Researchers at the ULB (Free University of Brussels ) are discovering new properties of adult stem cells in response to DNA damage. These findings have major implications for understanding the carcinogenesis and aging mechanisms.

Adult stem cells are the basis for regeneration and tissue repair, providing new cells to replace cells that are damaged or dead. As stem cells stay in tissues for long periods of time, they create a significant risk of accumulating mutations that may lead to the development of cancer or aging. Little is known about the way stem cells perceive and respond to damage to their DNA.

Panagiota Sotiropoulou and Aurelie Candi, two researchers from the group of Cedric Blanpain, IRIBHM, ULB, have defined the functional consequences and molecular mechanisms by which hair follicle stem cells respond to DNA damage in vivo. They have demonstrated that adult stem cells from the skin are extremely resistant to DNA damage-induced cell death (Apoptosis).

Researchers have dissected the molecular mechanisms at the basis of this new feature of adult stem cells as a result of using a variety of techniques, including biochemical and transcriptional characterisation of stem cells before and after exposure to DNA damage. They have demonstrated that two major molecular mechanisms contribute to the higher resistance of the hair follicle stem cells to DNA damage-induced cell death. The hair follicle stem cells express the anti-apoptotic protein Bcl-2 at a higher level, thus countering the effects of genes stimulating DNA damage-induced cell death.

The second mechanism for the hair follicle stem cells' increased resistance to DNA damage is linked to the temporal activation of the “genome caretaker” called p53. The activation of p53, which triggers off programmed cell death when DNA damage is too extensive, is much shorter in the hair follicle stem cells. Researchers have found that the more transient activity of p53 is correlated with a much faster DNA repair in the hair follicle stem cells. Mice that are deficient in DNA repair have a p53 expression that lasts longer, resulting in increased cell death in the hair follicle stem cells following damage to their DNA.

The study findings show that resistance to DNA damage and faster DNA repair represent two new characteristics of adult stem cells. Further studies are needed to determine how far these characteristics represent a general mechanism shared by different types of adult stem cells. These findings also show that follicle stem cells repair their genome using a DNA repair mechanism known to induce errors during the repair process, which may therefore lead to a long-term accumulation of mutations in stem cells. This suggests that the mechanism could be a double-edged sword for adult stem cells, encouraging the short-term survival of stem cells after exposure to DNA damage at the expense of maintaining genomic integrity in the long term. “In terms of evolution, this protective mechanism of stem cells has huge significance. Hundreds of years ago, aging and cancer were not a matter of survival for human beings, whose life expectancy did not exceed 30 years. It was more important to protect stem cells from cell death than prevent new mutations in their genomes, “says Panagiota Sotiropoulou, the lead author of the study. These findings have major implications for understanding the sensitivity of certain tissues to DNA damage-induced carcinogenesis and aging.