Elaine Fuchs, Ph.D., talks with Steven Gabbe, M.D., after her recent Discovery Lecture. (photo by Mary Donaldson)
Lecturer probes mysteries of skin stem cells
Showing images of colorful animals and people, Elaine Fuchs, Ph.D., told the audience at last week's Discovery Lecture that “nature clearly has had a lot more fun and fancy in creating body surfaces than she has in creating any of the ugly organs that are tucked underneath.”
Fuchs, a Howard Hughes Medical Institute investigator at The Rockefeller University, detailed her laboratory's efforts over the last several years to characterize stem cells in the skin.
The outermost layer of skin, the epidermis, is like a cellophane wrapping on the body — it keeps essential fluids in and harmful microbes out. This wrapping repairs itself and is constantly renewed.
“Every four weeks, you've got a brand new epidermis, and if you're lucky throughout the course of your lifetime, your hairs not only undergo periods of rest, but also periods of growth,” Fuchs said.
“What all of these dynamic changes in equilibrium mean is that in the adult there have to be populations of stem cells to allow this continual rejuvenation of our body surface.”
Fuchs and her colleagues discovered that one population of skin stem cells resides in a region of the hair follicle known as the bulge, located just below the sebaceous glands. Each follicle, with its surrounding epidermis and associated sebaceous glands, has a stem-cell containing bulge region.
Fuchs' team devised a strategy for labeling the bulge stem cells with a green fluorescent protein, allowing the group to study the behavior of the cells in vivo and to use fluorescence-activated cell sorting technology to purify the cells and grow them in culture.
They observed that a few of the bulge cells were “activated” at the start of each hair cycle, and that many were activated in response to a wound at the skin surface. The investigators also grafted cultured bulge cells onto nude mice (mice that lack hair follicles) and observed tufts of hair at the graft.
“These results did give rise to a number of e-mails and phone calls from people, not necessarily scientists, who suddenly took a tremendous interest in our research,” Fuchs quipped.
The hair, coming from cells labeled with green fluorescent protein, glowed green, as did the associated skin and sebaceous glands, demonstrating that the stem cells existing within the bulge are “multipotent stem cells” — stem cells capable of giving rise to multiple different types of differentiated tissues, Fuchs said.
Using microarray analysis, the group has profiled gene expression patterns in the bulge stem cells, finding more than 150 genes that are preferentially expressed in the stem cells. Both TGF-beta and BMP signaling pathways are active in the bulge cells, Fuchs said.
The team recently demonstrated that the multipotent skin stem cells can be used to clone mice — the first study to successfully clone healthy mice from any type of adult stem cell.
“We hope that we're starting to get a link between understanding normal tissue morphogenesis, transient repair and wound response, and then what goes wrong when this machinery becomes mutated,” Fuchs said.
“We think there's going to be a very strong link … in understanding transitions to cancer.”
Fuchs' lecture was the first in the Lloyd E. King Jr. lectureship, launched this year to honor King's long-term dedication to building dermatology at Vanderbilt. King, M.D., Ph.D., professor of Medicine, served as chief of the Division of Dermatology for 25 years.
For a complete schedule of the Discovery Lecture Series and archived video of previous lectures, go to www.mc.vanderbilt.edu/discoveryseries.