Modeling neural crest induction, melanocyte specification, and disease-related pigmentation defects in hESCs and patient-specific iPSCs Journal Article
| Authors: | Mica, Y.; Lee, G.; Chambers, S. M.; Tomishima, M. J.; Studer, L. |
| Article Title: | Modeling neural crest induction, melanocyte specification, and disease-related pigmentation defects in hESCs and patient-specific iPSCs |
| 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. © 2013 The Authors. |
| Keywords: | signal transduction; controlled study; human cell; models, biological; cell maturation; melanocyte; melanocytes; bone morphogenetic protein; embryonic stem cell; cell differentiation; cell lineage; cell specificity; pigmentation; glycogen synthase kinase 3beta; cell isolation; embryonic stem cells; green fluorescent proteins; neural crest; pluripotent stem cell; wnt proteins; wnt protein; induced pluripotent stem cells; bone morphogenetic proteins; glycogen synthase kinase 3; pigment disorder; cell ultrastructure; melanosome; ocular albinism; endothelin 3; chediak higashi syndrome; melanoblast; chediak-higashi syndrome; endothelin-3; hermanski-pudlak syndrome; soxe transcription factors |
| Journal Title: | Cell Reports |
| Volume: | 3 |
| Issue: | 4 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2013-04-25 |
| Start Page: | 1140 |
| End Page: | 1152 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2013.03.025 |
| PROVIDER: | scopus |
| PUBMED: | 23583175 |
| PMCID: | PMC3681528 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 June 2013" - "Source: Scopus" |
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