Adult stem cells provide the body with a reservoir from which damaged or used up tissues can be replenished. In organs like the intestines and skin, which need constant rejuvenating, these stem cells are dividing frequently. In other body structures, such as the hair follicles, they don’t reproduce until they receive signals from their surroundings that it’s time to regenerate; this is known as a quiescent state.

It makes intuitive sense that stem cells, being such a valuable resource, would be used sparingly.  However, scientists have limited understanding of how their quiescence is regulated, being unsure of its precise biological function. Now, a study from researchers at The Rockefeller University provides insights into the biological signals that make hair follicle stem cells oscillate between states of quiescence and regenerative activity.  The opensource study is published in the journal PNAS.

Previous studies show that a key provider of regulatory signals that balance stem cell quiescence and activity is the stem cell environment. Termed the ‘niche,’ it provides a residence for stem cells, and interacts with stem cells to regulate their behaviour and properties. Niche signals can originate from the immediate neighbours of the stem cells, or from the macroenvironment of the organ.  Earlier studies for the lab showed that when mice age, the old fat in their skin produces higher levels of a secreted signal, called BMP.  This signal acts as a molecular brake on the hair follicle stem cells, causing them to spend much longer times in quiescence.  The current study identified a stem cell gene that is activated by BMP signaling and showed that when this gene, Foxc1, is missing the stem cells grow hairs at dramatically shorter intervals.

The current study utilised mice that lack FOXC1, by disabling the gene that produces this protein they observed that the animals’ hair follicle stem cells spent more time growing hairs and less time in quiescence. Results show that over the course of nine months, while hair follicles from normal mice grew four new hairs, those from the FOXC1 knockout mice had already made new hairs seven times.  Data findings show that the knockout stem cells enter an overactive state in which they can’t establish quiescence adequately.

Results show that in the absence of FOXC1, hair follicles always had only one hair despite having made new hairs seven times. The group explain that this is because these hair follicles could not retain their old bulges, though they generated a new bulge without a problem. They go on to add that as the stem cells started proliferating more, they became less able to stick together, and as a result their old bulges did not stay properly tethered to the hair follicle when the newly growing hair pushed past it. Findings show that since the bulge emits quiescence signals, its loss activated the remaining stem cells even faster.

The team surmise that as hair follicle stem cells influence the behaviour of melanocyte stem cells, which co-inhabit the bulge niche; when the numbers of hair follicle stem cells declined with age, so too did the numbers of melanocyte stem cells, resulting in premature greying of whatever hairs were left.  For the future, the researchers state that not much is known about naturally occurring hair loss with age, however, these balding knockout mice may provide a model to study it.

Source: The Rockefeller University