Study of hair follicles leads researchers to a key stem cell protein
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With all the excitement over what stem cells can become, a few basic questions tend to be overlooked: Where do they come from? And how do they survive? They are important questions, and the answer has relevance to potential stem cell therapies and to cancer. In a recent paper in Science, Rockefeller University’s Elaine Fuchs comes a step closer to addressing the issue, showing that in hair follicles, the protein Lhx2 acts as a molecular brake to regulate the switch between stem cell maintenance and activation.
“Scientists know that in adult skin, stem cells are found in an area called the hair follicle bulge,” says Horace Rhee, a graduate student in Fuchs’s lab and first author of the paper. “But what no one knew was how the stem cell compartment gets established during development, when the hair follicles are initially formed. The stem cells have to come from somewhere; the question is where?”
Using a special screening process, Rhee was able to isolate the cells in the skin just as they were first forming hair follicles. By comparing the genes expressed in those cells to those expressed in the surrounding cells, he hoped to identify genes that were important for early hair follicle specification.
“There are a lot of similarities between hair bud formation in embryonic skin and the activation of the adult hair follicle stem cells at the beginning of a new hair cycle,” says Fuchs. “This suggested to us that there may be similarities in their patterns of gene expression, which we found to be true.”
Many of the genes that were found in the screen were already known to be responsible for mouse and human hair disorders. One novel gene that Fuchs and Rhee found, called Lhx2, was one of the most strongly induced genes in the early hair bud. As the hair follicle developed, cells expressing Lhx2 became localized to the site of the future hair follicle, known as the bulge. By both overexpressing and repressing Lhx2 expression in the skin, and observing as the cells developed, Rhee and Fuchs saw that this protein indeed played an important role in stem cell specification and maintenance.
“When we overexpressed Lhx2 in the epidermis,” says Fuchs, “other genes associated with the follicle stem cells were also turned on. When we blocked Lhx2 expression in the follicle stem cells, we found that mice developed fewer hair follicles and a sparser hair coat.” Looking closer, the scientists found that the hair follicles deficient in Lhx2 had lost their ability to maintain stem cells.
“One of the most important discoveries of this study was that the origins of follicle stem cells could be traced from embryonic to adult skin,” says Fuchs, who is the Rebecca C. Lancefield Professor and head of the Laboratory of Mammalian Cell Biology and Development as well as an investigator at the Howard Hughes Medical Institute. “The identification of almost 100 new genes expressed in follicle stem cells and their daughter cells should be useful in further dissecting the process of how an epithelial bud structure forms, a process that likely has parallels in the formation of other tissues, such as mammary glands, lung epithelia and teeth.”
