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Cell Rep. 2013 Apr 25;3(4):1140-52. doi: 10.1016/j.celrep.2013.03.025. Epub 2013 Apr 11.

Modeling neural crest induction, melanocyte specification, and disease-related pigmentation defects in hESCs and patient-specific iPSCs.

Author information

1
The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA.

Abstract

Melanocytes are pigment-producing cells of neural crest (NC) origin that are responsible for protecting the skin against UV irradiation. Pluripotent stem cell (PSC) technology offers a promising approach for studying human melanocyte development and disease. Here, we report that timed exposure to activators of WNT, BMP, and EDN3 signaling triggers the sequential induction of NC and melanocyte precursor fates under dual-SMAD-inhibition conditions. Using a SOX10::GFP human embryonic stem cell (hESC) reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human NC induction. Subsequent maturation of hESC-derived melanocytes yields pure populations that match the molecular and functional properties of adult melanocytes. Melanocytes from Hermansky-Pudlak syndrome and Chediak-Higashi syndrome patient-specific induced PSCs (iPSCs) faithfully reproduce the ultrastructural features of disease-associated pigmentation defects. Our data define a highly specific requirement for WNT signaling during NC induction and enable the generation of pure populations of human iPSC-derived melanocytes for faithful modeling of pigmentation disorders.

PMID:
23583175
PMCID:
PMC3681528
DOI:
10.1016/j.celrep.2013.03.025
[Indexed for MEDLINE]
Free PMC Article
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