Hair follicles provide the stem cells for the skin's entire epidermis

August 16, 2000

The hair follicle isn't just a hair factory. Researchers have now discovered that the hair follicle is the source of new cells for the skin's outermost layer, the epidermis, which is replenished throughout life. And these cells, according to a new study by researchers at New York University School of Medicine and the University of Pennsylvania School of Medicine, reside in a well-protected area of the follicle, called the "bulge," that lies just underneath the skin.

The new study, led by Tung-Tien Sun, Ph.D., of NYU School of Medicine, and Robert Lavker, Ph.D., of the University of Pennsylvania School of Medicine, is published in the August 18 issue of the journal Cell. Using a novel double-labeling system, the researchers were able to track the path of the progeny of stem cells as they traveled from the bulge into the epidermis of mice, where they settled in as epithelial cells. Epithelial stem cells are primitive progenitor cells that supply the cells needed for replenishing the skin, one of the body's self-renewing tissues. (These cells aren't related to the stem cells found in the bone marrow.)

"We used to think that the hair follicle had its own stem cells, and that the epidermis had its own stem cells," says Dr. Sun, who is the Rudolf L. Baer Professor of Dermatology and Professor of Pharmacology and Urology at NYU School of Medicine. "Now we believe that there aren't two separate entities. Instead, there is only one entity, an ultimate epidermal stem cell that is capable of forming skin or hair." (Despite the great difference in their appearance, hair and skin are closely allied. Hair is composed of a protein called keratin, a specialized product of epithelial cells.)

"This is an important new concept," says Dr. Lavker, Professor of Dermatology, at the University of Pennsylvania School of Medicine. "Our findings suggest that certain types of skin cancer probably arise from epidermal stem cells found in the bulge, because these cells and their progeny are located near the skin's surface within easy reach of chemical carcinogens. And this new concept may also provide new therapeutic approaches to a variety of epidermal skin diseases, such as psoriasis, which may involve epithelial stem cells."

In the new study, the researchers figured out how to identify the stem cells in the bulge by tagging them with two chemicals. One bestows a red glow to the nuclei of these cells, and the other emits a specific radioactive signature. The technique relies on the fact that these stem cells take a relatively long time to go through the cell cycle, the process by which a cell divides. In a series of experiments involving three-day-old mice and adult mice, the researchers found that after a certain amount of time, the labeled cells had decreased in the upper follicle and increased dramatically in the epidermis.

Dr. Sun and Dr. Lavker have enjoyed a working partnership that extends over two decades. They are especially known for their discoveries of stem cells residing in various organs of the body. In the 1980s, for example, they found that the stem cells for the cornea resided in an area called the limbus on the cornea's periphery. The discovery led to a new surgical technique called "limbal stem-cell transplantation," in which a piece of the limbus from the patient's good eye or from that of a related donor is used to restore eye sight in patients suffering severe corneal damage.

In 1990 Dr. Sun and Dr. Lavker made another stem-cell discovery. Researchers had assumed that the hair's stem cells lurked in the bottom of the follicle in a structure called the "bulb." But Dr. Sun and Dr. Lavker found the stem cells in the bulge, which is located in the upper part of the hair follicle. The discovery changed the understanding of hair growth. In the new scenario, stem cells migrate to the bulb, where they interact with a region called the "dermal papilla," to promote hair growth. Hence, "hair grows down and then grows up," says Dr. Sun.

Human skin is continually renewed throughout life, and 90% of the body is covered by hair. However, there are no hair follicles in the palms, the soles of the feet, and the foreskin of the penis. Dr. Sun and Dr. Lavker reported nearly twenty years ago that the epithelial stem cells that supply new cells to these areas are located in an undulating, lower region of the epidermis.
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NYU Langone Medical Center / New York University School of Medicine

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