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

Ruifeng Yang; Ying Zheng; Michelle Burrows; Shujing Liu; Zhi Wei; Arben Nace; Wei Guo; Suresh Kumar; George Cotsarelis; Xiaowei Xu

doi:10.1038/ncomms4071

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

Ruifeng Yang, Ying Zheng, Michelle Burrows, Shujing Liu, Zhi Wei, Arben Nace, Wei Guo, Suresh Kumar, George Cotsarelis, Xiaowei Xu

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

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 + /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.

Original language	English (US)
Article number	3071
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms4071
State	Published - Jan 28 2014
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms4071

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@article{403fe7697322419e93db7d9c95e91145,

title = "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 + /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.",

author = "Ruifeng Yang and Ying Zheng and Michelle Burrows and Shujing Liu and Zhi Wei and Arben Nace and Wei Guo and Suresh Kumar and George Cotsarelis and Xiaowei Xu",

note = "Funding Information: We gratefully acknowledge the histology laboratory at the Department of Pathology and Laboratory Medicine for assistance in histological studies, Penn Flow Cytometry Facility and the Cooperative Human Tissue Network. This research was supported by the US National Institutes of Health grant R01-AR054593, P30-AR057217.",

year = "2014",

month = jan,

day = "28",

doi = "10.1038/ncomms4071",

language = "English (US)",

volume = "5",

journal = "Nature communications",

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T1 - Generation of folliculogenic human epithelial stem cells from induced pluripotent stem cells

AU - Yang, Ruifeng

AU - Zheng, Ying

AU - Burrows, Michelle

AU - Liu, Shujing

AU - Wei, Zhi

AU - Nace, Arben

AU - Guo, Wei

AU - Kumar, Suresh

AU - Cotsarelis, George

AU - Xu, Xiaowei

N1 - Funding Information: We gratefully acknowledge the histology laboratory at the Department of Pathology and Laboratory Medicine for assistance in histological studies, Penn Flow Cytometry Facility and the Cooperative Human Tissue Network. This research was supported by the US National Institutes of Health grant R01-AR054593, P30-AR057217.

PY - 2014/1/28

Y1 - 2014/1/28

N2 - 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.

AB - 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.

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

Abstract

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