Iranian Journal of Public Health 2017. 46(9):1167-1175.

Bulge Region as a Putative Hair Follicle Stem Cells Niche: A Brief Review



Background: Hair follicle stem cells exist in different sites. Most of the hair follicle stem cells are reside in niche called bulge. Bulge region is located between the opening of sebaceous gland and the attachment site of the arrector pili muscle.

Methods: Data were collected using databases and resources of PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from the earliest available published to identify English observational studies on hair follicle bulge region.

Results: Bulge stem cells are pluripotent with high proliferative capacity. Specific markers allow the bulge cells to be isolated from mouse or human hair follicle. Stem cells isolated from bulge region are label retaining and slow cycling hence these cells are defined as label-retaining cells. Bulge cell populations, due to their plasticity nature are able to differentiate into distinct linage and could contribute in tissue regeneration.

Conclusion: The current review discuss about bulge stem cells characteristics and biology including their cycle, location, plasticity, specific markers and regenerative nature. Also the differences between mouse and human hair follicles are investigated.




Bulge, Hair follicle, Stem cell, Regeneration, Pluripotent, Self-renewal

Full Text:



Waters JM, Richardson GD, Jahoda CA (2007). Hair follicle stem cells. Semin Cell Dev Biol, 18(2): 245–254.

Rompolas P, Greco V (2014). Stem cell dynamics in the hair follicle niche. Semin Cell Dev Biol, 25-26:34-42.

Zhang Y, Xiang M, Wang Y, et al (2006). Bulge cells of human hair follicles: segregation, cultivation and properties. Colloids Surf B Biointerfaces, 47(1): 50-6.

Inoue K, Aoi N, Sato T, et al (2009). Differential expression of stem-cell-associated markers in human hair follicle epithelial cells. Lab Invest, 89(8): 844–56.

Cotsarelis G (2006). Epithelial stem cells: a folliculocentric view. J Invest Dermatol, 126(7): 1459–68.

Ohyama M (2007). Hair follicle bulge: A fascinating reservoir of epithelial stem cells. J Dermatol Sci, 46(2): 81–9.

Harkey MR (1993). Anatomy and physiology of hair. Forensic Sci Int, 63(1-3): 9–18.

Ronald Shapiro, Paul Rose, Michael Morgan (2004). Hair anatomy and histology. In: Hair Transplantation. Eds, Unger W, Unger M, Unger WP, Shapiro R . 3rd ed. CRC Press. New York, pp. 25–33.

Botchkareva N, Randall VA (2009). The biology of hair growth. In: Cosmetic applications of laser and light-based system. Eds, Ahluwalia G. 1st Ed. William Andrew. New York, pp .3-35.

Chen CC, Plikus MV, Tang PC et al (2016). The Modulatable Stem Cell Niche: Tissue Interactions during Hair and Feather Follicle Regeneration J Mol Biol, 428(7):1423-40.

Won Oh J, Kloepper J, Langan EA et al (2016). A guide to studying human hair follicle cycling in vivo. J Invest Dermatol, 136(1): 34–44.

Eckert RL, Adhikary G, Balasubramanian S et al (2013). Biochemistry of epidermal stem cells. Biochim Biophys Acta, 1830(2): 2427–34.

Alonso L, Fuchs E (2006). The hair cycle. J Cell Sci, 119: 391–3.

Cotsarelis G (2006). Gene expression profiling gets to the root of human hair follicle stem cells. J Clin Invest, 116(1): 19–22.

Cotsarelis G, Sun TT, Lavker RM (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): 1329–37.

Hoffman RM (2006). The pluripotency of hair follicle stem cells. Cell Cycle, 5(3): 232–233.

Ma DR, Yang EN, Lee ST (2004). A review: the location, molecular characterisation and multipotency of hair follicle epidermal stem cells. Ann Acad Med Singapore, 33(6):784–788.

Morris RJ, Potten CS (1999). Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen. J Invest Dermatol, 112(4): 470–5.

Tumbar T, Guasch G, Greco V et al (2004). Defining the epithelial stem cell niche in skin. Science, 303(5656):359-63.

Lyle S, Christofidou-Solomidou M, Liu Y et al (1998). The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Sci, 111(Pt 21): 3179–88.

Trempus C, Morris RJ, Bortner CD et al (2003). Enrichment for living mouse keratinocytes from the hair follicle bulge with the cell surface marker CD34. J Invest Dermatol, 120(4):501-11.

Ohyama M, Terunuma A, Tock CL et al (2006). Characterization and isolation of stem cell-enriched human hair follicle bulge cells. J Clin Invest, 116(1): 249–260.

Morris RJ, Liu YP, Marles L et al (2004). Capturing and profiling adult hair follicle stem cells. Nat Biotechnol, 22(4):411-7.

Blanpain C, Lowry WE, Geoghegan A et al (2004). Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell, 118(5):635-48.

Boehnke K, Falkowska-Hansen B, Stark HJ et al (2012). Stem cells of the human epidermis and their niche: composition and function in epidermal regeneration and carcinogenesis. Carcinogenesis, 33(7): 1247–58.

Gutiérrez-Rivera A, Pavón-Rodríguez A, Jiménez-Acosta F et al (2010). Functional characterization of highly adherent CD34+ keratinocytes isolated from human skin. Exp Dermatol, 19(7): 685–8.

Amoh Y, Li L, Katsuoka K et al (2005). Multipotent nestin-posetive, keratin-negative hair follicle bulge cells can form neurons. Proc Natl Acad Sci U S A, 102(15): 5530–4.

Nobakht M, Najafzadeh N, Safari M et al (2010). Bulge Cells of Rat Hair Follicles: Isolation, Cultivation, Morphological and Biological Features. Yakhteh Med J, 12(1): 51–58.

Nobakht M, Asalgoo S, Rahbar Roshandel N et al (2011). Effects of Silibinin on Hair Follicle Stem Cells Differentiation to Neural-like Cells. Am J Mol Biol, 1: 212–22.

Garcin CL, Ansell DM, Headon, DJ et al (2016). Hair follicle bulge stem cells appear dispensable for the acute phase of wound re-epithelialization. Stem Cells, 34(5):1377-85.

Nishimura EK, Jordan SA, Oshima H et al (2002). Dominant role of the niche in melanocyte stem-cell fate determination. Nature, 416: 854–60.

Barclay AN, Wright GJ, Brooke G et al (2002). CD200 and membrane protein interactions in the control of myeloid cells. Trends Immunol, 23(6):285-90.

Ohyama M, Vogel JC, Amagai M (2007). Gene ontology analysis of human hair follicle bulge molecular signature. J Dermatol Sci, 45(2):147-50.

Carrasco E, Calvo MI, Blázquez-Castro A et al (2015). Photoactivation of ROS Production In Situ Transiently Activates Cell Proliferation in Mouse Skin and in the Hair Follicle Stem Cell Niche Promoting Hair Growth and Wound Healing. J Invest Dermatol, 135(11): 2611–22.

Huntzicker EG, Oro AE (2008). Controlling hair follicle signaling pathways through polyubiquitination. J Invest Dermatol, 128(5):1081-7.

Demehri S, Kopan R (2009). Notch signaling in bulge stem cells is notrequired for selection of hair follicle fate. Development, 136(6):891-6.

Taylor G, Lehrer MS, Jensen PJ et al (2000). Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell, 102(4):451-61.

Oshima H, Rochat A, Kedzia C et al (2001). Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell, 104(2):233-45.

Claudinot S, Nicolas M, Oshima H et al (2005). Long-term renewal of hair follicles from clonogenic multipotent stemcells. Proc Natl Acad Sci U S A, 102(49):17734-8.

Amoh Y, Li LN, Campillo R et al (2005). Implanted hair follicle stem cells form Schwann cells that support repair of severed peripheral nerves. Proc Natl Acad Sci U S A, 102(41):14677-82.

Drewa T, Joachimiak R, Kaznica A et al (2009). Primary cultures from rat vibrissae as a potential cell source for in vitro construction of urinary bladder wall grafts. Transplant Proc, 41(5):1932-5.

Yu H, Fang D, Kumar S et al (2006). Isolation of a novel population of multipotent adult stem cells from human hair follicles. Am J Pathol, 168(6):1879-88.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.