Brief Report: Requirement of TACE/ADAM17 for Hair Follicle Bulge Niche Establishment123. (24th July 2012)

• Record Type: Journal Article
• Authors: Nagao, Keisuke; Kobayashi, Tetsuro; Ohyama, Manabu; Akiyama, Haruhiko; Horiuchi, Keisuke; Amagai, Masayuki
• Is Part Of: Stem cells. Volume 30:Number 8(2012)
• Page Start: 1781
• Page End: 1785
• Publication Date: 2012-07-24
• Subjects: Hair -- Hair follicles -- Stem cells -- TACE/ADAM17 -- SOX9 -- Alopecia; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1153
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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 ( Tace flox/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 CELLS 2012;30:1781–1785