Deciphering the molecular mechanisms of stem cell dynamics in hair follicle regeneration
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Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The crucial function of hair follicle stem cells is to maintain these hair growth cycles. Another vital aspect is the activity of melanocyte stem cells, which differentiate into melanin-producing melanocytes, contributing to skin and hair pigmentation. Sebaceous gland stem cells also have a pivotal role in maintaining the skin barrier by regenerating mature sebocytes. These stem cells are maintained in a specialized microenvironment or niche and are regulated by internal and external signals, determining their dynamic behaviors in homeostasis and hair follicle regeneration. The activity of these stem cells is tightly controlled by various factors secreted by the niche components around the hair follicles, as well as immune-mediated damage signals, aging, metabolic status, and stress. In this study, we review these diverse stem cell regulatory and related molecular mechanisms of hair regeneration and disease conditions. Molecular insights would provide new perspectives on the disease mechanisms as well as hair and skin disorder treatment.
Abstract
Hair follicles, which are connected to sebaceous glands in the skin, undergo cyclic periods of regeneration, degeneration, and rest throughout adult life in mammals. The crucial function of hair follicle stem cells is to maintain these hair growth cycles. Another vital aspect is the activity of melanocyte stem cells, which differentiate into melanin-producing melanocytes, contributing to skin and hair pigmentation. Sebaceous gland stem cells also have a pivotal role in maintaining the skin barrier by regenerating mature sebocytes. These stem cells are maintained in a specialized microenvironment or niche and are regulated by internal and external signals, determining their dynamic behaviors in homeostasis and hair follicle regeneration. The activity of these stem cells is tightly controlled by various factors secreted by the niche components around the hair follicles, as well as immune-mediated damage signals, aging, metabolic status, and stress. In this study, we review these diverse stem cell regulatory and related molecular mechanisms of hair regeneration and disease conditions. Molecular insights would provide new perspectives on the disease mechanisms as well as hair and skin disorder treatment.
참고문헌 (139)
- Schneider, M. R., "The hair follicle as a dynamic miniorgan", Curr. Biol, 19, pp.R132~R142 (2009)
- Hsu, Y. C., "Transit-amplifying cells orchestrate stem cell activity and tissue regeneration", Cell, 157, pp.935~949 (2014)
- Greco, V., "A two-step mechanism for stem cell activation during hair regeneration", Cell Stem Cell, 4, pp.155~169 (2009)
- Ito, M., "Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis", Nat. Med, 11, pp.1351~1354 (2005)
- Lee, S. A., "Stem cell-intrinsic mechanisms regulating adult hair follicle homeostasis", Exp. Dermatol, 30, pp.430~447 (2021)
- Plikus, M. V., "Cyclic dermal BMP signalling regulates stem cell activation during hair regeneration", Nature, 451, pp.340~344 (2008)
- Lay, K., "FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential", Proc. Natl Acad. Sci. USA, 113, pp.E1506~E1515 (2016)
- Wang, L., "Foxc1 reinforces quiescence in self-renewing hair follicle stem cells", Science, 351, pp.613~617 (2016)
- Horsley, V., "NFATc1 balances quiescence and proliferation of skin stem cells", Cell, 132, pp.299~310 (2008)
- Choi, Y. S., "Distinct functions for Wnt", beta-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis, 2013, pp.13, 720~733
- Sennett, R., "Mesenchymal-epithelial interactions during hair follicle morphogenesis and cycling", Semin. Cell Dev. Biol, 23, pp.917~927 (2012)
- Chen, C. L., "Functional com plexity of hair follicle stem cell niche and therapeutic targeting of niche dys function for hair regeneration", J. Biomed. Sci, 27, pp.43~ (2020)
- Jang, H., "Aging of hair follicle stem cells and their niches", BMB Rep, 56, pp.2~9 (2023)
- Paus, R., "‘hairy’ privilege", Trends Immunol, 6, pp.32~40 (2005)
- Bertolini, M., "Hair follicle immune privilege and its collapse in alopecia areata", Exp. Dermatol, 29, pp.703~725 (2020)
- Pratt, C. H., "Alopecia areata", Nat. Rev. Dis. Prim, 3, pp.17011~ (2017)
- Inui, S., "Androgen actions on the human hair follicle : perspectives", Exp. Dermatol, 22, pp.168~171 (2013)
- Ohnemus, U., "Hair cycle control by estrogens : catagen induction via estrogen receptor(ER)-alpha is checked by ER beta signaling", Endocrinology, 146, pp.1214~1225 (2005)
- Craven, A. J., "Prolactin signaling influences the timing mechanism of the hair follicle : analysis of hair growth cycles in prolactin receptor knockout mice", Endocrinology, 142, pp.2533~2539 (2001)
- Redler, S., "Genetics and other factors in the aetiology of female pattern hair loss", Exp. Dermatol, 26, pp.510~517 (2017)
- Lutz, G., "Hair loss and hyperprolactinemia in women", Dermatoendocrinol, 4, pp.65~71 (2012)
- Paus, R., "Hair follicle immune privilege revisited : the key to alopecia areata management", J. Investig. Dermatol Symp. Proc, 19, pp.S12~S17 (2018)
- Anzai, A., "Pathomechanisms of immune-mediated alopecia", Int Immunol, 31, pp.439~447 (2019)
- Randall, V. A., "Hormonal regulation of hair follicles exhibits a biological paradox", Semin. Cell Dev. Biol, 18, pp.274~285 (2007)
- Costin, G. E., "Human skin pigmentation : melanocytes modulate skin color in response to stress", FASEB J, 21, pp.976~994 (2007)
- Lin, J. Y., "Melanocyte biology and skin pigmentation", Nature, 445, pp.843~850 (2007)
- Dreno, B., "Microbiome in healthy skin, update for dermatologists", J. Eur. Acad. Dermatol Venereol, 30, pp.2038~2047 (2016)
- Geueke, A., "Stem and progenitor cells in sebaceous gland development, homeostasis and pathologies", Exp. Dermatol, 30, pp.588~597 (2021)
- Torkamani, N., "Destruction of the arrector pili muscle and fat infiltration in androgenic alopecia", Br. J. Dermatol, 170, pp.1291~1298 (2014)
- Muller-Rover, S., "A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages", J. Invest Dermatol, 117, pp.3~15 (2001)
- Augustyniak, A., "Dietary marine-derived ingredients for stimu lating hair cell cycle", Biomed. Pharmacother, 163, pp.114838~ (2023)
- Rezza, A., "Adult stem cell niches : cellular and molecular components", Curr. Top. Dev. Biol, 107, pp.333~372 (2014)
- Yi, R., "Concise review : mechanisms of quiescent hair follicle stem cell regulation", Stem Cells, 35, pp.2323~2330 (2017)
- Hsu, Y. C., "Dynamics between stem cells, niche, and progeny in the hair follicle", Cell, 144, pp.92~105 (2011)
- Hagner, A., "Transcriptional profiling of the adult hair follicle mesenchyme reveals r-spondin as a novel regulator of dermal progenitor function", iScience, 23, pp.101019~ (2020)
- Fuchs, E., "Tissue stem cells : architects of their niches", Cell Stem Cell, 27, pp.532~556 (2020)
- Yang, H., "Epithelial-mesenchymal micro niches govern stem cell lineage choices", Cell, 169, pp.483~496 (2017)
- Rompolas, P., "Spatial organization within a niche as a determinant of stem-cell fate", Nature, 502, pp.513~518 (2013)
- Heitman, N., "Dermal sheath contraction powers stem cell niche relocation during hair cycle regression", Science, 367, pp.161~166 (2020)
- Nishimura, E. K., "Dominant role of the niche in melanocyte stem-cell fate determination", Nature, 416, pp.854~860 (2002)
- Nishimura, E. K., "Melanocyte stem cells : a melanocyte reservoir in hair follicles for hair and skin pigmentation", Pigment Cell Melanoma Res, 24, pp.401~410 (2011)
- Qiu, W., "Regulation of melanocyte stem cells in the pigmentation of skin and its appendages: Biological patterning and therapeutic potentials", Exp. Dermatol, 28, pp.395~405 (2019)
- Chou, W. C., "Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling", Nat. Med, 19, pp.924~929 (2013)
- Niemann, C., "Development and homeostasis of the sebaceous gland", Semin. Cell Dev. Biol, 23, pp.928~936 (2012)
- Frances, D., "Stem cell dynamics in sebaceous gland morpho genesis in mouse skin", Dev. Biol, 363, pp.138~146 (2012)
- Fischer, H., "Holocrine secretion of sebum is a unique dnase2-dependent mode of programmed cell death", J. Invest. Dermatol, 137, pp.587~594 (2017)
- Schneider, M. R., "Sebocytes, multifaceted epithelial cells: lipid pro duction and holocrine secretion", Int. J. Biochem. Cell Biol, 42, pp.181~185 (2010)
- Zouboulis, C. C., "Beyond acne : current aspects of sebaceous gland biology and function", Rev. Endocr. Metab. Disord, 17, pp.319~334 (2016)
- Moore, K. A., "Stem cells and their niches", Science, 311, pp.1880~1885 (2006)
- Li, K. N., "Hair follicle stem cells as a skin-organizing signaling center during adult homeostasis", EMBO J, 40, pp.e107135~ (2021)
- Hsu, Y. C., "Emerging interactions between skin stem cells and their niches", Nat. Med, 20, pp.847~856 (2014)
- Brunet, A., "Ageing and rejuvenation of tissue stem cells and their niches", Nat. Rev. Mol. Cell Biol, 24, pp.45~62 (2023)
- Hsu, Y. C., "Building and maintaining the skin. Cold Spring Harb", Perspect. Biol, 14, pp.a040840~ (2022)
- Castellana, D., "Macrophages contribute to the cyclic activation of adult hair follicle stem cells", PLoS Biol, 12, pp.e1002002~ (2014)
- Gur-Cohen, S., "Stem cell-driven lymphatic remodeling coordinates tissue regeneration", Science, 366, pp.1218~1225 (2019)
- Genander, M., "BMP signaling and its pSMAD1", 5 target genes differentially regulate hair follicle stem cell lineages, 2014, pp.15, 619~633
- Kobielak, K., "Loss of a quiescent niche but not follicle stem cells in the absence of bone morphogenetic protein signaling", Proc. Natl Acad. Sci. USA, 104, pp.10063~10068 (2007)
- Kimura-Ueki, M., "Hair cycle resting phase is regulated by cyclic epithelial FGF18 signaling", J. Invest. Dermatol, 132, pp.1338~1345 (2012)
- Gay, D., "Fgf9 from dermal gammadelta T cells induces hair follicle neo genesis after wounding", Nat. Med, 19, pp.916~923 (2013)
- Harel, S., "Pharmacologic inhibition of JAK-STAT signaling promotes hair growth", Sci. Adv, 1, pp.e1500973~ (2015)
- Wang, E. C. E., "A subset of TREM2(+) dermal macrophages secretes oncostatin M to maintain hair follicle stem cell quiescence and inhibit hair growth", Cell Stem Cell, 24, pp.654~669 (2019)
- Myung, P. S., "Epithelial Wnt ligand secretion is required for adult hair follicle growth and regeneration", J. Invest. Dermatol, 133, pp.31~41 (2013)
- Leiros, G. J., "Androgens modify Wnt agonists", antagonists expression balance in dermal papilla cells preventing hair follicle stem cell differentiation in androgenetic alopecia, 2017, pp.439, 26~34
- Lien, W. H., "In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators", Nat. Cell Biol, 16, pp.179~190 (2014)
- Folgueras, A. R., "Architectural niche organization by LHX2 is linked to hair follicle stem cell function", Cell Stem Cell, 13, pp.314~327 (2013)
- Leishman, E., "Foxp1 maintains hair follicle stem cell quiescence through regulation of Fgf18", Development, 140, pp.3809~3818 (2013)
- Osorio, K. M., "Runx1 modulates developmental, but not injury-driven, hair follicle stem cell activation", Development, 135, pp.1059~1068 (2008)
- Chen, J. K., "IRX5 promotes DNA damage repair and activation of hair follicle stem cells", Stem Cell Rep, 18, pp.1227~1243 (2023)
- Haensel, D., "An Ovol2-Zeb1 transcriptional circuit regulates epithelial directional migration and proliferation", EMBO Rep, 20, pp.e46273~ (2019)
- Shirokova, V., "Foxi3 deficiency compromises hair follicle stem cell specifi cation and activation", Stem Cells, 34, pp.1896~1908 (2016)
- Adam, R. C., "Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice", Nature, 521, pp.366~370 (2015)
- Ren, X., "Lgr4 deletion delays the hair cycle and inhibits the activation of hair follicle stem cells", J. Invest. Dermatol, 140, pp.1706~1712 (2020)
- Jaks, V., "Lgr5 marks cycling, yet long-lived, hair follicle stem cells", Nat. Genet, 40, pp.1291~1299 (2008)
- Merrill, B. J., "Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin", Genes Dev, 15, pp.1688~1705 (2001)
- Wang, A. B., "Gata6 promotes hair follicle progenitor cell renewal by genome maintenance during proliferation", EMBO J, 36, pp.61~78 (2017)
- Adam, R. C., "NFI transcription factors provide chromatin access to maintain stem cell identity while preventing unintended lineage fate choices", Nat. Cell Biol, 22, pp.640~650 (2020)
- Pivetti, S., "Loss of PRC1 activity in different stem cell compartments acti vates a common transcriptional program with cell type-dependent outcomes", Sci. Adv, 5, pp.eaav1594~ (2019)
- Li, J., "Progressive alopecia reveals decreasing stem cell activation prob ability during aging of mice with epidermal deletion of DNA methyltransferase 1", J. Invest. Dermatol, 132, pp.2681~2690 (2012)
- Rabbani, P., "Coordinated activation of Wnt in epithelial and melanocyte stem cells initiates pigmented hair regeneration", Cell, 145, pp.941~955 (2011)
- Nishimura, E. K., "Key roles for transforming growth factor beta in mela nocyte stem cell maintenance", Cell Stem Cell, 6, pp.130~140 (2010)
- Chang, C. Y., "NFIB is a governor of epithelial-melanocyte stem cell beha viour in a shared niche", Nature, 495, pp.98~102 (2013)
- Takeo, M., "EdnrB governs regenerative response of melanocyte stem cells by crosstalk with Wnt signaling", Cell Rep, 15, pp.1291~1302 (2016)
- Botchkareva, N. V., "SCF", c-kit signaling is required for cyclic regeneration of the hair pigmentation unit, 2001, pp.15, 645~658
- Liao, C. P., "Identification of hair shaft progenitors that create a niche for hair pigmentation", Genes Dev, 31, pp.744~756 (2017)
- Veniaminova, N. A., "Niche-specific factors dynamically regulate sebaceous gland stem cells in the skin", Dev. Cell, 51, pp.326~340 (2019)
- Grose, R., "The role of fibroblast growth factor receptor 2b in skin home ostasis and cancer development", EMBO J, 26, pp.1268~1278 (2007)
- Clayton, R. W., "Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis", Br. J. Dermatol, 181, pp.677~690 (2019)
- Choa, R., "Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion", Science, 373, pp.eabd2893~ (2021)
- Kobayashi, T., "Homeostatic control of sebaceous glands by innate lymphoid cells regulates commensal bacteria equilibrium", Cell, 176, pp.982~997 (2019)
- Paus, R., "The hair follicle and immune privilege", J. Investig. Dermatol Symp. Proc, 8, pp.188~194 (2003)
- Rajabi, F., "Alopecia areata: a review of disease pathogenesis", Br. J. Dermatol, 179, pp.1033~1048 (2018)
- Paus, R., "Expression of classical and non-classical MHC class I antigens in murine hair follicles", Br. J. Dermatol, 131, pp.177~183 (1994)
- Ito, T., "Collapse and restoration of MHC class-I-dependent immune privi lege : exploiting the human hair follicle as a model", Am. J. Pathol, 164, pp.623~634 (2004)
- Hamed, F. N., "Alopecia areata patients show deficiency of FOXP3+CD39+ T regulatory cells and clonotypic restriction of Treg TCRbeta-chain, which high lights the immunopathological aspect of the disease", PLoS ONE, 14, pp.e0210308~ (2019)
- Raffin, C., "T(reg)cell-based therapies : challenges and perspectives", Nat. Rev. Immunol, 20, pp.158~172 (2020)
- Harries, M. J., "Lichen planopilaris is characterized by immune privilege collapse of the hair follicle’s epithelial stem cell niche", J. Pathol, 231, pp.236~247 (2013)
- Meyer, K. C., "Evidence that the bulge region is a site of relative immune privilege in human hair follicles", Br. J. Dermatol, 159, pp.1077~1085 (2008)
- Rosenblum, M. D., "CD200, a"no danger"signal for hair follicles", J. Dermatol. Sci, 41, pp.165~174 (2006)
- Harrist, T. J., "Distributionofmajor histocompatibility antigens in normal skin", Br. J. Dermatol, 109, pp.623~633 (1983)
- Yoshida, R., "Involvement of the bulge region with decreased expression of hair follicle stem cell markers in senile female cases of alopecia areata", J. Eur. Acad. Dermatol. Venereol, 25, pp.1346~1350 (2011)
- Ito, T., "Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack", J. Invest. Dermatol, 128, pp.1196~1206 (2008)
- Kono, M., "In situ expression of corticotropin-releasing hormone(CRH)and proopiomelanocortin(POMC)genes in human skin", FASEB J, 15, pp.2297~2299 (2001)
- Ito, N., "Corticotropin-releasing hormone stimulates the in situ generation of mast cells from precursors in the human hair follicle mesenchyme", J. Invest. Dermatol, 130, pp.995~1004 (2010)
- Agudo, J., "Quiescent tissue stem cells evade immune surveillance", Immunity, 48, pp.271~285 (2018)
- Harries, M. J., "Lichen planopilaris and frontal fibrosing alopecia as model epithelial stem cell diseases", Trends Mol. Med, 24, pp.435~448 (2018)
- Ho, B. S., "Progressive expression of PPARGC1alpha is associated with hair miniaturization in androgenetic alopecia", Sci. Rep, 9, pp.8771~ (2019)
- Matsumura, H., "Hair follicle aging is driven by transepidermal elimination of stem cells via COL17A1 proteolysis", Science, 351, pp.aad4395~ (2016)
- Zhang, C., "Escape of hair follicle stem cells causes stem cell exhaustion during aging", Nat. Aging, 1, pp.889~903 (2021)
- Rathnayake, D., "Male androgenetic alopecia", Expert Opin. Phar macother, 11, pp.1295~1304 (2010)
- Chen, C. C., "Regenerative hair waves in aging mice and extra-follicular modulators follistatin, dkk1, and sfrp4", J. Invest. Dermatol, 134, pp.2086~2096 (2014)
- Keyes, B. E., "Nfatc1 orchestrates aging in hair follicle stem cells", Proc. Natl Acad. Sci. USA, 110, pp.E4950~E4959 (2013)
- Choi, S., "Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence", Nature, 592, pp.428~432 (2021)
- Ge, Y., "The aging skin microenvironment dictates stem cell behavior", Proc. Natl Acad. Sci. USA, 117, pp.5339~5350 (2020)
- Koester, J., "Niche stiffening compromises hair follicle stem cell potential during ageing by reducing bivalent promoter accessibility", Nat. Cell Biol, 23, pp.771~781 (2021)
- Salzer, M. C., "Identity noise and adipogenic traits characterize dermal f ibroblast aging", Cell, 175, pp.1575~1590 (2018)
- Morinaga, H., "Obesity accelerates hair thinning by stem cell-centric con verging mechanisms", Nature, 595, pp.266~271 (2021)
- Flores, A., "Lactate dehydrogenase activity drives hair follicle stem cell activation", Nat. Cell Biol, 19, pp.1017~1026 (2017)
- Reichenbach, B., "Glutamate transporter Slc1a3 mediates inter-niche stem cell activation during skin growth", EMBO J, 37, pp.e98280~ (2018)
- Peters, F., "Ceramide synthase 4 regulates stem cell homeostasis and hair follicle cycling", J. Invest. Dermatol, 135, pp.1501~1509 (2015)
- Kim, C. S., "Glutamine metabolism controls stem cell fate reversibility and long-term maintenance in the hair follicle", Cell Metab, 32, pp.629~642 (2020)
- Nishimura, E. K., "Mechanisms of hair graying : incomplete melanocyte stem cell maintenance in the niche", Science, 307, pp.720~724 (2005)
- Inomata, K., "Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation", Cell, 137, pp.1088~1099 (2009)
- Dai, D. M., "Modeling human gray hair by irradiation as a valuable tool to study aspects of tissue aging", Geroscience, 45, pp.1215~1230 (2023)
- Zhang, B., "Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells", Nature, 577, pp.676~681 (2020)
- Zarei, M., "Low level laser therapy and hair regrowth : an evidence-based review", Lasers Med. Sci, 31, pp.363~371 (2016)
- Fertig, R. M., "Microneedling for the treatment of hair loss?", J. Eur. Acad. Dermatol. Venereol, 32, pp.564~569 (2018)
- Avci, P., "Low-level laser(light)therapy(LLLT)for treatment of hair loss", Lasers Surg. Med, 46, pp.144~151 (2014)
- Varothai, S., "Androgenetic alopecia : an evidence-based treat ment update", Am. J. Clin. Dermatol, 15, pp.217~230 (2014)
- Ellis, J. A., "Male pattern baldness : current treatments, future prospects", Drug Discov. Today, 13, pp.791~797 (2008)
- Xing, L., "Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition", Nat. Med, 20, pp.1043~1049 (2014)
- Damsky, W., "JAK inhibitors in dermatology : the promise of a new drug class", J. Am. Acad. Dermatol, 76, pp.736~744 (2017)
- King, B., "Two phase 3 trials of baricitinib for alopecia areata", N. Engl. J. Med, 386, pp.1687~1699 (2022)
- Goldstein, J., "Calcineurin", Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation, 2014, pp.28, 983~994
- Lee, J., "Runx1 and p21 synergistically limit the extent of hair follicle stem cell quiescence in vivo", Proc. Natl Acad. Sci. USA, 110, pp.4634~4639 (2013)
- Kadaja, M., "SOX9 : a stem cell transcriptional regulator of secreted niche signaling factors", Genes Dev, 28, pp.328~341 (2014)
- Hoeck, J. D., "Stem cell plasticity enables hair regeneration following Lgr5(+)cell loss", Nat. Cell Biol, 19, pp.666~676 (2017)
- Adam, R. C., "Temporal layering of signaling effectors drives chromatin remodeling during hair follicle stem cell lineage progression", Cell Stem Cell, 22, pp.398~413 (2018)
- Suen, W. J., "Hes1 regulates anagen initiation and hair follicle regeneration through modulation of hedgehog signaling", Stem Cells, 38, pp.301~314 (2020)
- Li, G., "SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice", EMBO J, 39, pp.e104365~ (2020)
