Mechanosensation in Hair Follicles: Insights from Northwestern Study

Northwestern Medicine researchers have unveiled critical mechanisms by which hair follicle stem cells (HF-SCs) sense their environment and regulate their growth, as detailed in a recent study published in the esteemed journal Science Advances on June 17, 2025. This groundbreaking research addresses how these cells, which play a pivotal role in hair growth and regeneration throughout an individual's life, perceive physical forces and translate them into biological signals.

The lead researcher, Dr. Rui Yi, the Paul E. Steiner Research Professor of Pathology and a professor of Dermatology at Northwestern University, emphasized the importance of understanding how HF-SCs maintain their resting state. "The question is how cells sense mechanical force and how they translate that force into signals to tell them what to do, which has not previously been clear," said Dr. Yi, who is the senior author of the study.

In the study, conducted primarily in mice, the researchers discovered that HF-SCs employ the PIEZO1 ion channel to detect mechanical forces, such as the tension between cells and pressure from surrounding tissues. PIEZO1 is classified as a mechanosensitive ion channel, activating in response to physical stimuli and facilitating the influx of calcium ions into the cells. This calcium influx is critical for maintaining the quiescent state of the stem cells, which is vital for their longevity and function.

The research team utilized advanced imaging techniques to observe the dynamics of calcium flow within the HF-SCs. They noted that HF-SCs are interconnected by E-cadherin, a protein functioning like molecular Velcro, which plays a significant role in force transmission. The study revealed that when E-cadherin is subjected to a pulling force of approximately 20 picoNewtons (a trillionth of a Newton), PIEZO1 becomes activated, leading to brief surges of calcium—termed "calcium flickers"—entering the cells. These flickers are essential for maintaining the stem cells in their dormant state.

"When we deleted the PIEZO1 gene in these stem cells, they received fewer calcium signals and were more likely to exit their dormant state," Dr. Yi explained. This finding indicates that PIEZO1 is critical for balancing the quiescence and activation of HF-SCs, thus influencing hair growth cycles.

Moreover, through single-cell genomic analysis, the researchers identified a network of genes governed by PIEZO1, with AP1 and NFATC1 being particularly significant. These genes encode transcription factors essential for regulating cell structure and adhesion, reinforcing the specialized mechanical environment necessary for maintaining HF-SCs' dormancy.

Dr. Yi noted, "Mechanical force sensing and the downstream regulation are really important to controlling hair follicle stem cell activities. When we get older, the frequency of hair growth decreases. We want to know whether we can leverage some of our findings by manipulating specific mechanical forces to change stem cell behavior to stimulate their division or activation."

While the study was conducted using a murine model, Dr. Yi expressed optimism about translating these findings to human applications. "The study was just done in mice as a proof of principle. Maybe one day we can start to treat human hair loss disorders," he stated.

This research not only advances the understanding of hair follicle biology but also opens new avenues for therapeutic strategies aimed at hair loss and regenerative medicine. As the scientific community continues to explore the complex interplay between mechanical forces and cell behavior, the implications for treating hair loss and enhancing regenerative therapies are significant.

For further details, refer to the original article: Jingjing Wang et al, "PIEZO1-mediated calcium signaling reinforces mechanical properties of hair follicle stem cells to promote quiescence," Science Advances, 2025. DOI: 10.1126/sciadv.adt2771.