title: Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Shujing
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Burrows
authors.affiliation: Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey 07102, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Arben
authors.initials: A
authors.lastname: Nace
authors.affiliation: Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.affiliation: Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Rutao
authors.initials: R
authors.lastname: Cui
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: George
authors.initials: G
authors.lastname: Cotsarelis
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D065150:Cellular Reprogramming / Q000235:genetics*; D020405:Dermis / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D005822:Genetic Vectors; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis* / Q000235:genetics; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D020460:Melanosomes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D012190:Retroviridae / Q000235:genetics; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D019076:Transgenes
chemical_list: C497234:MITF protein, human; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors