Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2458-2466 |
| Number of pages | 9 |
| Journal | Journal of Investigative Dermatology |
| Volume | 131 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2011 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Dermatology
- Cell Biology
Cite this
Generation of melanocytes from induced pluripotent stem cells. / Yang, Ruifeng; Jiang, Min; Kumar, Suresh M.; Xu, Theodore; Wang, Fei; Xiang, Leihong; Xu, Xiaowei.
In: Journal of Investigative Dermatology, Vol. 131, No. 12, 12.2011, p. 2458-2466.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=80855123830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80855123830&partnerID=8YFLogxK
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 -