Female Skin Stem Cells Show Synchronized Renewal While Healing Faster Than Male Skin
Female mice regenerate skin wounds faster than males due to fundamental biological differences in how skin stem cells behave, according to a study published in Nature. Researchers observed skin stem cells in living mice over a five-month period and found that female cells operate in a synchronized manner, whereas male cells act independently. These distinct cellular patterns are governed by sex hormones.
University Teams Track Stem Cells Over Five Months
Under the direction of Prof. Cédric Blanpain—who serves as a WEL Research Institute investigator, heads the Laboratory of Stem Cells and Cancer, and teaches at the Université libre de Bruxelles (ULB)—the team employed sophisticated microscopy to film single cells directly through the skin of live mice. The study was conducted in collaboration with Prof. Benjamin Simons and his team at the University of Cambridge, alongside research groups led by Michele De Luca at the University of Modena and Reggio Emilia, Yulia Shwartz at the Broad CIRM Center at the University of Southern California, and Esther Hoste at VIB-Ghent University.
The observation period spanned five months, allowing scientists to track stem cells and their descendants continuously. The team discovered that stem cells pass through an intermediate stage with limited division capacity before maturing into specialized cells that form the protective outer barrier of the skin. During this process, sister cells in female mice frequently execute identical developmental decisions simultaneously, mirroring how two rowers move oars in unison. Male sister cells display less synchronization and follow independent patterns.
We initially set out to understand how the skin renews itself, and whether there is a hierarchy with stem cells at the top. We were surprised to discover strong differences in the way stem cells renew the skin in females and males,
explains Doctor Dan Engelman, the first author of the study.
Sex Hormones Direct Cellular Maturation and Proliferation
Controlled experiments revealed that sex hormones dictate these divergent behaviors. Castration of male mice removed testosterone, causing their skin cells to adopt female-like behavior. Subsequent administration of dihydrotestosterone (DHT) restored the typical male pattern by regulating the speed at which skin cells mature and migrate out of the stem cell layer.
Conversely, removing the ovaries of female mice reduced stem cell multiplication rates and eliminated cellular synchronization. Estradiol treatment reversed this reduction. Laboratory tests on reconstructed human skin showed that testosterone similarly accelerated stem cell differentiation, indicating that portions of the mechanism observed in rodents operate in humans as well.
Wounds on the backs of female mice closed substantially faster during the initial days following injury. This advantage stems from skin stem cells activating sooner and functioning with greater coordination, though the performance gap narrows as healing progresses.
This study is a technological tour de force, and the discovery of differences between male and female skin stem cells is fascinating and entirely unexpected,
Prof. Blanpain states. It sheds light on a series of clinical observations that previously lacked a biological explanation.
The findings offer potential pathways for improving recovery outcomes from surgical procedures and severe burns, alongside developing treatments for chronic wounds in diabetic patients. Financial backing for the research was supplied by the European Research Council (ERC), the joint FNRS/FWO EOS Excellence of Science program, the Fonds Yvonne Boël, the Fondation Julie et Françoise Drion, the Fonds Erasme, the Fondation ULB, the Fondation contre le Cancer, the WEL Research Institute, TELEVIE, and the FNRS through FRIA fellowships.
Frequently Asked Questions About Sex Differences in Skin Renewal
How long did researchers observe the skin stem cells in the study?
Scientists tracked individual cells through the skin of living mice for five months using advanced microscopy techniques.
Which academic institutions collaborated on the research published in Nature?
The project brought together teams from the Université libre de Bruxelles, the University of Cambridge, the University of Modena and Reggio Emilia, the University of Southern California, and VIB-Ghent University.
What specific hormone treatments reversed the cellular changes in the experiments?
Administering dihydrotestosterone restored male cell patterns after castration, while estradiol treatment reversed the drop in stem cell proliferation caused by the removal of ovaries in female mice.
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