A new look at sebaceous glands offers insight into the development and maintenance of the skin and how cancer mutations affect stem cell behavior.
Most people are familiar with the sebaceous glands which are responsible for moisturizing the skin—during puberty sometimes more than we would like. But even though the glands are a main component of our skin, scientists know surprisingly little about their formation and maintenance.
“We demonstrate for the first time ever how the sebaceous glands that contribute to the natural moisture of the skin are formed and how they are maintained throughout life by stem cells. This knowledge may be transferred to individuals with sebaceous gland conditions, e.g. acne or very dry skin,” says postdoctoral researcher Marianne Stemann Andersen from the Biotech Research & Innovation Centre (BRIC) at the University of Copenhagen.
The study also shows that the behavior of the stem cells changes when the researchers introduce a specific and frequently found cancer mutation to the skin stem cells. Surprisingly, the mutation did not as expected cause cells to divide more often; instead stem cells had a tendency to generate more stem cells and not mature sebaceous gland cells when they divided.
“In this case, the result is a sebaceous gland which—similar to tumors—continues to grow. We hope this knowledge can contribute to the design of better cancer treatment,” says associate professor and head of the study Kim Jensen from BRIC and the Novo Nordisk Foundation Center for Stem Cell Biology (DanStem).
In the study, the researchers tracked stem cell division in the skin of live mice and colored individual stem cells with fluorescent proteins. This let the researchers follow stem cells during a number of cell divisions and essentially generate family trees describing the heritage of individual cells.
During the formation of the sebaceous gland, the researchers found that when a stem cell divided and gave rise to two daughter cells, this more often led to the formation of two new stem cells than into mature sebaceous gland cells. This way, the sebaceous gland continued to grow until it had reached its mature size. At this point the behavior of the stem cells changed: New cells only emerged when mature sebaceous gland cells burst to release their moisturizing lipids on the skin and thereby be lost from the sebaceous gland.
In mice where the researchers introduced a specific mutation often found in human cancers into stem cells of the sebaceous gland this behavior changed dramatically. Here even in adult mice the sebaceous gland continued to grow.
“We used to believe that this mutation led to more frequent cell divisions. However, our research shows that its effect on how often cells divide is very mild. Instead, stem cells with the cancer mutation are much more likely to divide into two new stem cells than generating mature sebaceous gland cells. This explains why the sebaceous gland continues to grow after we introduce this mutation to the skin,” says postdoctoral researcher Svetlana Ulyanchenko of BRIC.
“In connection with cancer therapies that target cells that divide frequently, this means that cancer cells and normal cells are just as likely to be targets of the treatments. If we are able to determine what controls how often cells divide when mutated, we may be able to develop therapies that specifically affect cancer cells.”
In the future, Jensen’s research team wants to expand its analysis to other cancer mutations and study how different mutations in the same cell interplay and change stem cell behavior. According to the researchers, such studies would offer a main basis for far more effective cancer treatment.
The work appears in Nature Cell Biology. The study is the result of collaboration with the University of Cambridge and Université Cote d’Azur in Nice, France. First authors of the study are Andersen, Edouard Hannezo, and Ulyanchenko.
Funding came from the Lundbeck Foundation, the Novo Nordisk Foundation, the LEO Foundation, the EMBO Young Investigator program, the EU Horizon 2020 program, and the European Research Council, among others.
Source: University of Copenhagen