Summary: Stem cells residing in hair follicles are held in an inactive state for long periods of time. A new study shows that these quiescent periods are essential for maintaining the cells’ rejuvenating activity over time and clarifies the mechanisms that bring the cells in and out of quiescence.
Adult stem cells serve as reservoir for the body from which damaged or used up tissues can be replenished. Like the intestines and skin, which needs constant regeneration, these stem cells are dividing frequently. However, in other body structures such as hair follicles, they are held in a quiescent state- one in which they don’t reproduce until they receive signals from their surroundings telling them it’s time to regenerate.
Stem cells being such a valuable is being used sparingly. Yet the scientists have limited understanding of how their quiescence is regulated and are even unsure of its precise biological function. In a study published in PNAS, researchers report on new insights into the biological signals that make their hair follicle stem cells oscillate between the states of quiescence and regenerative activity.
In an earlier study, it is 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.
In the current study, researchers identified a stem cell gene that is activated by BMP signaling and showed that when this gene is missing, the stem cells grow hairs with dramatically shorter intervals. It was initially thought that the key to hair growth might be the fountain of youth but the mice’s hair coat surprisingly thinned and greyed precociously.
More growth and fewer bulges:
Usually the stem cells create a new bulge along with the new hair while ensuring that the old bulge and the old hair stay put in the hair follicle. Only the new bulge can make another new hair, but the old bulge is kept in place to maintain a thick and lush coat. In mice, the hair follicles can accumulate up to four of these bulges.
Researchers created mice that lack FOXC-1 by disabling or “knocking out” the gene that produces this protein, they observed that the animals’ hair follicle stem cells spent more time growing hairs and less time quiescence. Over the course of 9 months, hair follicles from normal mice grew 4 new hairs, those from the FOXC-1 knockout mice had already made new hairs 7 times. The knock out stem cells enter an overactive state in which they can’t establish quiescence adequately.
Going grey and going bald:
While the hair follicle stem cells of FOXC-1 deficient mice produce hairs at a relatively breakneck pace, this growth seems to wear them out. Older knockout mice had sparser, greyer coats and could not regenerate their fur as quickly as their normal age matched or younger peers.
A similar phenomenon has been described in mice hematopoietic stem cells, that give rise to blood cells- those stem cells that are more active in young animals appear to become exhausted as the animal grow older.
Hair follicle stem cells influence the behavior of melanocyte stem cells, which co-inhabit the bulge niche. When the number of hair follicle stem cells declined with age, so do the numbers of melanocyte stem cells, resulting in premature greying of whatever hairs were left.
However not much is known about naturally occurring hair loss with age, but these balding knockout mice may provide a model to study it.