Skin Stem Cells in Silence, Action, and Cancer

Abstract

In studying how stem cells make and maintain tissues, nearly every chapter of a cell biology textbook takes on special interest. The field even allows us to venture where no chapters have yet been written. In studying this basic problem, we are continually bombarded by nature's surprises and challenges. Stem cell biology has captured my interest for nearly my entire scientific career. Below, I focus on my laboratory's contributions to this fascinating field, to which so many friends and colleagues have made seminal discoveries equally deserving of this award.

Keywords: cancer; epidermis; hair follicle; skin; stem cells; wound healing.

Figure 1

Early Stages of Stem Cell Activation in Two Hair Follicles The stem cells that fuel the hair cycle are located within the outermost layer of the bulge niche. At the base of this niche (hair germ) are “primed” stem cells. These stem cells become activated at the start of each new hair cycle to form TGF-β-signaling progenitors that progress to produce the hair shaft and its channel. Several days later, the bulge stem cells begin to proliferate to self-renew and fuel the outer root sheath production that pushes the signaling center with the dermal papilla away from the bulge, returning the bulge to quiescence. Note that other cells within the skin have been removed for the purposes of illustration here, and that the image has been pseudocolored to highlight the mesenchymal stimulus (dermal papilla): Cyan marks nuclei of dermal papilla; red, pSmad2 denotes proliferative progeny that emerged from the base of the bulge stem cell niche at the start of the hair cycle. Green denotes Ki67, a marker of cycling cells. The image was prepared by Naoki Oshimori, when he was a postdoctoral fellow in my laboratory.

Elaine Fuchs received her undergraduate degree in Physical Chemistry from The University of Illinois, where she graduated with the highest distinction. She went on to earn her DPhil in Biochemistry from Princeton University. As a Damon Runyon postdoctoral fellow under the tutelage of Professor Howard Green, Elaine began to tackle the molecular biology of epidermal stem cells as a tool to understand how tissues balance growth and differentiation. Elaine’s early studies on the faculty at the University of Chicago culminated in several landmark papers in Cell in which she pioneered reverse genetics, starting with biochemical and molecular dissection of the stem cell’s structural proteins, keratins, and then turning to mice and final human patients to guide her to the basis of blistering skin disorders. Elaine’s group has gone on to elucidate how epidermal stem cells utilize cellular and cytoskeletal interactions to generate and replenish the skin’s barrier. Upon her move to Rockefeller University in 2002, Elaine began to focus on other skin stem cells, including those of the hair follicle and sweat glands, to illuminate how these very different tissue structures are generated and replenished. Her current interests are in the realm of how stem cells cope with stress, from wound repair to inflammation to cancer. Elaine is a Howard Hughes Medical Institute Investigator, an elected member of the National Academy of Sciences, National Academy of Medicine and the American Philosophical Society. She has received numerous awards, including the United States’ highest scientific honor, the National Medal of Science from President Obama, the Albany Prize in Medicine, the L’Oreal-UNESCO Women in Science Award, the EB Wilson Award in Cell Biology, the International Pezcoller Award for Cancer Research and the McEwen Award for Innovation in Stem Cell Research. She has also received honorary doctorates, most recently from Harvard University.