Local and Systemic Mechanisms That Control the Hair Follicle Stem Cell Niche

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2023 Oct 31

PMID 37903969

Authors

Bing Zhang

Ting Chen

Affiliations

Soon will be listed here.

Abstract

Hair follicles are essential appendages of the mammalian skin, as hair performs vital functions of protection, thermoregulation and sensation. Hair follicles harbour exceptional regenerative abilities as they contain multiple somatic stem cell populations such as hair follicle stem cells (HFSCs) and melanocyte stem cells. Surrounding the stem cells and their progeny, diverse groups of cells and extracellular matrix proteins are organized to form a microenvironment (called 'niche') that serves to promote and maintain the optimal functioning of these stem cell populations. Recent studies have shed light on the intricate nature of the HFSC niche and its crucial role in regulating hair follicle regeneration. In this Review, we describe how the niche serves as a signalling hub, communicating, deciphering and integrating both local signals within the skin and systemic inputs from the body and environment to modulate HFSC activity. We delve into the recent advancements in identifying the cellular and molecular nature of the niche, providing a holistic perspective on its essential functions in hair follicle morphogenesis, regeneration and ageing.

Citing Articles

Comparative proteomic analysis of the telogen-to-anagen transition in cashmere goat secondary hair follicles.

Han X, Gao G, Sun N, Dai B, Ren L, Bai H Front Vet Sci. 2025; 12:1542682.

PMID: 40070920 PMC: 11894581. DOI: 10.3389/fvets.2025.1542682.

Cholesterol promotes hair growth through activating sympathetic nerves and enhancing the proliferation of hair follicle stem cells.

Guo M, Jiang J, Zhang A, Yu W, Huang X Mol Med. 2025; 31(1):86.

PMID: 40045204 PMC: 11883958. DOI: 10.1186/s10020-025-01139-z.

Mitochondrial PGAM5 modulates methionine metabolism and feather follicle development by targeting Wnt/β-catenin signaling pathway in broiler chickens.

Zhang S, Chen Y, Lv Y, Feng Y, Gao C J Anim Sci Biotechnol. 2025; 16(1):35.

PMID: 40038789 PMC: 11881288. DOI: 10.1186/s40104-025-01176-y.

Immune and Non-immune Interactions in the Pathogenesis of Androgenetic Alopecia.

Xiao Y, Zhang Y, Deng S, Yang X, Yao X Clin Rev Allergy Immunol. 2025; 68(1):22.

PMID: 40024940 DOI: 10.1007/s12016-025-09034-5.

The Retinoic-Acid-Related Orphan Receptor Alpha May Be Highly Involved in the Regulation of Seasonal Hair Molting.

Zhang Y, Zhao X, Li S, Bai S, Zhang W Int J Mol Sci. 2025; 26(4).

PMID: 40004044 PMC: 11855665. DOI: 10.3390/ijms26041579.

References

Morris R, Potten C . Highly persistent label-retaining cells in the hair follicles of mice and their fate following induction of anagen. J Invest Dermatol. 1999; 112(4):470-5. DOI: 10.1046/j.1523-1747.1999.00537.x. View

Muller-Rover S, Handjiski B, van der Veen C, Eichmuller S, Foitzik K, McKay I . A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol. 2001; 117(1):3-15. DOI: 10.1046/j.0022-202x.2001.01377.x. View

Greco V, Chen T, Rendl M, Schober M, Pasolli H, Stokes N . A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 2009; 4(2):155-69. PMC: 2668200. DOI: 10.1016/j.stem.2008.12.009. View

Paus R, Cotsarelis G . The biology of hair follicles. N Engl J Med. 1999; 341(7):491-7. DOI: 10.1056/NEJM199908123410706. View

Rendl M, Polak L, Fuchs E . BMP signaling in dermal papilla cells is required for their hair follicle-inductive properties. Genes Dev. 2008; 22(4):543-57. PMC: 2238674. DOI: 10.1101/gad.1614408. View

Hsu Y, Pasolli H, Fuchs E . Dynamics between stem cells, niche, and progeny in the hair follicle. Cell. 2011; 144(1):92-105. PMC: 3050564. DOI: 10.1016/j.cell.2010.11.049. View

CHASE H . Growth of the hair. Physiol Rev. 1954; 34(1):113-26. DOI: 10.1152/physrev.1954.34.1.113. View

Craven A, Nixon A, Ashby M, Ormandy C, Blazek K, Wilkins R . Prolactin delays hair regrowth in mice. J Endocrinol. 2006; 191(2):415-25. DOI: 10.1677/joe.1.06685. View

Goldberg L, Lenzy Y . Nutrition and hair. Clin Dermatol. 2010; 28(4):412-9. DOI: 10.1016/j.clindermatol.2010.03.038. View

10.

Goldstein J, Fletcher S, Roth E, Wu C, Chun A, Horsley V . Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation. Genes Dev. 2014; 28(9):983-94. PMC: 4018496. DOI: 10.1101/gad.236554.113. View

11.

Shwartz Y, Gonzalez-Celeiro M, Chen C, Pasolli H, Sheu S, Mai-Yi Fan S . Cell Types Promoting Goosebumps Form a Niche to Regulate Hair Follicle Stem Cells. Cell. 2020; 182(3):578-593.e19. PMC: 7540726. DOI: 10.1016/j.cell.2020.06.031. View

12.

Zhang B, Ma S, Rachmin I, He M, Baral P, Choi S . Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells. Nature. 2020; 577(7792):676-681. PMC: 7184936. DOI: 10.1038/s41586-020-1935-3. View

13.

Cotsarelis G, Sun T, Lavker R . Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990; 61(7):1329-37. DOI: 10.1016/0092-8674(90)90696-c. View

14.

Tumbar T, Guasch G, Greco V, Blanpain C, Lowry W, Rendl M . Defining the epithelial stem cell niche in skin. Science. 2003; 303(5656):359-63. PMC: 2405920. DOI: 10.1126/science.1092436. View

15.

Blanpain C, Lowry W, Geoghegan A, Polak L, Fuchs E . Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell. 2004; 118(5):635-48. DOI: 10.1016/j.cell.2004.08.012. View

16.

Claudinot S, Nicolas M, Oshima H, Rochat A, Barrandon Y . Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc Natl Acad Sci U S A. 2005; 102(41):14677-82. PMC: 1253596. DOI: 10.1073/pnas.0507250102. View

17.

Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris R . Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med. 2005; 11(12):1351-4. DOI: 10.1038/nm1328. View

18.

Matsumura H, Mohri Y, Thanh Binh N, Morinaga H, Fukuda M, Ito M . Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis. Science. 2016; 351(6273):aad4395. DOI: 10.1126/science.aad4395. View

19.

Driskell R, Lichtenberger B, Hoste E, Kretzschmar K, Simons B, Charalambous M . Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature. 2013; 504(7479):277-281. PMC: 3868929. DOI: 10.1038/nature12783. View

20.

Driskell R, Watt F . Understanding fibroblast heterogeneity in the skin. Trends Cell Biol. 2014; 25(2):92-9. DOI: 10.1016/j.tcb.2014.10.001. View