TY - JOUR
T1 - Generation of melanocytes from induced pluripotent stem cells
AU - Yang, Ruifeng
AU - Jiang, Min
AU - Kumar, Suresh M.
AU - Xu, Theodore
AU - Wang, Fei
AU - Xiang, Leihong
AU - Xu, Xiaowei
N1 - Funding Information:
We thank Dr Meenhard Herlyn for providing the Wnt3a cell line; the histology laboratory at the Department of Pathology and Laboratory Medicine, University of Pennsylvania, for tissue processing; and Dr Kristen Huang for editing the manuscript. This work was supported by the grants AR-054593 and AR-054593S1 from the National Institutes of Health to XX.
PY - 2011/12
Y1 - 2011/12
N2 - Epidermal melanocytes have an important role in protecting skin from UV rays, and are implicated in a variety of skin diseases. Here, we developed an efficient method for differentiating induced pluripotent stem cells (iPSCs) into melanocytes. We first generated iPSCs from adult mouse tail-tip fibroblasts (TTFs) using retroviral vectors or virus-free piggyBac transposon vectors carrying murine Sox2, Oct3/4, c-Myc, and Klf4. The TTF-derived iPSC clones exhibited similar morphology and growth properties as mouse embryonic stem (ES) cells. The iPSCs expressed ES cell markers, displayed characteristic epigenetic changes, and formed teratomas with all three germ layers. The iPSCs were used to generate embryonic bodies and were then successfully differentiated into melanocytes by treatment with growth factors. The iPSC-derived melanocytes expressed characteristic melanocyte markers and produced melanin pigment. Electron microscopy showed that the melanocytes contained mature melanosomes. We manipulated the conditions used to differentiate iPSCs to melanocytes and discovered that Wnt3a is not required for mouse melanocyte differentiation. This report shows that melanocytes can be readily generated from iPSCs, providing a powerful resource for the in vitro study of melanocyte developmental biology and diseases. By inducing iPSCs without viruses, the possibility of integration mutagenesis is alleviated, and these iPSCs are more compatible for cell replacement therapies.
AB - Epidermal melanocytes have an important role in protecting skin from UV rays, and are implicated in a variety of skin diseases. Here, we developed an efficient method for differentiating induced pluripotent stem cells (iPSCs) into melanocytes. We first generated iPSCs from adult mouse tail-tip fibroblasts (TTFs) using retroviral vectors or virus-free piggyBac transposon vectors carrying murine Sox2, Oct3/4, c-Myc, and Klf4. The TTF-derived iPSC clones exhibited similar morphology and growth properties as mouse embryonic stem (ES) cells. The iPSCs expressed ES cell markers, displayed characteristic epigenetic changes, and formed teratomas with all three germ layers. The iPSCs were used to generate embryonic bodies and were then successfully differentiated into melanocytes by treatment with growth factors. The iPSC-derived melanocytes expressed characteristic melanocyte markers and produced melanin pigment. Electron microscopy showed that the melanocytes contained mature melanosomes. We manipulated the conditions used to differentiate iPSCs to melanocytes and discovered that Wnt3a is not required for mouse melanocyte differentiation. This report shows that melanocytes can be readily generated from iPSCs, providing a powerful resource for the in vitro study of melanocyte developmental biology and diseases. By inducing iPSCs without viruses, the possibility of integration mutagenesis is alleviated, and these iPSCs are more compatible for cell replacement therapies.
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U2 - 10.1038/jid.2011.242
DO - 10.1038/jid.2011.242
M3 - Article
C2 - 21833016
AN - SCOPUS:80855123830
VL - 131
SP - 2458
EP - 2466
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 12
ER -