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

doi:10.1038/ncomms6807

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

Nat Commun. 2014 Dec 16:5:5807. doi: 10.1038/ncomms6807.

Authors

Ruifeng Yang¹, Ying Zheng², Ling Li³, Shujing Liu¹, Michelle Burrows², Zhi Wei⁴, Arben Nace², Meenhard Herlyn³, Rutao Cui⁵, Wei Guo⁶, George Cotsarelis², Xiaowei Xu¹

Affiliations

¹ Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
² Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
³ Melanoma Research Center, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
⁴ Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey 07102, USA.
⁵ Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
⁶ Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

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
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
PAX3 Transcription Factor
Paired Box Transcription Factors / genetics
Paired Box Transcription Factors / metabolism
Primary Cell Culture
Retroviridae / genetics
SOXE Transcription Factors / genetics
SOXE Transcription Factors / metabolism
Transfection / methods
Transgenes*

Substances

MITF protein, human
Melanins
Microphthalmia-Associated Transcription Factor
PAX3 Transcription Factor
PAX3 protein, human
Paired Box Transcription Factors
SOX10 protein, human
SOXE Transcription Factors

Associated data

GEO/GSE51028

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding