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, Xiaowei Xu

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

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.

Original languageEnglish (US)
Article number5807
JournalNature communications
Volume5
DOIs
StatePublished - Dec 2014

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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