Sweat glands control our body temperatures, but little is known about how they develop and the cells that give rise to them. However, researchers from Rockefeller University have now identified in mice the stem cell population from which sweat glands originally develop and the stem cells that regenerate adult sweat glands.
In this study, scientists from the laboratory of Elaine Fuchs invented a strategy to purify and molecularly characterize the different kinds of stem cell populations that make up the complex sweat duct and glands found in mammalian skin. Afterwards, they examined how these different stem cell populations respond to normal tissue homeostasis and to different types of skin injuries. They also found how sweat glands differ from their close cousins, the mammary glands.
Elaine Fuchs, who is an investigator at the Howard Hughes Medical Institute, said: “Mammary gland stem cells respond to hormonal induction by greatly expanding glandular tissue to increase milk production. In contrast, during a marathon race, sweat gland stem cells remain largely dormant,and glandular output rather than tissue expansion accounts for the 3 liters of sweat our body needs. These fascinating differences in stem cell activity and tissue production are likely at the root why breast cancers are so frequent, while sweat gland cancers are rare.”
These findings from Fuchs’ lab might someday help improve treatment strategies for burn patients and to develop topical treatments for people who sweat too much, or too little.
“For now, the study represents a baby step towards these clinical goals, but a giant leap forward in our understanding of sweat glands,” said the study’s lead author, Catherine P. Lu, a postdoctoral researcher in Fuchs’s laboratory.
Each one of us has millions of sweat glands but they have rarely been extensively studied, and much of this has to do with the difficulty of gathering enough of the tiny organs to research in a lab. Mice are traditionally used as a model for human sweat gland studies. Therefore, for this study, Lu and colleagues laboriously extracted sweat glands from the tiny paw pads of mice, the only place they are found in these and most other mammals. The goal was to determine if the different cells that make up the sweat gland and duct contained stem (progenitor) cells that can repair damaged adult glands.
According to Lu, “We didn’t know if sweat stem cells exist at all, and if they do, where they are and how they behave.” The last major studies on the proliferative potential within sweat glands and sweat ducts were conducted in the early 1950s before modern biomedical techniques were used to understand fundamental biomedical science.
Fuchs’ team determined that just before birth, the nascent sweat duct forms as a down-growth from progenitor cells in the epidermis, the same master cells that at different body sites give rise to mammary glands, hair follicles and many other epithelial appendages. As each duct grows deeper into the skin, a sweat gland emerges from its base.
Lu then led the effort to look for stem cells in the adult sweat gland. Sweat glands are composed of two layers: an inner layer of luminal cells that produce the sweat and an outer layer of myoepithelial cells that squeeze the duct to discharge the sweat.
Lu devised a strategy to fluorescently tag and sort the different populations of ductal and glandular cells. The Fuchs team then injected each population of purified cells into different body areas of female host recipient mice to see what the cells would do.
When introduced into the mammary fat pads, the sweat gland myoepithelial cells generated fluorescent sweat gland-like structures. “Each fluorescent gland had the proper polarized distribution of myoepithelial and luminal cells, and they also produced sodium-potassium channel proteins that are normally expressed in adult sweat glands but not mammary glands,” Lu said.
When the host mice became pregnant, some of the fluorescent sweat glands began to express milk, even though they still retained some sweat gland features as well. Sweat gland myoepithelial cells produced epidermis when engrafted to the back skin of the mice.
“Taken together, these findings tell us that adult glandular stem cells have certain intrinsic features that enable them to remember who they are in some environments, but adopt new identities in other environments,” Fuchs said. “To test the possible clinical implications of our findings, we would need to determine how long these foreign tissues made by the stem cells will last, unless it is long-term, a short-term “fix” might only be useful as a temporary bandage for regenerative medicine purposes,” Fuchs said.
The findings can now be used to explore the roots of some genetic disorders that affect sweat glands, as well as ways to potential ways to treat them.
“We have just laid down some critical fundamentals of sweat gland and sweat duct biology,” Lu said. “Our study not only illustrates how sweat glands develop and how their cells respond to injury, but also identifies the stem cells within the sweat glands and sweat ducts and begins to explore their potential for making tissues for the first time.”