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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Ruifeng Yang & Ying Zheng & Ling Li & Shujing Liu & Michelle Burrows & Zhi Wei & Arben Nace & Meenhard Herlyn & Rutao Cui & Wei Guo & George Cotsarelis & Xiaowei Xu, 2014. "Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6807
    DOI: 10.1038/ncomms6807
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