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Sensing radiosensitivity of human epidermal stem cells.

Walid Rachidi1, Ghida Harfourche, Gilles Lemaitre

  • 1Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse, CEA, IRCM, Envy, France.

Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology
|June 2, 2007
PubMed
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Human epidermal stem cells are radioresistant, unlike their progenitor cells. This radioresistance is linked to distinct DNA damage signaling pathways, including repressed apoptosis and induced cytokine networks, offering new insights into radiation response in skin stem cells.

Area of Science:

  • Dermatology and Radiation Biology
  • Stem Cell Biology
  • Molecular Oncology

Background:

  • The radiosensitivity of stem cells is a complex and debated topic, with varying reports for mouse somatic stem cells.
  • Human stem cell responses to radiation remain largely understudied, despite the epidermis being a radiosensitive tissue.

Purpose of the Study:

  • To evaluate the radiosensitivity of human epidermal stem cell populations.
  • To investigate the differential response of human epidermal stem cells and progenitors to ionizing radiation.

Main Methods:

  • Isolation of total keratinocytes from human skin, followed by flow cytometry to enrich for basal cell populations.
  • Assessment of cell survival using XTT and clonogenic assays post-2Gy irradiation.
  • Transcriptome analysis via oligonucleotide microarrays to determine genomic responses to radiation.

Related Experiment Videos

Main Results:

  • Human epidermal stem cells, isolated using alpha6 integrin and CD71 markers, demonstrated radioresistance.
  • Progenitor cells exhibited radiosensitivity, confirmed by both XTT and clonogenic assays.
  • Stem cells showed a significantly reduced gene expression response to radiation (6% regulated genes) compared to progenitors (20% regulated genes).
  • Irradiated stem cells displayed repressed apoptosis-related gene networks and induced cytokine/growth factor networks.

Conclusions:

  • Human epidermal stem cell populations enriched for stem cells are radioresistant.
  • The primary radiation response in these stem cells involves the regulation of genes related to cell death, survival, and apoptosis.
  • These findings provide novel insights into the distinct radiobiological mechanisms of human epidermal stem cells versus progenitors.