USC researchers have identified a novel cyclic signaling in the dermis that coordinates stem cell activity and regulates regeneration in large populations of hairs in animal models. The signaling switch involves the bone morphogenetic protein (Bmp) pathway, according to the study published in the Jan. 17 issue of the journal Nature.

“Conceptually, the findings have important implications for stem cell research and in understanding how stem cell activity is regulated during regeneration,” said Cheng-Ming Chuong, principal investigator and professor of pathology at the Keck School of Medicine. “The research presents a new dimension for the regulation of hair re-growth and ultimately organ regeneration.”

The hair is an important model for organ regeneration in mammals because it is one of the few organs that regenerate regularly, Chuong notes. Recent work in the field has established hair cycling as one of the mainstream models for organ regeneration. However, most of these works focus on the cyclic regeneration of one single hair follicle, he said.

“Each of us has thousands of hair follicles. In our study, we were motivated to analyze the coordinative behavior of cyclic regeneration in a population of organs,” Chuong said.

The research team found that hairs, even in normal mice, regenerate in waves, rather than individually. The findings suggest that hair stem cells are regulated not only by the micro-environment within one hair follicle—as has previously been thought—but also by adjacent hair follicles, other skin compartments and systemic hormones, in a hierarchical order.

At the molecular level, the findings showed that periodic expression of Bmp in the skin macro-environment appears to be at the center of the mechanism for coordinated hair stem cell activation. When many hairs regenerate, they must communicate activation signals among themselves. At different time points the macro-environment can be either permissive or suppressive for stem cell activation.

“Our research shows that the formation of new tissues or organs from stem cells—such as the formation of new hairs—can be more robust if it occurs in a permissive macro-environment,” said Maksim Plikus, a post-doctoral fellow and the first author of the study. “I hope that our research will draw more attention to the hair follicle as the model for physiological regeneration in mammals, and as an abundant source of adult stem cells for the purposes of stem cell therapy.”

“The work also has critical implications for the many researchers using the mouse skin as a model for tumor growth or drug delivery,” Chuong notes. “Many of these studies assume the mouse skin is a homogeneous and stable environment for testing, but variations in results were obtained. Understanding this unexpected dynamic of the living mouse skin will help their experimental designs.”

The study was funded by National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institute on Aging, the California Institute for Regenerative Medicine and the Research Councils U.K.

Maksim V. Plikus, Julie Ann Mayer, Damon de La Cruz, Ruth E. Baker, Philip K. Maini, Robert Maxson and Cheng-Ming Chuong. “Cyclic dermal BMP signaling regulates stem cell activation during hair regeneration,” Nature (2008). Doi: 10.1038/nature06457