Epidermal melanocytes play an important role in protecting the skin from UV 
rays, and their functional impairment results in pigment disorders. 
Additionally, melanomas are considered to arise from mutations that accumulate 
in melanocyte stem cells. The mechanisms underlying melanocyte differentiation 
and the defining characteristics of melanocyte stem cells in humans are, 
however, largely unknown. In the present study, we set out to generate 
melanocytes from human iPS cells in vitro, leading to a preliminary 
investigation of the mechanisms of human melanocyte differentiation. We 
generated iPS cell lines from human dermal fibroblasts using the Yamanaka 
factors (SOX2, OCT3/4, and KLF4, with or without c-MYC). These iPS cell lines 
were subsequently used to form embryoid bodies (EBs) and then differentiated 
into melanocytes via culture supplementation with Wnt3a, SCF, and ET-3. Seven 
weeks after inducing differentiation, pigmented cells expressing melanocyte 
markers such as MITF, tyrosinase, SILV, and TYRP1, were detected. Melanosomes 
were identified in these pigmented cells by electron microscopy, and global gene 
expression profiling of the pigmented cells showed a high similarity to that of 
human primary foreskin-derived melanocytes, suggesting the successful generation 
of melanocytes from iPS cells. This in vitro differentiation system should prove 
useful for understanding human melanocyte biology and revealing the mechanism of 
various pigment cell disorders, including melanoma.