321, and by grants from the Alex’s Lemonade Stand, Katie Dougherty, Ross K. MacNeill, and Samuel G. Waxman Foundations, and a CureSearch Grand Challenge Award. MH was supported by a Postdoctoral Fellowship, PF-13-295-01–TBG from the American Cancer Society, and an Alex’s Lemonade Stand Foundation Young Investigator Award. SI was supported by the Swedish Brain Tumor Foundation and the Swedish Childhood Cancer Foundation. MEB was supported by NIH grant R01DE024157. BRC was supported by NIH grants: U01HL099997, P01HL089707, and R01HL060664. Author Contributions: M.H. designed and performed experiments, analyzed data, and wrote the manuscript. M.L.M., L.K.M., T.Z. and Q.Z. performed experiments and analyzed data. S.I. assisted in statistical analysis and quantification of immunofluorescence. B.R.C. and M.E.B. designed experiments and wrote the manuscript. W.A.W. supervised the study and wrote the manuscript. The authors declare no competing financial interests.
Funding AgencyGrant Number
Alex's Lemonade Stand Foundation for Childhood CancerUNSPECIFIED
CureSearch Grand Challenge AwardUNSPECIFIED
American Cancer SocietyPF-13-295-01–TBG
Swedish Brain Tumor FoundationUNSPECIFIED
Swedish Childhood Cancer FoundationUNSPECIFIED
Katie DoughertyUNSPECIFIED
Samuel G. Waxman FoundationUNSPECIFIED
Ross K. MacNeill FoundationUNSPECIFIED
PubMed Central ID:PMC4728437
Record Number:CaltechAUTHORS:20160203-070724904
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Official Citation:Generating trunk neural crest from human pluripotent stem cells Miller Huang, Matthew L. Miller, William A. Weiss Scientific Reports 6, 19727 (2016)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64178
Deposited By: Ruth Sustaita
Deposited On:03 Feb 2016 20:26
Last Modified:10 Nov 2021 23:27

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