Hair follicles, like bacteria, don’t just live individual lives. They form communities, close-knit or otherwise, depending on the fullness of their molecular communications. When molecules are secreted and detected in greater or lesser quantities, they can signal populations that it is time to indulge in luxuriant growth, or recede.
This form of molecular communications, called quorum sensing, has been extensively studied in bacteria. The phenomenon, however, also occurs in the skin, where it serves as a kind of injury-response mechanism. And, as a recent study has determined, injuries due to hair plucking can actually stimulate hair stem cells, leading to thicker hair growth.
The new result appeared April 9 in the journal Cell, in an article entitled, “Organ-Level Quorum Sensing Directs Regeneration in Hair Stem Cell Populations.” The article indicated that by plucking hair at different densities, it is possible to regenerate up to five times more neighboring, unplucked resting hairs. According to the article’s authors, this response to plucking—to injury—suggests that a collective decision-making process is being activated.
This process was characterized as a form of quorum sensing by researchers led by Cheng-Ming Chuong, M.D., Ph.D., a stem cell principal investigator at the University of Southern California. A couple of years ago, Dr. Chuong began collaborating with visiting scholar Chih-Chiang Chen, Ph.D., who is affiliated with National Yang-Ming University and Veterans General Hospital, Taiwan.
As a dermatologist, Chen knew that hair follicle injury affects its adjacent environment, and the Chuong lab had already established that this environment in turn can influence hair regeneration. Based on this combined knowledge, they reasoned that they might be able to use the environment to activate more follicles.
To test this concept, Dr. Chen devised an elegant strategy to pluck 200 hair follicles, one by one, in different configurations on the back of a mouse. When plucking the hairs in a low-density pattern from an area exceeding six millimeters in diameter, no hairs regenerated. However, higher-density plucking from circular areas with diameters between three and five millimeters triggered the regeneration of between 450 and 1,300 hairs, including ones outside of the plucked region.
Working with Arthur D. Lander, M.D., Ph.D., from the University of California, Irvine, the team showed that this regenerative process relies on the principle of “quorum sensing,” which defines how a system responds to stimuli that affect some, but not all members.
“The range of the quorum signal was estimated to be on the order of one millimeter, greater than expected for a diffusible molecular cue,” wrote the authors of the Cell article. “Molecular and genetic analysis uncovered a two-step mechanism, where release of CCL2 from injured hairs leads to recruitment of TNF-α-secreting macrophages, which accumulate and signal to both plucked and unplucked follicles.”
Apparently, the quorum-sensing mechanism couples the immune response with regeneration, allowing skin to respond predictively to distress. Skin disregards mild injury, but meets stronger injury with full-scale cooperative activation of stem cells. Accordingly, stem cell social behavior can be exploited to enhance the reliability of regeneration.
“This work leads to potential new targets for treating alopecia, a form of hair loss,” said Dr. Chuong. “It is a good example of how basic research can lead to a work with potential translational value.”
Reflecting on the hair regeneration mechanism his team had characterized, Dr. Chuong noted that parallel mechanisms may also exist in the physiological or pathogenic processes of other organs. These other processes, however, “are not as easily observed as hair regeneration.”