Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells.
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(+)/ITGA6(+) EpSCs that can reconstitute the epithelial components of the hair follicle and interfollicular epidermis. The hiPSC-derived CD200(+)/ITGA6(+) cells show a similar gene expression signature as EpSCs directly isolated from human hair follicles. Human iPSC-derived CD200(+)/ITGA6(+) 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(+) 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.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Ruifeng
R
Yang
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Ying
Y
Zheng
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Michelle
M
Burrows
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Shujing
S
Liu
Department of Computer Science, New Jersey Institute of Technology, Newark, New Jersey 07102, USA.
Zhi
Z
Wei
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Arben
A
Nace
Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Wei
W
Guo
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Suresh
S
Kumar
Department of Dermatology, Kligman Laboratories, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
George
G
Cotsarelis
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Xiaowei
X
Xu
D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D039503:Integrin alpha6 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000503:physiopathology; D023822:Tissue Engineering / Q000379:methods
D015703:Antigens, CD; C588002:ITGA6 protein, human; D039503:Integrin alpha6; C042739:antigens, CD200