Investigating Stem Cells that Stimulate Hair Growth

Sean Fletcher | sean.fletcher@yale.edu November 16, 2011

The mammalian skin system is marked by a high degree of complexity. Skin, the largest mammalian organ, harbors a highly diversified set of cells that engage in constant interplay, making it a viable topic of study. In particular, hair growth, one of the most prominent properties of the skin, is not yet fully understood. Valerie Horsley, Associate Professor of Molecular, Cellular, and Developmental Biology, and her associates have recently taken a closer look at hair growth in an effort to elucidate its biological foundation. In studying hair growth mechanisms, Horsley’s team has implicated intradermal adipocyte lineage cells in the activation of skin stem cells that induce hair growth.

Mammalian skin tissue: a harbor for stem cells. Photo courtesy of A.D.A.M.

The journey began when Horsley’s team observed a parallel between the hair growth cycle and the development of adipose tissue in the dermal layer of the skin. They noticed that the adipose layer enlarged as hair follicles grew and shrunk as hair follicles died down. The team later identified this adipose layer enlargement as adipogenesis, the process by which adipocyte precursor cells proliferate and mature. Since adipocyte lineage cells are already known to interact with other cell types, such as those in the skeletal muscle and bone marrow, Horsley set out to uncover how these adipocytes interact with skin cells. She hypothesized that these adipocyte precursor cells were directly responsible for hair follicle growth by inducing the activation of follicular stem cells. By establishing a link between these two cell types, Horsley’s team was breaking new ground.

The team employed various experimental methods, including histology and functional analysis, to visualize the interactions between the adipocyte lineage cells and the follicular stem cells. Furthermore, several mouse models with genetic mutations at different stages of the adipogenesis pathway were used to determine more specifically how adipocyte lineage cells contribute to the regulation of follicular stem cells. For example, one mouse model with a defect in adipocyte precursor proliferation resulted in a significant decrease in hair growth levels. Transplanting wild-type adipocyte precursor cells into regions where such precursors were lacking in the mutant mice, however, prompted hair growth. Additional tests showed that adipocyte precursors drive platelet derived growth factor (PDGF) signaling, a process that induces the hair follicle’s initiation of the growth phase. The data collected from these experiments showed that adipocyte precursor cells are both necessary and sufficient to drive hair follicle growth.

The differentiation pathway of the adipocyte lineage cells. Photo courtesy of Dr. Valerie Horsley.

The research conducted by Horsley’s team has improved the understanding of how follicular stem cell activation is positively regulated. The possible applications of the team’s findings are wide and far-reaching. For one, locating similar systems of adipogenesis and follicular stem cell interactions in humans could be the first steps toward reversing the effects of male pattern baldness. According to Horsley, “if we can get these fat cells in the skin to talk to the dormant stem cells at the base of hair follicles, we might be able to get hair to grow again.”