Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

Abstract

Epithelial stem cells (EpSCs) in the hair follicle bulge are required for hair follicle growth and cycling. The isolation and propagation of human EpSCs for tissue engineering purposes remains a challenge. Here we develop a strategy to differentiate human iPSCs (hiPSCs) into CD200 þ /ITGA6 þ EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200 þ /ITGA6 þ cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSCderived CD200 þ /ITGA6 þ cells are capable of generating all hair follicle lineages including the hair shaft, and the inner and outer root sheaths in skin reconstitution assays. The regenerated hair follicles possess a KRT15 þ stem cell population and produce hair shafts expressing hair-specific keratins. These results suggest an approach for generating large numbers of human EpSCs for tissue engineering and new treatments for hair loss, wound healing and other degenerative skin disorders.

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells

“…Bulge cells contribute not only to the generation of new HFs with each hair cycle but also to the repair of the epidermis during wound healing [8–9]. To obtain epithelial SCs, human epidermal keratinocytes and epidermal SCs have been developed from induced pluripotent stem cells (iPSCs) [10–12]. Additionally, iPSCs-derived epidermal cells have the ability to reconstitute HFs with mouse dermal cells [12, 13].…”

Hair Follicle Reconstruction and Stem Cells

“…Using the advantage of induced pluripotency Yang with colleagues [105] obtained folliculogenic CD200+/ITGA6+ epidermal stem cells from human ibroblast-derived induced pluripotent cells. Patch in vivo assay demonstrated the ability of these cells to generate all HF lineages including the hair shaft, and the inner and outer root sheaths.…”

Modeling Cancer with Pluripotent Stem Cells

“…PSC differentiation protocols have been established for generation of hepatic cells [42–44], intestinal tissue [45], thyroid follicular cells [46], airway epithelial cells [47–49], renal progenitor cells [50, 51], retinal cells [52–55], epithelial stem cells [56], epidermal keratinocytes [57], myeloid cells [58, 59], neurons [34, 60], MSCs [61], and melanocytes [62], among many others. Application of these protocols to cancer patient-derived iPSCs and engineered ESCs should allow research of cancers of these organs.…”