Stem cells mind the gap

Stem cells can sense stress and damage, and alert the immune system to help them repair the damage.

Stem cells residing within hair follicles (in red) can sense breaches in their niche and recruit immune cells (in green) to cope with tissue damage. Image credit: Lay et al. 2018 (CC BY 4.0)

Most, if not all, tissues of an adult animal contain stem cells. These stem cells regenerate and repair damaged tissues and organs for the entire lifetime of an animal, contributing to a healthy life. They divide to make daughter cells that become either new stem cells or specialized cells of that organ.

Adult stem cells exist in specific areas within tissues known as niches, where they interact with surrounding cells and molecules that inform their behavior. For example, cells and molecules within these niches can signal stem cells to remain in a ‘dormant’ state, but upon injury, they can mobilize stem cells to form new tissue and repair the wound. So far, it has been unclear how stem cells sense damage and stress and direct their efforts away from their normal duties towards repair.

Here, Lay et al. studied the stem cells in the mouse skin that are responsible to regenerate hair. Every hair follicle contains a niche (the ‘bulge’), where these stem cells live and share their environment with cells that anchor the hair. The niche tethers to the stem cells through specific adhesion molecules that also help the niche to form a tight seal to prevent bacteria from entering. Lay et al. removed one of the adhesion molecules called E-cadherin, which caused a breach in the niche’s barrier.

The stem cells sensed their damaged niche, prepared to multiply, and sent out stress signals to the immune system. The immune cells then arrived at the niche and sent signals back to the stem cells, prodding them to multiply and patch the barrier, while at the same time, keeping the inflammation in check. This remarkable ability of the stem cells to recruit immune cells and initiate a dialogue with them enabled the stem cells to divert their attention from regenerating hair and instead directing it towards the site of the tissue damage.

Other stem cells, such as those in the lung or gut, may have similar mechanisms to detect and respond to physical damage. It will be interesting to investigate the underlying mechanism of how immune cells are involved in balancing stem cell regenerative capacity and response to physical damage. A better knowledge of these processes could help to regenerate tissues or even entire organs.