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

• Published in: Nature communications 2014-12, Vol.5 (1), p.5807-5807, Article 5807
• Main Authors: Yang, Ruifeng, Zheng, Ying, Li, Ling, Liu, Shujing, Burrows, Michelle, Wei, Zhi, Nace, Arben, Herlyn, Meenhard, Cui, Rutao, Guo, Wei, Cotsarelis, George, Xu, Xiaowei
• Format: Article
• Language: English
• Subjects: 13; 13/100; 13/106; 13/109; 13/31; 14/28; 14/32; 14/34; 14/35; 14/63; 38; 38/15; 38/39; 38/77; 631/136; 631/80/86; 64/110; 64/60; 692/308; Animals; Cell Culture Techniques; Cell Differentiation; Cellular Reprogramming - genetics; Dermis - cytology; Dermis - metabolism; Fibroblasts - cytology; Fibroblasts - metabolism; Gene Expression; Genetic Vectors; Hair Follicle - cytology; Hair Follicle - metabolism; Humanities and Social Sciences; Humans; Keratinocytes - cytology; Keratinocytes - metabolism; Melanins - biosynthesis; Melanins - genetics; Melanocytes - cytology; Melanocytes - metabolism; Melanosomes - genetics; Melanosomes - metabolism; Mice; Mice, Transgenic; Microphthalmia-Associated Transcription Factor - genetics; Microphthalmia-Associated Transcription Factor - metabolism; multidisciplinary; Paired Box Transcription Factors - genetics; Paired Box Transcription Factors - metabolism; PAX3 Transcription Factor; Primary Cell Culture; Retroviridae - genetics; Science; Science (multidisciplinary); SOXE Transcription Factors - genetics; SOXE Transcription Factors - metabolism; Transfection - methods; Transgenes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms6807

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. Some skin pigment disorders such as vitiligo are caused by the loss of melanocytes, the pigment-producing cells in the skin. Here the authors present an approach to directly convert mouse and human dermal fibroblasts into functional melanocytes.