Keratinocyte stem cells are more resistant to UVA radiation than their direct progeny

PLoS One. 2018 Sep 12;13(9):e0203863. doi: 10.1371/journal.pone.0203863. eCollection 2018.

Abstract

The epidermis undergoes constant renewal during its lifetime. This is possible due to a special population of keratinocyte stem cells (KSCs) located at the basal layer. These cells are surrounded by their direct progeny, keratinocyte progenitors or transient amplifying cells (TAs), which arise from cell division. Skin is exposed every day to sun radiation; in particular, UVA radiation penetrates through the epidermis and induces damage to KSCs and TAs. Although keratinocytes in the basal layer are the most likely skin carcinomas and/or photoaging cells of origin, surprisingly few studies have addressed the specific responses of these cells to UV radiation. In this study, we showed for the first time that keratinocyte stem cells were more resistant to UVA irradiation than their direct progeny, transient amplifying cells. Using both the MTT assay and clonogenic assay, we found that KSCs were more photo-resistant compared to TAs after exposure to different doses of UVA (from 0 to 50 J/cm2). Moreover, KSCs had a greater ability to reconstruct human epidermis (RHE) after UVA exposure compared with TAs. Finally, investigations of DNA repair using the comet assay showed that DNA single-strand breaks and thymine dimers were repaired quicker and more efficiently in KSCs compared with TAs. In a previous work, we showed that the same stem cell population was more resistant to ionizing radiation, another carcinogenic agent. Collectively, our results combined with other observations demonstrate that keratinocyte stem cells, which are responsible for epidermal renewal throughout life, are equipped with an efficient arsenal against several genotoxic agents. Our future work will try to identify the factors or signaling pathways that are responsible for this differential photo-sensitivity and DNA repair capacity between KSCs and TAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Differentiation / radiation effects
  • Comet Assay
  • DNA Breaks, Single-Stranded / radiation effects
  • DNA Damage / genetics
  • DNA Repair / genetics
  • Dermis / radiation effects
  • Epidermal Cells / radiation effects
  • Epidermis / metabolism
  • Epidermis / radiation effects
  • Female
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / radiation effects*
  • Primary Cell Culture
  • Pyrimidine Dimers / metabolism
  • Radiation Tolerance / genetics
  • Skin / radiation effects
  • Stem Cells / metabolism
  • Stem Cells / radiation effects*
  • Ultraviolet Rays / adverse effects

Substances

  • Pyrimidine Dimers

Grants and funding

This work was supported in part by Gattefossé Company. Elodie Metral was supported by a grant from Gattefossé. Nicolas Bechetoille and Frédéric Demarne are employees of Gattefosse. E.M, N.B and F.D. are employees of Gattefosse. O.D. is hospital practitioner at Civil Hospitals of Lyon. W.R. is Prof. at University Grenoble Alpes. The financial support from Gattefosse does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials and there are no restrictions on sharing of data and/or materials. E.M.: performed research, analyzed data, and wrote the paper. N.B. and F.D wrote and review the paper. O.D and W.R designed and supervise research, analyzed data, and wrote the paper. The financial support from Gattefosse does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials and there are no restrictions on sharing of data and/or materials.