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

J Invest Dermatol. 2013 Jun;133(6):1479-88. doi: 10.1038/jid.2013.7. Epub 2013 Jan 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Animals, Newborn
  • Bioengineering / methods
  • Biomarkers / metabolism
  • Cell Differentiation / physiology
  • Cell Line
  • Coculture Techniques
  • Dermis / cytology*
  • Dermis / growth & development
  • Ectoderm / cytology*
  • Ectoderm / growth & development
  • Epithelial-Mesenchymal Transition / physiology
  • Hair Follicle / cytology*
  • Hair Follicle / growth & development
  • Humans
  • Keratinocytes / cytology*
  • Keratinocytes / metabolism
  • Mice
  • Morphogenesis / physiology
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Regeneration / physiology
  • Skin Transplantation / methods
  • Wnt Signaling Pathway / physiology

Substances

  • Biomarkers