Until now hair, apart from being aesthetically pleasing, was thought to have served no real purpose. However, new research from Rockefeller University reveals that a structure at the base of each strand of hair, the hair follicle, uses a two-step mechanism to activate its stem cells and order them to divide. This discovery will provide insights into how repositories of stem cells may be organised in other body tissues for the purpose of supporting organ regeneration.
“The hair follicle is like a mini-dispensable organ,” said Elaine Fuchs, head of the Laboratory of Mammalian Cell Biology and Development. “Throughout our lifetime, each hair follicle undergoes cyclical bouts of growth, destruction and rest through an intrinsic stem cell population. It provides an excellent opportunity to investigate the molecular process of tissue regeneration and stem cell self-renewal.”
In their work, Fuchs and her team scrutinized the hair cycle through the resting phase. Each hair follicle goes through a hair growth lifecycle of anagen (growth), catagen (regression), and telogen (resting), then back to anagen. For a new round of hair growth to begin, stem cells in the hair follicle must receive a signal to divide. In response to this signal, the hair follicle regenerates first by growing downward through the skin’s middle layer, the dermis, and then producing the specialised cells that form the hair. After this growth period, the stem cells stop dividing and the hair follicle gradually retracts again.
Fuchs and her team discovered that during most of the telogen (resting) phase, both the bulge (the base of the hair follicle) and the hair germ (a smaller cluster of cells at the very bottom of the bulge) remain dormant. By isolating cells from both the hair germ and the bulge, they also confirmed that the two are molecularly very similar, suggesting that the germ originates from the bulge. The researchers believe that toward the end of the resting phase, the hair germ is activated to reproduce before the bulge and they showed that the activating signal comes from a structure known as the dermal papilla.
“We discovered that the dynamics of the hair follicle regeneration is a two-step process,” said Valentina Greco, a visiting postdoctoral fellow who spearheaded the project. “The hair germ, which is in constant contact with the dermal papilla, gets activated first and the bulge is then called to contribute later during growth.”
It was previously recognised that two inhibitory signals, known as Wnts and BMP, were needed for hair follicle stem cells to activate. They have now identified an additional activation signal, a growth factor called FGF7 that is made by the dermal papilla and steadily increases throughout the resting phase.
“We think that FGF7 might contribute, along with the Wnts and BMP inhibitory signals, to coax the hair germ to divide and proliferate,” Fuchs said.
Greco explains that this makes sense since. Unlike the bulge stem cells, hair germ cells respond and proliferate quickly but soon exhaust their proliferative potential. “This organisation prevents depletion of the bulge stem cells, which are long lived,” Greco said. “It also allows a rapid initial proliferation of the hair follicles.”
Fuchs and her team believe that this dual organisation of the stem cell niche could apply to other organs. “It could be that the two-step process we’ve identified is needed to achieve optimal organ regeneration, not only in the skin but also in the blood and intestine,” says Greco. “These organs have slow and fast cycling cells, much like the hair germ and the bulge, and have the capacity to self-renew and regenerate.”