Research Article

Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis

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Science  05 Feb 2016:
Vol. 351, Issue 6273, aad4395
DOI: 10.1126/science.aad4395

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  • RE: Persisting chromatin damage is the driving force of stem cell aging in hair follicles
    • Claudia E. Rübe, Head of the laboratory, Department of Radiation Oncology, Saarland University, Germany

    Matsumura et al. analyzed hair follicle stem cells (HFSCs) in mouse skin during aging. They proposed that DNA damage-induced COL17A1 proteolysis triggers transepidermal elimination of HFSCs, resulting in hair follicle shrinkage and hair loss.
    Previously, we have shown that CD34-positive HFSCs in mouse skin accumulate DNA-damage foci during physiological aging (independent of telomere shortening), leading to stem cell differentiation, but not to apoptosis or senescence (1). Chronic genomic stress associated with aging was imitated by exposing C57BL6 mice to daily low-dose irradiation (0.01 or 0.1 Gy) over several weeks, leading to gradual accumulation of persisting DNA-damage foci with rising cumulative doses (1, 2). Analyses of DNA-damage foci ultrastructure by electron microscopy combined with labeled DNA repair proteins suggested that aging-associated foci accumulation may not reflect persistently unrepaired DSBs, but chromatin rearrangements caused by repair or misrepair of DNA damage (1). Comparing residual chromatin alterations in HFSCs of aged versus irradiated skin, we observed that their ultrastructural dimensions reflect the complexity of the initial genotoxic insult (oxidative-stress-induced single-strand breaks during aging, double-strand breaks and more complex DNA lesions after irradiation), thereby explaining the various DNA damage responses, ultimately leading to different biological outcomes (1, 3). Matsumura et al. showed skin exposure to 10-Gy irra...

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    Competing Interests: None declared.
  • RE: Type XVII collagen expression shared across epithelial stem cell niches
    • Sumako Kameishi, Research fellow (Japan Society for the Promotion of Science), Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, Waseda University
    • Other Contributors:
      • Alessondra T Speidel, Research fellow, Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University
      • Takashi Kato, Professor, Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, Waseda University
      • Masayuki Yamato, Professor, Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University

    We read the excellent articles titled “Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis” (1) with great interest. These articles highlight the role of collagen type XVII in maintaining stemness and cell survival within the epithelial stem cell niche. We recently published a paper, “Characterization of rabbit limbal epithelial side population cells using RNA sequencing” (2), examining the well-known epithelial stem cell niche in the limbus, responsible for supporting corneal epithelial cell turn over. We FACS-sorted isolated limbal side population (SP) and non-SP (NSP) epithelial cells by ability to impair Hoechst 33342 efflux capability, performed transcriptome analyses of the sorted populations, and found differential expression in over 4,000 genes in SP cells. In this analysis, limbal epithelial SP cells demonstrated enriched expression of stem cell related genes. Interestingly, we found that both limbal epithelial SP and NSP cells express type XVII collagen and other proteins involved in its ECM structure. Further, limbal epithelial NSP cells express significantly higher levels of type XVII collagen and complementary ECM components, such as laminin alpha 3 and beta 3, major components of basement membrane under epithelia, compared with SP cells. This implies that limbal epithelial NSP cells may play a role in creating the corneal epithelial stem cell niche as well as bulge stem cells. Taken together, these findings suppor...

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    Competing Interests: None declared.