Genetic mechanisms in the follicular niche behind balding and gray hair identified.
Genetic mechanisms in the follicular niche behind balding and gray hair identified.

Scientists have not only identified the cells that directly give rise to hair, they have also revealed the mechanism within these cells that causes hair to turn gray. To reach these findings, the scientists had to peer deeply into the follicular niche, a murky place where stem cells, progenitor cells, and melanocytes do whatever it is they do to produce richly pigmented hair—or not.

What ultimately turned into an exploration of the hair matrix actually began as a cancer research project at UT Southwestern Medical Center. Specifically, the scientists were studying a disorder called neurofibromatosis type 1, a rare genetic disease that causes tumors to grow on nerves.

“Although this project was started in an effort to understand how certain kinds of tumors form,” noted Lu Le, M.D., Ph.D., “we ended up learning why hair turns gray and discovering the identity of the cell that directly gives rise to hair.”

“With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.”

Details of the research appeared May 2 in the journal Genes & Development, in an article entitled “Identification of Hair Shaft Progenitors That Create a Niche for Hair Pigmentation.” According to this article, the UT Southwestern team sought to better understand the identities of progenitor cells in the matrix and the mechanisms by which they regulate hair shaft components.

“We report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20,” wrote the article’s authors. “Depletion of Krox20 lineage cells results in arrest of hair growth, confirming the critical role of KROX20+ cells as antecedents of structural cells found in hair.”

Essentially, the researchers found in skin cells that become the hair shaft, KROX20, a protein more commonly associated with nerve development, is expressed. These hair precursor, or progenitor, cells then produce a protein called stem cell factor (SCF).

“Expression of SCF by these cells is necessary for the maintenance of differentiated melanocytes and for hair pigmentation,” the researchers added.

When the SCF gene in the hair progenitor cells was deleted in mouse models, the animal's hair turned white. When the KROX20-producing cells were depleted, no hair grew and the mice became bald.

Scientists already knew that stem cells contained in a bulge area of hair follicles are involved in making hair and that SCF is important for pigmented cells, said Dr. Le. What they did not know in detail is what happens after those stem cells move down to the base, or bulb, of hair follicles and which cells in the hair follicles produce SCF—or that cells involved in hair shaft creation make the KROX20 protein, he said.

If cells with functioning KROX20 and SCF are present, they move up from the bulb, interact with pigment-producing melanocyte cells, and grow into pigmented hairs.

“Our findings,” the authors of the Genes & Development article concluded, “reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes.”

UT Southwestern researchers will now try to find out if the KROX20 in cells and the SCF gene stop working properly as people age, leading to the graying and hair thinning seen in older people—as well as in male pattern baldness, Dr. Le indicated

The research also could provide answers about why we age in general, as hair graying and hair loss are among the first signs of aging.

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