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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 24 JUL 2012
Copyright © 2012 AlphaMed Press
Volume 30, Issue 8, pages 1781–1785, August 2012
How to Cite
Nagao, K., Kobayashi, T., Ohyama, M., Akiyama, H., Horiuchi, K. and Amagai, M. (2012), Brief Report: Requirement of TACE/ADAM17 for Hair Follicle Bulge Niche Establishment. STEM CELLS, 30: 1781–1785. doi: 10.1002/stem.1153
Author contributions: K.N.: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; T.K.: conception and design, collection and/or assembly of data, and data analysis and interpretation; M.O.: data analysis and interpretation; H.A.: provision of study material (Sox9-Cre mice); K.H.: conception and design and collection and/or assembly of data; M.A.: administrative support, financial support, data analysis and interpretation, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS June 13, 2012.
- Issue published online: 24 JUL 2012
- Article first published online: 24 JUL 2012
- Accepted manuscript online: 13 JUN 2012 02:57PM EST
- Manuscript Accepted: 15 MAY 2012
- Manuscript Received: 29 AUG 2011
- Ministry of Education, Culture, Sports, Science
- Technology of Japan, Research for Prevention
- Treatment of Immune/Allergic Diseases
- Ministry of Health, Labor
- Welfare of Japan, Keio Gijuku Academic Development Funds
- Keio University Kanrinmaru Project
- Hair follicles;
- Stem cells;
Hair follicles (HFs) are equipped with stem cell niches that allow regeneration. Tumor necrosis factor-α converting enzyme (TACE), also known as A disintegrin and metalloproteinase 17, is a proteolytic enzyme that regulates a variety of cell surface molecules including TNF-α, via ectodomain shedding. We found TACE expression on mouse HFs and conditionally depleted it in cells that expressed sex-determining region Y-related high-mobility-group box 9 (SOX9) transcription factor, an HF stem cell transcription factor (Taceflox/flox-Sox9-Cre, hereafter, “Tace/Sox9”). Tace/Sox9 mice were born with brittle hair with prolonged anagen phase. They underwent diffuse, progressive, and ultimately whole-body hair loss by 20 weeks old. Tace/Sox9 HFs lacked CD34+ bulge cells as demonstrated via immunofluorescence microscopy and flow cytometry. Real-time PCR revealed downregulation of transcription factors Sox9, Lhx2, and Gata3 and upregulation of Lef1. In vitro colony-forming capacity was abolished in Tace/Sox9 keratinocytes, and HFs exhibited increased proliferation in situ, collectively demonstrating that Tace/Sox9 mice failed to establish the bulge niche and to maintain “stemness” of HF stem cells. Epidermal growth factor receptor (EGFR) signaling was impaired in Tace/Sox9 keratinocytes, and mice depleted of Egfr in SOX9-expressing tissues exhibited hair phenotype nearly identical to Tace/Sox9 mice, demonstrating EGFR signaling as a pathway downstream of TACE in HF homeostasis. This study provides mechanistic implication for human TACE-deficiency and for hair abnormality caused by EGFR inhibitors. STEM CELLS2012;30:1781–1785