Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs
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 ac...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713001320 |
| _version_ | 1828530642792480768 |
|---|---|
| author | Yvonne Mica Gabsang Lee Stuart M. Chambers Mark J. Tomishima Lorenz Studer |
| author_facet | Yvonne Mica Gabsang Lee Stuart M. Chambers Mark J. Tomishima Lorenz Studer |
| author_sort | Yvonne Mica |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:26:12Z |
| format | Article |
| id | doaj.art-9a775af0b4554c619264df5fcdcc92e9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T22:26:12Z |
| publishDate | 2013-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-9a775af0b4554c619264df5fcdcc92e92022-12-22T00:48:17ZengElsevierCell Reports2211-12472013-04-01341140115210.1016/j.celrep.2013.03.025Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCsYvonne Mica0Gabsang Lee1Stuart M. Chambers2Mark J. Tomishima3Lorenz Studer4The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USAThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USAThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USAThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USAThe Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USAMelanocytes 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.http://www.sciencedirect.com/science/article/pii/S2211124713001320 |
| spellingShingle | Yvonne Mica Gabsang Lee Stuart M. Chambers Mark J. Tomishima Lorenz Studer Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs Cell Reports |
| title | Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs |
| title_full | Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs |
| title_fullStr | Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs |
| title_full_unstemmed | Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs |
| title_short | Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs |
| title_sort | modeling neural crest induction melanocyte specification and disease related pigmentation defects in hescs and patient specific ipscs |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713001320 |
| work_keys_str_mv | AT yvonnemica modelingneuralcrestinductionmelanocytespecificationanddiseaserelatedpigmentationdefectsinhescsandpatientspecificipscs AT gabsanglee modelingneuralcrestinductionmelanocytespecificationanddiseaserelatedpigmentationdefectsinhescsandpatientspecificipscs AT stuartmchambers modelingneuralcrestinductionmelanocytespecificationanddiseaserelatedpigmentationdefectsinhescsandpatientspecificipscs AT markjtomishima modelingneuralcrestinductionmelanocytespecificationanddiseaserelatedpigmentationdefectsinhescsandpatientspecificipscs AT lorenzstuder modelingneuralcrestinductionmelanocytespecificationanddiseaserelatedpigmentationdefectsinhescsandpatientspecificipscs |