ULB and Cambridge film skin stem cells in mice for five months: renewal differs by sex

Researchers at the Université libre de Bruxelles (ULB), working with the University of Cambridge, filmed skin stem cells in living mice for five months. They found that in females these cells renew the skin in a more coordinated way than in males, according to eurekalert.org eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗. The difference is controlled by sex hormones and goes together with faster wound healing in female mice. The study was published in Nature and led by Prof. Cédric Blanpain of ULB, with the team of Prof. Benjamin Simons at Cambridge and other partner institutions.

The team used a microscopy technique that allows cells to be filmed through the skin of a living animal. This let them follow the same stem cells and their descendants for five months, a tracking period the authors describe as unprecedented.

How the skin renews itself

The outer layer of the skin is constantly renewed. Stem cells at the bottom multiply. Some daughter cells remain stem cells, while others differentiate into specialized cells that form the skin barrier, cannot divide, move to the surface and are shed. Filming the same areas showed that stem cells do not turn directly into mature skin cells. They first pass through an intermediate stage in which they can divide only a limited number of times.

In females, two sister cells born from the division of the same cell tend to make the same choice at the same time: divide again or specialize. The authors compare this to rowers synchronizing their strokes. In males, each cell follows its own rhythm to a greater extent eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.

Role of sex hormones

Castration of male mice, which removes the main source of testosterone, made male skin behave more like female skin. Treatment with dihydrotestosterone (DHT), an active form of testosterone, restored the male behaviour. Removal of the ovaries in females reduced stem cell proliferation, an effect reversed by oestradiol, and almost abolished the coordination between sister cells. According to the authors, testosterone controls the rate of skin cell maturation, while oestrogens drive stem cell proliferation and contribute to their coordination.

In human skin reconstructed in the laboratory, testosterone also accelerated stem cell differentiation, which the authors say suggests that the mechanism exists in humans. A wound on the back closed markedly faster in female mice, especially in the first days. This is partly explained by earlier and more coordinated activation of stem cells, and the gap narrows as the wound closes.

The authors say the work could eventually inform treatments that take the patient's sex into account. The team plans to study male–female differences in the formation and progression of skin cancers, as well as the molecular mechanisms behind them eurekalert.orgeurekalert.orgeurekalert.orgOpen source ↗.