Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors

Ruifeng Yang, Ying Zheng, Ling Li, Shujing Liu, Michelle Burrows, Zhi Wei, Arben Nace, Meenhard Herlyn, Rutao Cui, Wei Guo, George Cotsarelis and Xiaowei Xu ()
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Ruifeng Yang: Perelman School of Medicine, University of Pennsylvania
Ying Zheng: Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania
Ling Li: Melanoma Research Center, The Wistar Institute
Shujing Liu: Perelman School of Medicine, University of Pennsylvania
Michelle Burrows: Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania
Zhi Wei: New Jersey Institute of Technology
Arben Nace: Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania
Meenhard Herlyn: Melanoma Research Center, The Wistar Institute
Rutao Cui: Boston University School of Medicine
Wei Guo: University of Pennsylvania
George Cotsarelis: Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania
Xiaowei Xu: Perelman School of Medicine, University of Pennsylvania

Nature Communications, 2014, vol. 5, issue 1, 1-12

Abstract: Abstract Direct reprogramming provides a fundamentally new approach for the generation of patient-specific cells. Here, by screening a pool of candidate transcription factors, we identify that a combination of the three factors, MITF, SOX10 and PAX3, directly converts mouse and human fibroblasts to functional melanocytes. Induced melanocytes (iMels) activate melanocyte-specific networks, express components of pigment production and delivery system and produce melanosomes. Human iMels properly integrate into the dermal–epidermal junction and produce and deliver melanin pigment to surrounding keratinocytes in a 3D organotypic skin reconstruct. Human iMels generate pigmented epidermis and hair follicles in skin reconstitution assays in vivo. The generation of iMels has important implications for studies of melanocyte lineage commitment, pigmentation disorders and cell replacement therapies.

Date: 2014
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DOI: 10.1038/ncomms6807

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