title: Functional melanocytes are readily reprogrammable from multilineage-differentiating stress-enduring (muse) cells, distinct stem cells in human fibroblasts.
abstract: The induction of melanocytes from easily accessible stem cells has attracted attention for the treatment of melanocyte dysfunctions. We found that multilineage-differentiating stress-enduring (Muse) cells, a distinct stem cell type among human dermal fibroblasts, can be readily reprogrammed into functional melanocytes, whereas the remainder of the fibroblasts do not contribute to melanocyte differentiation. Muse cells can be isolated as cells positive for stage-specific embryonic antigen-3, a marker for undifferentiated human embryonic stem cells, and differentiate into cells representative of all three germ layers from a single cell, while also being nontumorigenic. The use of certain combinations of factors induces Muse cells to express melanocyte markers such as tyrosinase and microphthalmia-associated transcription factor and to show positivity for the 3,4-dihydroxy-L-phenylalanine reaction. When Muse cell-derived melanocytes were incorporated into three-dimensional (3D) cultured skin models, they localized themselves in the basal layer of the epidermis and produced melanin in the same manner as authentic melanocytes. They also maintained their melanin production even after the 3D cultured skin was transplanted to immunodeficient mice. This technique may be applicable to the efficient production of melanocytes from accessible human fibroblasts by using Muse cells, thereby contributing to autologous transplantation for melanocyte dysfunctions, such as vitiligo.
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. Electronic address: tutiviola@med.tohoku.ac.jp.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Tsuchiyama
authors.affiliation: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Wakao
authors.affiliation: Department of Anthropology and Anatomy, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kuroda
authors.affiliation: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ogura
authors.affiliation: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nojima
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Natsue
authors.initials: N
authors.lastname: Sawaya
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Kenshi
authors.initials: K
authors.lastname: Yamasaki
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Setsuya
authors.initials: S
authors.lastname: Aiba
authors.affiliation: Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; Department of Anthropology and Anatomy, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. Electronic address: mdezawa@med.tohoku.ac.jp.
authors.forename: Mari
authors.initials: M
authors.lastname: Dezawa
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D016038:Skin Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D008543:Melanins