title: Human induced pluripotent stem cell-derived ectodermal precursor cells contribute to hair follicle morphogenesis in vivo.
abstract: Well-orchestrated epithelial-mesenchymal interactions are crucial for hair follicle (HF) morphogenesis. In this study, ectodermal precursor cells (EPCs) with the capacity to cross talk with hair-inductive dermal cells were generated from human induced pluripotent stem cells (hiPSCs) and assessed for HF-forming ability in vivo. EPCs derived from three hiPSC lines generated with 4 or 3 factors (POU5F1, SOX2, KLF4 +/- MYC) mostly expressed keratin 18, a marker of epithelial progenitors. When cocultured with human dermal papilla (DP) cells, a 4 factor 201B7 hiPSC-EPC line upregulated follicular keratinocyte (KC) markers more significantly than normal human adult KCs (NHKCs) and other hiPSC-EPC lines. DP cells preferentially increased DP biomarker expression in response to this line. Interestingly, 201B7 hiPSCs were shown to be ectodermal/epithelial prone, and the derived EPCs were putatively in a wingless-type MMTV integration site family (WNT)-activated state. Importantly, co-transplantation of 201B7 hiPSC-EPCs, but not NHKCs, with trichogenic mice dermal cells into immunodeficient mice resulted in HF formation. Human HF stem cell markers were detected in reconstituted HFs; however, a low frequency of human-derived cells implied that hiPSC-EPCs contributed to HF morphogenesis via direct repopulation and non-cell autonomous activities. The current study suggests a, to our knowledge, previously unrecognized advantage of using hiPSCs to enhance epithelial-mesenchymal interactions in HF bioengineering.
authors: Department of Dermatology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan.
authors: Ophelia
authors: O
authors: Veraitch
authors: Tetsuro
authors: T
authors: Kobayashi
authors: Yoichi
authors: Y
authors: Imaizumi
authors: Wado
authors: W
authors: Akamatsu
authors: Takashi
authors: T
authors: Sasaki
authors: Shinya
authors: S
authors: Yamanaka
authors: Masayuki
authors: M
authors: Amagai
authors: Hideyuki
authors: H
authors: Okano
authors: Manabu
authors: M
authors: Ohyama
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D057005:Bioengineering / Q000379:methods; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D018920:Coculture Techniques; D020405:Dermis / Q000166:cytology* / Q000254:growth & development; D004475:Ectoderm / Q000166:cytology* / Q000254:growth & development; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051379:Mice; D009024:Morphogenesis / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration / Q000502:physiology; D016038:Skin Transplantation / Q000379:methods; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D015415:Biomarkers; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4