Skin cells reveal they have hairy origins.

About every 2 weeks, people literally shed their skin. That's how long it takes for the outer layers, also known as the epidermis, to turn over. Dead cells on top slough off, exposing younger cells below.

The ultimate source of fresh skin may not be the skin itself. According to one group of biologists, hair follicles are the natural birthplaces of skin cells.

"There may be a very slow and very steady trafficking of cells, in the normal adult, from hair follicles to the epidermis," contends Robert M. Lavker of the University of Pennsylvania School of Medicine in Philadelphia. In the Aug. 18 CELL, a team led by Lavker and his longtime collaborator Tung-Tien Sun of the New York University School of Medicine offers evidence supporting this hypothesis.

The two investigators specialize in teasing out the origins of tissues. In the past, they identified the eye's reservoir of unspecialized cells, so-called stem cells, that replenish corneal tissue. A decade ago, Lavker and Sun proposed that a small bulge about halfway up the side of hair follicles harbors stem cells that could give rise to the specialized cells of both the hair follicle and the surrounding epidermis.

That cells from hair follicles can produce skin under extreme circumstances is well known. In people with third-degree burns, for example, any regenerating skin appears as a growing island with a hair follicle at its center.

In their recent work, Lavker and Sun labeled cells in mouse hair follicles so they could follow the fate of those cells. When they marked bulge cells in the hair follicles of newborn mice, the investigators found that some offspring of these cells migrated downward to form the lower part of the follicles.

In an attempt to see where skin arises in newborn mice, the scientists tagged progeny of bulge cells that had moved into the upper portion of follicles and followed their fate. "All of a sudden we found [these labeled] cells appearing in the epidermis. They couldn't have come from anywhere other than migration up the follicle," says Lavker.

To discern where new skin comes from during wound repair, the scientists created a small wound on the backs of mice and injected the animals with the markers that label cells in the upper follicles. Over time, the number of labeled cells in the injured epidermal areas rose, while the tally of such cells in the upper follicles fell. This implies that follicular cells play a crucial role in normal skin repair, says Lavker.

It'll be tricky to prove bulge cells are the key to the skin's natural ability to turn over in the adults. Epidermal cells proliferate so readily that normally there may not be a need for a large flow of stem cells up from the bulge to the skin, Lavker notes.

Some researchers point out that several areas of skin, such as the palms, contain no hair follicles at all. That leads them to suspect that there's a population of skin stem cells residing in a lower layer of the epidermis.

"That the hair follicles serve as a source of epidermal cells does not rule out the possibility that there is a resident stem cell in the epidermis as well. Both camps are probably correct," says Kurt Stenn, director of skin biology at the R.W. Johnson Pharmaceutical Research Institute in Skillman, N.J.

Lavker and Sun plan to continue studying hair follicle cells, in part to explain why laboratory-induced skin tumors in mice usually seem to originate in the upper follicle but not the bulge itself.