Human induced pluripotent stem cell-derived ectodermal precursor cells contribute to hair follicle morphogenesis in vivo

Ophelia Veraitch, Tetsuro Kobayashi, Yoichi Imaizumi, Wado Akamatsu, Takashi Sasaki, Shinya Yamanaka, Masayuki Amagai, Hideyuki Okano, Manabu Ohyama

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1479-1488
Number of pages10
JournalJournal of Investigative Dermatology
Volume133
Issue number6
DOIs
Publication statusPublished - 2013 Jun

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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