An Introduction to Hair Follicle Stem Cells

Hair follicle stem cells: An introduction to their biology, function, and significance in hair growth and regeneration Hair follicle stem cells (HFSCs) are self-renewing multipotent stem cells that reside primarily in the bulge region of hair follicles (Cotsarelis et al., 1990). These specialized cells play a crucial role in the hair growth cycle, as well as in the repair and regeneration of damaged skin tissues (Fuchs, 2007). HFSCs are characterized by their ability to differentiate into various cell types, proliferate, and regenerate hair follicles and surrounding epidermal structures during normal homeostasis and in response to injury (Blanpain & Fuchs, 2009). The bulge region, where the HFSCs are located, acts as a niche that provides a unique microenvironment that maintains stem cell properties and ensures proper cellular functions (Oshima et al., 2001). These cells are largely quiescent during the resting phase (telogen) of the hair growth cycle but become active during the growing phase (anagen) to generate new hair follicles and associated structures (Greco et al., 2009). The importance of HFSCs in hair growth lies in their ability to maintain a constant supply of cells for the continuous regeneration of hair follicles throughout the lifespan of an organism (Alonso & Fuchs, 2006). Additionally, HFSCs have been shown to respond to various growth factors and signaling pathways that regulate hair follicle development and growth, such as Wnt/β-catenin, sonic hedgehog (SHH), and bone morphogenic proteins (BMPs) (Millar et al., 1999; Botchkarev et al., 1999; Sennett & Rendl, 2012). Beyond their role in hair growth, HFSCs have recently gained attention for their critical involvement in skin regeneration following injury or during the wound healing process (Ito et al., 2005). In response to skin damage or wounding, HFSCs exhibit robust proliferative and migratory capacities as they mobilize to the site of injury, differentiate into functional cells, and contribute to re-epithelialization (Chen et al., 2015). A deeper understanding of the biology and function of HFSCs, including their regulatory pathways and interactions with surrounding cells, holds significant promise for the development of novel therapeutic approaches to treat alopecia and various skin-related diseases, as well as regenerative medicine applications (Garza et al., 2011). References: Alonso, L., & Fuchs, E (2006). The hair cycle. J. Cell Science, 119:391-393. Blanpain, C., & Fuchs, E. (2009). Epidermal homeostasis: a balancing act of stem cells in the skin. Nature Reviews Molecular Cell Biology, 10, 207-217. Botchkarev, V. A., Botchkareva, N. V., Roth, W., Nakamura, M., Chen, L. H., Herzog, W., ... & Paus, R. (1999). Noggin is a mesenchymally derived stimulator of hair-follicle induction. Nature cell biology, 1(3), 158-164. Chen, C. C., Wang, L., Plikus, M. V., Jiang, T. X., Murray, P. J., Ramos, R., ... & Chuong, C. M. (2015). Organ-level quorum sensing directs regeneration in hair stem cell populations. Cell, 161(2), 277-290. Cotsarelis, G., Sun, T. T., & Lavker, R. M. (1990). Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell, 61(7), 1329-1337. Fuchs, E. (2007). Scratching the surface of the skin development. Nature, 445(7130), 834-842. Garza, L. A., Yang, C. C., Zhao, T., Blatt, H. B., Lee, M., He, H., ... & Cotsarelis, G. (2011). Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells. Journal of Clinical Investigation, 121(2), 613-622. Greco, V., Chen, T., Rendl, M., Schober, M., Pasolli, H. A., Stokes, N., ... & Fuchs, E. (2009). A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell, 4(2), 155-169. Ito, M., Liu, Y., Yang, Z., Nguyen, J., Liang, F., Morris, R. J., & Cotsarelis, G. (2005). Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nature medicine, 11(12), 1351-1354. Millar, S. E., Willert, K., SAILLARD, V., SAILLARD, C., DENTE, L., KARRA, S., & VOLTZ, R. (1999). WNT signaling in the control of hair growth and structure. Developmental biology, 207(1), 133-149. Oshima, H., Rochat, A., Kedzia, C., Kobayashi, K., & Barrandon, Y. (2001). Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell, 104(2), 233-245. Sennett, R., & Rendl, M. (2012). Mesenchymal–epithelial interactions during hair follicle morphogenesis and cycling. Semin Cell Dev Biol, 23:917-927.