Wound healing: the stem cell dynamics

One of the key questions in biology is to identify how tissues are repaired after trauma and understand how stem cells migrate, proliferate, and differentiate to repair tissue damage. We identified the cellular and molecular mechanisms that regulate wound healing in the skin.

HFSP Long-Term Fellow Mariaceleste Aragona and colleagues
authored on Tue, 07 March 2017

The skin epidermis is the first barrier protecting animals against the external environment. When the skin barrier is disrupted, a cascade of cellular and molecular events is activated to repair the damage and restore skin integrity. Defects in these events can lead to improper repair causing acute and chronic wound disorders. In the epidermis, distinct stem cell populations contribute to wound healing. However, it remains unclear how these different stem cell populations balance proliferation, differentiation and migration during the healing process.  In this newly published study, we define the clonal dynamics and the molecular mechanisms that lead to tissue repair in the skin epidermis.

Figure: 3D rendering of a clone (in red) originating from a basal epidermal stem cell. The cells are proliferating and moving towards the direction of the wound (on the right). (Credit: Mariaceleste Aragona, Sophie Dekoninck and Cedric Blanpain)

Using state of the art genetic mouse models to trace different stem cells populations, we mark stem cells and follow the fate of their progeny over time. Interestingly, we found that stem cells coming from different epidermal compartments present a very similar response during wound repair, despite the fact that they are recruited from different regions of the epidermis.  We provide the molecular profiling of different regions surrounding the wound to uncover the gene expression signature of the cells that actively divide and those that migrate to repair the wound. The data suggests that the migrating leading edge cells are protecting the stem cells from the infection and mechanical stress allowing a harmonious healing process.

Altogether, this study provides important insights into the changes in the mechanisms that lead to tissue repair, demonstrating that the capacity of the stem cells to regenerate a tissue does not depend on their cellular origin but rather on their proliferation capacity, and identifies new molecular players associated with skin regeneration.

For the full story see the press release from the Université Libre de Bruxelles. 

Reference

Defining stem cell dynamics and migration during wound healing in mouse skin epidermis. Aragona M, Dekoninck S, Rulands S, Lenglez S, Mascré G, Simons BD, Blanpain C. Nature Communications (2017) doi:10.1038/ncomms14684.

Link to article

Pubmed link

Link to Blanpain lab website