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Series GSE45223 Query DataSets for GSE45223
Status Public on Jun 01, 2013
Title Genome-wide analysis of differential gene expression in human embryonic stem cell-derived central nervous system, neural crest, and progenitor populations over time
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Melanocytes are pigment-producing cells of neural crest origin responsible for protecting the skin against UV-irradiation. Melanocyte dysfunction leads to pigmentation defects including albinism, vitiligo, and piebaldism and is a key feature of systemic pathologies such as Hermansky-Pudlak (HP) and Chediak-Higashi (CH) Syndromes. Pluripotent stem cell technology offers a novel 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 neural crest and melanocyte precursor fates under dual-SMAD inhibition conditions. Using a SOX10::GFP hESC reporter line, we demonstrate that the temporal onset of WNT activation is particularly critical for human neural crest induction. Surprisingly, suppression of BMP signaling does reduce neural crest yield. Subsequent differentiation of hESC-derived melanocyte precursors under defined conditions yields pure populations of pigmented cells matching the molecular and functional properties of adult melanocytes. Melanocytes from patient-specific iPSCs faithfully reproduce the ultrastructural features of the HP- and CH-specific pigmentation defects with minimal variability across lines. Our data define a highly specific requirement for WNT signaling during neural crest induction and enable the generation of pure populations of hiPSC-derived melanocytes for faithful modeling of human pigmentation disorders.
 
Overall design Total RNA obtained from a timecourse of Dual SMAD Inhibition (DSi), Neural Crest (NC), and Melanocyte (BE) differentiation of human embryonic stem cells in triplicate.
 
Contributor(s) Mica Y, Lee G, Chambers SM, Tomishima M, Studer L
Citation(s) 23583175
Submission date Mar 15, 2013
Last update date Jul 20, 2016
Contact name Yvonne Mica
E-mail(s) grubery@mskcc.org
Organization name Memorial Sloan-Kettering Cancer Center
Street address 1275 York Avenue
City New York
State/province NY
ZIP/Postal code 10021
Country USA
 
Platforms (1)
GPL10904 Illumina HumanHT-12 V4.0 expression beadchip (gene symbol)
Samples (36)
GSM1099386 SD26_d0
GSM1099387 SD26_d1
GSM1099388 SD26LSB_d3
This SubSeries is part of SuperSeries:
GSE45227 Genome-wide analysis of gene expression in melanocytes derived from human embryonic stem cells and patient specific induced pluripotent stem cells
Relations
BioProject PRJNA193273

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE45223_non-normalized.txt.gz 10.3 Mb (ftp)(http) TXT
Processed data included within Sample table

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