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Review

Are hair follicle stem cells promising candidates for wound healing?

, , , &
Pages 119-128 | Received 25 Aug 2018, Accepted 12 Dec 2018, Published online: 07 Jan 2019

References

  • Gonzales KAU, Fuchs E Skin and its regenerative powers: an alliance between stem cells and their niche. Dev Cell. 2017;43(4):387–401. PubMed PMID: 29161590; PubMed Central PMCID: PMCPMC5797699.
  • Natarajan S, Williamson D, Stiltz AJ, et al. Advances in wound care and healing technology. Am J Clin Dermatol. 2000;1(5):269–275. PubMed PMID: 11702318.
  • de Laat EH, van Den Boogaard MH, Spauwen PH, et al. Faster wound healing with topical negative pressure therapy in difficult-to-heal wounds: a prospective randomized controlled trial. Ann Plast Surg. 2011;67(6):626–631. PubMed PMID: 21629111.
  • Lutz NW, Confort-Gouny S, Casanova D, et al. Conditions of wound healing and cutaneous growth affect metabolic performance of skin following plastic surgery. Wound Repair Regen. 2007;15(4):491–496. PubMed PMID: 17650092.
  • Ansell DM, Kloepper JE, Thomason HA, et al. Exploring the “hair growth-wound healing connection”: anagen phase promotes wound re-epithelialization. J Invest Dermatol. 2011;131(2):518–528. PubMed PMID: 20927125.
  • Vagnozzi AN, Reiter JF, Wong SY Hair follicle and interfollicular epidermal stem cells make varying contributions to wound regeneration. Cell Cycle. 2015;14(21):3408–3417. PubMed PMID: 26398918; PubMed Central PMCID: PMCPMC4825603.
  • Brownell I, Guevara E, Bai CB, et al. Nerve-derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells. Cell Stem Cell. 2011;8(5):552–565. PubMed PMID: 21549329; PubMed Central PMCID: PMCPMC3089905.
  • Cheng C, Guo GF, Martinez JA, et al. Dynamic plasticity of axons within a cutaneous milieu. J Neurosci. 2010;30(44):14735–14744. PubMed PMID: 21048132.
  • Langton AK, Herrick SE, Headon DJ An extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. J Invest Dermatol. 2008;128(5):1311–1318. PubMed PMID: 18037901.
  • Nakrieko KA, Rudkouskaya A, Irvine TS, et al. Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury. Mol Biol Cell. 2011;22(14):2532–2540. PubMed PMID: 21593206; PubMed Central PMCID: PMCPMC3135478.
  • Strong AL, Neumeister MW, Levi B Stem cells and tissue engineering: regeneration of the skin and its contents. Clin Plast Surg. 2017;44(3):635–650. PubMed PMID: 28576253; PubMed Central PMCID: PMCPMC5513194.
  • Ma K, Tan Z, Zhang C, et al. Mesenchymal stem cells for sweat gland regeneration after burns: from possibility to reality. Burns. 2016;42(3):492–499. PubMed PMID: 26068210.
  • Li Q, Zhang C, Fu X Will stem cells bring hope to pathological skin scar treatment? Cytotherapy. 2016;18(8):943–956. PubMed PMID: 27293205.
  • Yang Z, He C, He J, et al. Curcumin-mediated bone marrow mesenchymal stem cell sheets create a favorable immune microenvironment for adult full-thickness cutaneous wound healing. Stem Cell Res Ther. 2018;9(1):21. PubMed PMID: 29386050; PubMed Central PMCID: PMCPMC5793416.
  • Sheng Z, Fu X, Cai S, et al. Regeneration of functional sweat gland-like structures by transplanted differentiated bone marrow mesenchymal stem cells. Wound Repair Regen. 2009;17(3):427–435. PubMed PMID: 19660052.
  • Li H, Fu X, Ouyang Y, et al. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell Tissue Res. 2006;326(3):725–736. PubMed PMID: 16906419.
  • Sheng L, Yang M, Liang Y, et al. Adipose tissue-derived stem cells (ADSCs) transplantation promotes regeneration of expanded skin using a tissue expansion model. Wound Repair Regen. 2013;21(5):746–754. PubMed PMID: 23937682.
  • Shingyochi Y, Orbay H, Mizuno H. Adipose-derived stem cells for wound repair and regeneration. Expert Opin Biol Ther. 2015;15(9):1285–1292. PubMed PMID: 26037027.
  • Wu YY, Jiao YP, Xiao LL, et al. Experimental study on effects of adipose-derived stem cell-seeded silk fibroin chitosan film on wound healing of a diabetic rat model. Ann Plast Surg. 2018;80(5):572–580. PubMed PMID: 29443833.
  • Akita S, Yoshimoto H, Ohtsuru A, et al. Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries. Radiat Prot Dosimetry. 2012;151(4):656–660. PubMed PMID: 22914335.
  • Kim BS, Kwon YW, Kong JS, et al. 3D cell printing of in vitro stabilized skin model and in vivo pre-vascularized skin patch using tissue-specific extracellular matrix bioink: a step towards advanced skin tissue engineering. Biomaterials. 2018;168:38–53. PubMed PMID: 29614431.
  • Zhao J, Hu L, Liu J, et al. The effects of cytokines in adipose stem cell-conditioned medium on the migration and proliferation of skin fibroblasts in vitro. Biomed Res Int. 2013;2013:578479. PubMed PMID: 24416724; PubMed Central PMCID: PMCPMC3876706.
  • Kilroy GE, Foster SJ, Wu X, et al. Cytokine profile of human adipose-derived stem cells: expression of angiogenic, hematopoietic, and pro-inflammatory factors. J Cell Physiol. 2007;212(3):702–709. PubMed PMID: 17477371.
  • Heo SC, Jeon ES, Lee IH, et al. Tumor necrosis factor-alpha-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms. J Invest Dermatol. 2011;131(7):1559–1567. PubMed PMID: 21451545.
  • Atalay S, Coruh A, Deniz K Stromal vascular fraction improves deep partial thickness burn wound healing. Burns. 2014;40(7):1375–1383. PubMed PMID: 24572074.
  • Ebrahimian TG, Pouzoulet F, Squiban C, et al. Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing. Arterioscler Thromb Vasc Biol. 2009;29(4):503–510. PubMed PMID: 19201690.
  • Chueh SC, Lin SJ, Chen CC, et al. Therapeutic strategy for hair regeneration: hair cycle activation, niche environment modulation, wound-induced follicle neogenesis, and stem cell engineering. Expert Opin Biol Ther. 2013;13(3):377–391. PubMed PMID: 23289545; PubMed Central PMCID: PMCPMC3706200.
  • Bickenbach JR Isolation, characterization, and culture of epithelial stem cells. Methods Mol Biol. 2005;289:97–102. PubMed PMID: 15502174.
  • Cotsarelis G, Sun TT, Lavker RM 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):1329–1337. PubMed PMID: 2364430.
  • Petersson M, Brylka H, Kraus A, et al. TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis. Embo J. 2011;30(15):3004–3018. PubMed PMID: 21694721; PubMed Central PMCID: PMCPMC3160179.
  • Rompolas P, Mesa KR, Greco V Spatial organization within a niche as a determinant of stem-cell fate. Nature. 2013;502(7472):513–518. PubMed PMID: 24097351; PubMed Central PMCID: PMCPMC3895444.
  • Snippert HJ, Haegebarth A, Kasper M, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science. 2010;327(5971):1385–1389. PubMed PMID: 20223988.
  • Nijhof JG, Braun KM, Giangreco A, et al. The cell-surface marker MTS24 identifies a novel population of follicular keratinocytes with characteristics of progenitor cells. Development. 2006;133(15):3027–3037. PubMed PMID: 16818453.
  • Page ME, Lombard P, Ng F, et al. The epidermis comprises autonomous compartments maintained by distinct stem cell populations. Cell Stem Cell. 2013;13(4):471–482. PubMed PMID: 23954751; PubMed Central PMCID: PMCPMC3793873.
  • Jaks V, Barker N, Kasper M, et al. Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet. 2008;40(11):1291–1299. PubMed PMID: 18849992.
  • Jaks V, Kasper M, Toftgard R The hair follicle-a stem cell zoo. Exp Cell Res. 2010;316(8):1422–1428. PubMed PMID: 20338163.
  • Plikus MV, Gay DL, Treffeisen E, et al. Epithelial stem cells and implications for wound repair. Semin Cell Dev Biol. 2012;23(9):946–953. PubMed PMID: 23085626; PubMed Central PMCID: PMCPMC3518754.
  • Lien WH, Polak L, Lin M, et al. In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators. Nat Cell Biol. 2014;16(2):179–190. PubMed PMID: 24463605; PubMed Central PMCID: PMCPMC3984009.
  • Choi YS, Zhang Y, Xu M, et al. Distinct functions for Wnt/beta-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell. 2013;13(6):720–733. PubMed PMID: 24315444; PubMed Central PMCID: PMCPMC3900235.
  • Oshima H, Rochat A, Kedzia C, et al. Morphogenesis and renewal of hair follicles from adult multipotent stem cells. Cell. 2001;104(2):233–245. PubMed PMID: 11207364.
  • Goodell MA, Nguyen H, Shroyer N Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments. Nat Rev Mol Cell Biol. 2015;16(5):299–309. PubMed PMID: 25907613; PubMed Central PMCID: PMCPMC5317203.
  • Gay D, Kwon O, Zhang Z, et al. Fgf9 from dermal gammadelta T cells induces hair follicle neogenesis after wounding. Nat Med. 2013;19(7):916–923. PubMed PMID: 23727932; PubMed Central PMCID: PMCPMC4054871.
  • Kadaja M, Keyes BE, Lin M, et al. SOX9: a stem cell transcriptional regulator of secreted niche signaling factors. Genes Dev. 2014;28(4):328–341. PubMed PMID: 24532713; PubMed Central PMCID: PMCPMC3937512.
  • Rhee H, Polak L, Fuchs E Lhx2 maintains stem cell character in hair follicles. Science. 2006;312(5782):1946–1949. PubMed PMID: 16809539; PubMed Central PMCID: PMCPMC2405918.
  • Folgueras AR, Guo X, Pasolli HA, et al. Architectural niche organization by LHX2 is linked to hair follicle stem cell function. Cell Stem Cell. 2013;13(3):314–327. PubMed PMID: 24012369; PubMed Central PMCID: PMCPMC3856689.
  • Mardaryev AN, Meier N, Poterlowicz K, et al. Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury. Development. 2011;138(22):4843–4852. PubMed PMID: 22028024; PubMed Central PMCID: PMCPMC4067271.
  • Nowak JA, Polak L, Pasolli HA, et al. Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell. 2008;3(1):33–43. PubMed PMID: 18593557; PubMed Central PMCID: PMCPMC2877596.
  • Nguyen H, Merrill BJ, Polak L, et al. Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia. Nat Genet. 2009;41(10):1068–1075. PubMed PMID: 19718027; PubMed Central PMCID: PMCPMC2792754.
  • Purba TS, Haslam IS, Shahmalak A, et al. Mapping the expression of epithelial hair follicle stem cell-related transcription factors LHX2 and SOX9 in the human hair follicle. Exp Dermatol. 2015;24(6):462–467. PubMed PMID: 25808706.
  • Keyes BE, Segal JP, Heller E, et al. Nfatc1 orchestrates aging in hair follicle stem cells. Proc Natl Acad Sci U S A. 2013;110(51):E4950–4959. PubMed PMID: 24282298; PubMed Central PMCID: PMCPMC3870727.
  • Ge Y, Gomez NC, Adam RC, et al. Stem cell lineage infidelity drives wound repair and cancer. Cell. 2017;169(4):636–650 e614. PubMed PMID: 28434617; PubMed Central PMCID: PMCPMC5510746.
  • Muller-Rover S, Handjiski B, van der Veen C, et al. A comprehensive guide for the accurate classification of murine hair follicles in distinct hair cycle stages. J Invest Dermatol. 2001;117(1):3–15. PubMed PMID: 11442744.
  • Hsu YC, Li L, Fuchs E Emerging interactions between skin stem cells and their niches. Nat Med. 2014;20(8):847–856. PubMed PMID: 25100530; PubMed Central PMCID: PMCPMC4358898.
  • Hsu YC, Pasolli HA, Fuchs E Dynamics between stem cells, niche, and progeny in the hair follicle. Cell. 2011;144(1):92–105. PubMed PMID: 21215372; PubMed Central PMCID: PMCPMC3050564.
  • Hsu YC, Li L, Fuchs E Transit-amplifying cells orchestrate stem cell activity and tissue regeneration. Cell. 2014;157(4):935–949. PubMed PMID: 24813615; PubMed Central PMCID: PMCPMC4041217.
  • Veltri A, Lang C, Lien WH Concise review: Wnt signaling pathways in skin development and epidermal stem cells. Stem Cells. 2018;36(1):22–35. . PubMed PMID: 29047191.
  • Xu Y, Fu X Development of hair follicle stem cells related signal transduction in proliferation and differentiation. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010;24(2):161–164. PubMed PMID: 20187446.
  • Jimenez F, Garde C, Poblet E, et al. A pilot clinical study of hair grafting in chronic leg ulcers. Wound Repair Regen. 2012;20(6):806–814. PubMed PMID: 23110506.
  • Liu JQ, Zhao KB, Feng ZH, et al. Hair follicle units promote re-epithelialization in chronic cutaneous wounds: a clinical case series study. Exp Ther Med. 2015;10(1):25–30. PubMed PMID: 26170907; PubMed Central PMCID: PMCPMC4486903.
  • Martinez Martinez ML, Escario Travesedo E, Jimenez Acosta F Hair-follicle transplant into chronic ulcers: a new graft concept. Actas Dermosifiliogr. 2017;108(6):524–531. PubMed PMID: 28438262.
  • Martinez ML, Escario E, Poblet E, et al. Hair follicle-containing punch grafts accelerate chronic ulcer healing: a randomized controlled trial. J Am Acad Dermatol. 2016;75(5):1007–1014. PubMed PMID: 27745629.
  • Tausche AK, Skaria M, Bohlen L, et al. An autologous epidermal equivalent tissue-engineered from follicular outer root sheath keratinocytes is as effective as split-thickness skin autograft in recalcitrant vascular leg ulcers. Wound Repair Regen. 2003;11(4):248–252. PubMed PMID: 12846911.
  • Ortega-Zilic N, Hunziker T, Lauchli S, et al. EpiDex(R) Swiss field trial 2004–2008. Dermatology. 2010;221(4):365–372. PubMed PMID: 21071921.
  • Chovatiya GL, Sarate RM, Sunkara RR, et al. Secretory phospholipase A2-IIA overexpressing mice exhibit cyclic alopecia mediated through aberrant hair shaft differentiation and impaired wound healing response. Sci Rep. 2017;7(1):11619. PubMed PMID: 28912581; PubMed Central PMCID: PMCPMC5599634.
  • Heidari F, Yari A, Rasoolijazi H, et al. Bulge hair follicle stem cells accelerate cutaneous wound healing in rats. Wounds. 2016;28(4):132–141. PubMed PMID: 27071141.
  • Stojadinovic O, Ito M, Tomic-Canic M Hair cycling and wound healing: to pluck or not to pluck? J Invest Dermatol. 2011;131(2):292–294. PubMed PMID: 21228812.
  • Claudinot S, Nicolas M, Oshima H, et al. Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc Natl Acad Sci U S A. 2005;102(41):14677–14682. PubMed PMID: 16203973; PubMed Central PMCID: PMCPMC1253596.
  • Ito M, Liu Y, Yang Z, et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med. 2005;11(12):1351–1354. PubMed PMID: 16288281.
  • Jimenez F, Poblet E, Izeta A Reflections on how wound healing-promoting effects of the hair follicle can be translated into clinical practice. Exp Dermatol. 2015;24(2):91–94. PubMed PMID: 25066054.
  • Chou WC, Takeo M, Rabbani P, et al. Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat Med. 2013;19(7):924–929. PubMed PMID: 23749232; PubMed Central PMCID: PMCPMC3859297.
  • Paus R, Nickoloff BJ, Ito T A ‘hairy’ privilege. Trends Immunol. 2005;26(1):32–40. PubMed PMID: 15629407.
  • Gurtner GC, Werner S, Barrandon Y, et al. Wound repair and regeneration. Nature. 2008;453(7193):314–321. PubMed PMID: 18480812.
  • Chermnykh E, Kalabusheva E, Vorotelyak E. Extracellular matrix as a regulator of epidermal stem cell fate. Int J Mol Sci. 2018;19(4). doi: 10.3390/ijms19041003. PubMed PMID: 29584689; PubMed Central PMCID: PMCPMC5979429.
  • Mecklenburg L, Tobin DJ, Muller-Rover S, et al. Active hair growth (anagen) is associated with angiogenesis. J Invest Dermatol. 2000;114(5):909–916. PubMed PMID: 10771470.
  • Murad A, Nath AK, Cha ST, et al. Leptin is an autocrine/paracrine regulator of wound healing. FASEB J. 2003;17(13):1895–1897. PubMed PMID: 12923067.
  • Sumikawa Y, Inui S, Nakajima T, et al. Hair cycle control by leptin as a new anagen inducer. Exp Dermatol. 2014;23(1):27–32. PubMed PMID: 24237265.
  • Watabe R, Yamaguchi T, Kabashima-Kubo R, et al. Leptin controls hair follicle cycling. Exp Dermatol. 2014;23(4):228–229. PubMed PMID: 24494978.
  • Xu ZC, Zhang Q, Li H Differentiation of human hair follicle stem cells into endothelial cells induced by vascular endothelial and basic fibroblast growth factors. Mol Med Rep. 2014;9(1):204–210. PubMed PMID: 24247660.
  • Quan R, Zheng X, Xu S, et al. Gelatin-chondroitin-6-sulfate-hyaluronic acid scaffold seeded with vascular endothelial growth factor 165 modified hair follicle stem cells as a three-dimensional skin substitute. Stem Cell Res Ther. 2014;5(5):118. PubMed PMID: 25331352; PubMed Central PMCID: PMCPMC4535258.
  • Quan R, Du W, Zheng X, et al. VEGF165 induces differentiation of hair follicle stem cells into endothelial cells and plays a role in in vivo angiogenesis. J Cell Mol Med. 2017;21(8):1593–1604. PubMed PMID: 28244687; PubMed Central PMCID: PMCPMC5542910.
  • Garcin CL, Ansell DM, Headon DJ, et al. Hair follicle bulge stem cells appear dispensable for the acute phase of wound re-epithelialization. Stem Cells. 2016;34(5):1377–1385. PubMed PMID: 26756547; PubMed Central PMCID: PMCPMC4985639.
  • Garcin CL, Ansell DM The battle of the bulge: re-evaluating hair follicle stem cells in wound repair. Exp Dermatol. 2017;26(2):101–104. PubMed PMID: 27574799.
  • White AC, Khuu JK, Dang CY, et al. Stem cell quiescence acts as a tumour suppressor in squamous tumours. Nat Cell Biol. 2014;16(1):99–107. PubMed PMID: 24335650; PubMed Central PMCID: PMCPMC3874399.
  • Adam RC, Yang H, Ge Y, et al. Temporal layering of signaling effectors drives chromatin remodeling during hair follicle stem cell lineage progression. Cell Stem Cell. 2018;22(3):398–413 e397. PubMed PMID: 29337183.
  • Huang C, Du Y, Nabzdyk CS, et al. Regeneration of hair and other skin appendages: a microenvironment-centric view. Wound Repair Regen. 2016;24(5):759–766. PubMed PMID: 27256925.
  • Kikuchi A, Yamamoto H, Kishida S Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal. 2007;19(4):659–671. PubMed PMID: 17188462.
  • Grumolato L, Liu G, Mong P, et al. Canonical and noncanonical Wnts use a common mechanism to activate completely unrelated coreceptors. Genes Dev. 2010;24(22):2517–2530. PubMed PMID: 21078818; PubMed Central PMCID: PMCPMC2975928.
  • Martinez S, Scerbo P, Giordano M, et al. The PTK7 and ROR2 protein receptors interact in the vertebrate WNT/Planar cell polarity (PCP) pathway. J Biol Chem. 2015;290(51):30562–30572. PubMed PMID: 26499793; PubMed Central PMCID: PMCPMC4683276.
  • Liu C, Li Y, Semenov M, et al. Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell. 2002;108(6):837–847. PubMed PMID: 11955436.
  • Logan CY, Nusse R The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810. PubMed PMID: 15473860.
  • Zhang C, Chen P, Fei Y, et al. Wnt/beta-catenin signaling is critical for dedifferentiation of aged epidermal cells in vivo and in vitro. Aging Cell. 2012;11(1):14–23. PubMed PMID: 21967252.
  • Lim X, Tan SH, Yu KL, et al. Axin2 marks quiescent hair follicle bulge stem cells that are maintained by autocrine Wnt/beta-catenin signaling. Proc Natl Acad Sci U S A. 2016;113(11):E1498–1505. PubMed PMID: 26903625; PubMed Central PMCID: PMCPMC4801317.
  • Peters F, Vorhagen S, Brodesser S, et al. Ceramide synthase 4 regulates stem cell homeostasis and hair follicle cycling. J Invest Dermatol. 2015;135(6):1501–1509. PubMed PMID: 25705848.
  • Deschene ER, Myung P, Rompolas P, et al. Beta-Catenin activation regulates tissue growth non-cell autonomously in the hair stem cell niche. Science. 2014;343(6177):1353–1356. PubMed PMID: 24653033; PubMed Central PMCID: PMCPMC4096864.
  • Kandyba E, Leung Y, Chen YB, et al. Competitive balance of intrabulge BMP/Wnt signaling reveals a robust gene network ruling stem cell homeostasis and cyclic activation. Proc Natl Acad Sci U S A. 2013;110(4):1351–1356. PubMed PMID: 23292934; PubMed Central PMCID: PMCPMC3557042.
  • Smith AA, Li J, Liu B, et al. Activating hair follicle stem cells via R-spondin2 to stimulate hair growth. J Invest Dermatol. 2016;136(8):1549–1558. PubMed PMID: 27109869.
  • Si Y, Bai J, Wu J, et al. LncRNA PlncRNA1 regulates proliferation and differentiation of hair follicle stem cells through TGFbeta1mediated Wnt/betacatenin signal pathway. Mol Med Rep. 2018;17(1):1191–1197. PubMed PMID: 29115537.
  • Cai B, Zheng Y, Ma S, et al. Long noncoding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway. Mol Med Rep. 2018;17(4):5477–5483. PubMed PMID: 29393477.
  • Bastakoty D, Young PP Wnt/beta-catenin pathway in tissue injury: roles in pathology and therapeutic opportunities for regeneration. FASEB J. 2016;30(10):3271–3284. PubMed PMID: 27335371; PubMed Central PMCID: PMCPMC5024694.
  • Whyte JL, Smith AA, Helms JA Wnt signaling and injury repair. Cold Spring Harb Perspect Biol. 2012;4(8):a008078. PubMed PMID: 22723493; PubMed Central PMCID: PMCPMC3405869.
  • Qiu W, Lei M, Li J, et al. Activated hair follicle stem cells and Wnt/beta-catenin signaling involve in pathnogenesis of sebaceous neoplasms. Int J Med Sci. 2014;11(10):1022–1028. PubMed PMID: 25076848; PubMed Central PMCID: PMCPMC4115241.
  • Cheon SS, Cheah AY, Turley S, et al. Beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds. Proc Natl Acad Sci U S A. 2002;99(10):6973–6978. PubMed PMID: 11983872; PubMed Central PMCID: PMCPMC124513.
  • Wei J, Melichian D, Komura K, et al. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma? Arthritis Rheum. 2011;63(6):1707–1717. PubMed PMID: 21370225; PubMed Central PMCID: PMCPMC3124699.
  • Keyes BE, Liu S, Asare A, et al. Impaired epidermal to dendritic T cell signaling slows wound repair in aged skin. Cell. 2016;167(5):1323–1338 e1314. PubMed PMID: 27863246; PubMed Central PMCID: PMCPMC5364946.
  • Ebert LM, Meuter S, Moser B Homing and function of human skin gammadelta T cells and NK cells: relevance for tumor surveillance. J Immunol. 2006;176(7):4331–4336. PubMed PMID: 16547270.
  • Gray EE, Suzuki K, Cyster JG Cutting edge: identification of a motile IL-17-producing gammadelta T cell population in the dermis. J Immunol. 2011;186(11):6091–6095. PubMed PMID: 21536803; PubMed Central PMCID: PMCPMC3098921.
  • Lee P, Gund R, Dutta A, et al. Stimulation of hair follicle stem cell proliferation through an IL-1 dependent activation of gammadeltaT-cells. Elife. 2017;6. doi: 10.7554/eLife.28875. PubMed PMID: 29199946; PubMed Central PMCID: PMCPMC5714500.
  • Fujisaki J, Wu J, Carlson AL, et al. In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche. Nature. 2011;474(7350):216–219. PubMed PMID: 21654805; PubMed Central PMCID: PMCPMC3725645.
  • Lu J, Meng H, Zhang A, et al. Phenotype and function of tissue-resident unconventional Foxp3-expressing CD4(+) regulatory T cells. Cell Immunol. 2015;297(1):53–59. PubMed PMID: 26142700.
  • Maryanovich M, Frenette PS T-regulating hair follicle stem cells. Immunity. 2017;46(6):979–981. PubMed PMID: 28636968.
  • Ali N, Zirak B, Rodriguez RS, et al. Regulatory T cells in skin facilitate epithelial stem cell differentiation. Cell. 2017;169(6):1119–1129 e1111. PubMed PMID: 28552347; PubMed Central PMCID: PMCPMC5504703.
  • Nosbaum A, Prevel N, Truong HA, et al. Cutting edge: regulatory T cells facilitate cutaneous wound healing. J Immunol. 2016;196(5):2010–2014. PubMed PMID: 26826250; PubMed Central PMCID: PMCPMC4761457.
  • Noguchi F, Nakajima T, Inui S, et al. Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice. PLoS One. 2014;9(8):e102271. PubMed PMID: 25122137; PubMed Central PMCID: PMCPMC4133190.
  • Nakajima T, Inui S, Fushimi T, et al. Roles of MED1 in quiescence of hair follicle stem cells and maintenance of normal hair cycling. J Invest Dermatol. 2013;133(2):354–360. PubMed PMID: 22931914.
  • Rittie L, Stoll SW, Kang S, et al. Hedgehog signaling maintains hair follicle stem cell phenotype in young and aged human skin. Aging Cell. 2009;8(6):738–751. PubMed PMID: 20050020.
  • Whyte JL, Smith AA, Liu B, et al. Augmenting endogenous Wnt signaling improves skin wound healing. PLoS One. 2013;8(10):e76883. PubMed PMID: 24204695; PubMed Central PMCID: PMCPMC3799989.
  • Rezza A, Wang Z, Sennett R, et al. Signaling networks among stem cell precursors, transit-amplifying progenitors, and their niche in developing hair follicles. Cell Rep. 2016;14(12):3001–3018. PubMed PMID: 27009580; PubMed Central PMCID: PMCPMC4826467.
  • Lu CP, Polak L, Keyes BE, et al. Spatiotemporal antagonism in mesenchymal-epithelial signaling in sweat versus hair fate decision. Science. 2016;354(6319). doi: 10.1126/science.aah6102. PubMed PMID: 28008008; PubMed Central PMCID: PMCPMC5333576.
  • Krieger K, Millar SE, Mikuda N, et al. NF-kappaB participates in mouse hair cycle control and plays distinct roles in the various pelage hair follicle types. J Invest Dermatol. 2018;138(2):256–264. PubMed PMID: 28942365.
  • Peled A, Sarig O, Samuelov L, et al. Mutations in TSPEAR, encoding a regulator of notch signaling, affect tooth and hair follicle morphogenesis. PLoS Genet. 2016;12(10):e1006369. PubMed PMID: 27736875; PubMed Central PMCID: PMCPMC5065119.
  • Stone RC, Pastar I, Ojeh N, et al. Epithelial-mesenchymal transition in tissue repair and fibrosis. Cell Tissue Res. 2016;365(3):495–506. PubMed PMID: 27461257; PubMed Central PMCID: PMCPMC5011038.
  • Imanishi H, Ansell DM, Cheret J, et al. Epithelial-to-mesenchymal stem cell transition in a human organ: lessons from lichen planopilaris. J Invest Dermatol. 2018;138(3):511–519. PubMed PMID: 29106928.
  • Chen Z, Wang Y, Shi C Therapeutic implications of newly identified stem cell populations from the skin dermis. Cell Transplant. 2015;24(8):1405–1422. PubMed PMID: 24972091.
  • Mani R Looking east. Int J Low Extrem Wounds. 2012;11(3):146. PubMed PMID: 23008341.
  • Purba TS, Haslam IS, Poblet E, et al. Human epithelial hair follicle stem cells and their progeny: current state of knowledge, the widening gap in translational research and future challenges. Bioessays. 2014;36(5):513–525. PubMed PMID: 24665045.
  • Quan R, Zheng X, Ni Y, et al. Culture and characterization of rat hair follicle stem cells. Cytotechnology. 2016;68(4):621–628. PubMed PMID: 25407732; PubMed Central PMCID: PMCPMC4960109.
  • Lyle S, Christofidou-Solomidou M, Liu Y, et al. The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Sci. 1998;111 (Pt 21):3179–3188. PubMed PMID: 9763512.
  • Michel M, Torok N, Godbout MJ, et al. Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage. J Cell Sci. 1996;109 (Pt 5):1017–1028. PubMed PMID: 8743949.
  • Kloepper JE, Tiede S, Brinckmann J, et al. Immunophenotyping of the human bulge region: the quest to define useful in situ markers for human epithelial hair follicle stem cells and their niche. Exp Dermatol. 2008;17(7):592–609. PubMed PMID: 18558994.
  • Purba TS, Brunken L, Peake M, et al. Characterisation of cell cycle arrest and terminal differentiation in a maximally proliferative human epithelial tissue: lessons from the human hair follicle matrix. Eur J Cell Biol. 2017;96(6):632–641. PubMed PMID: 28413121.
  • Burclaff J, Mills JC Cell biology: healthy skin rejects cancer. Nature. 2017;548(7667):289–290. PubMed PMID: 28783724.
  • Lo Celso C, Prowse DM, Watt FM Transient activation of beta-catenin signalling in adult mouse epidermis is sufficient to induce new hair follicles but continuous activation is required to maintain hair follicle tumours. Development. 2004;131(8):1787–1799. PubMed PMID: 15084463.
  • Kretzschmar K, Weber C, Driskell RR, et al. Compartmentalized epidermal activation of beta-catenin differentially affects lineage reprogramming and underlies tumor heterogeneity. Cell Rep. 2016;14(2):269–281. PubMed PMID: 26771241; PubMed Central PMCID: PMCPMC4713864.
  • MacDonald BT, Tamai K, He X Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9–26. PubMed PMID: 19619488; PubMed Central PMCID: PMCPMC2861485.
  • Morin PJ, Sparks AB, Korinek V, et al. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997;275(5307):1787–1790. PubMed PMID: 9065402.
  • Brown S, Pineda CM, Xin T, et al. Correction of aberrant growth preserves tissue homeostasis. Nature. 2017;548(7667):334–337. PubMed PMID: 28783732; PubMed Central PMCID: PMCPMC5675114.
  • Kajino Y, Yamaguchi A, Hashimoto N, et al. Beta-Catenin gene mutation in human hair follicle-related tumors. Pathol Int. 2001;51(7):543–548. PubMed PMID: 11472567.

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