Human Primary Epidermal Organoids Enable Modeling of Dermatophyte Infections

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2021 Jan 8

PMID 33414472

Citations 12

Authors

Xuan Wang

Shuyong Wang

Baolin Guo

Yuxin Su

Zuolong Tan

Mingyang Chang

Jinmei Diao

Yi Zhao

Yunfang Wang

Affiliations

Soon will be listed here.

Abstract

Technology of generating human epidermal derivatives with physiological relevance to in vivo epidermis is continuously investigated for improving their effects on modeling of human natural dermatological status in basic and clinical studies. Here, we report a method of robust establishment and expansion of human primary epidermal organoids (hPEOs) under a chemically defined condition. hPEOs reconstruct morphological, molecular, and functional features of human epidermis and can expand for 6 weeks. Remarkably, hPEOs are permissive for dermatophyte infections caused by Trichophyton Rubrum (T. rubrum). The T. rubrum infections on hPEOs reflect many aspects of known clinical pathological reactions and reveal that the repression on IL-1 signaling may contribute to chronic and recurrent infections with the slight inflammation caused by T. rubrum in human skin. Thus, our present study provides a new insight into the pathogenesis of T. rubrum infections and indicates that hPEOs are a potential ex vivo model for both basic studies of skin diseases and clinical studies of testing potential antifungal drugs.

Citing Articles

Organoids in skin wound healing.

Wang Z, Zhao F, Lang H, Ren H, Zhang Q, Huang X Burns Trauma. 2025; 13:tkae077.

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Trends and challenges in organoid modeling and expansion with pluripotent stem cells and somatic tissue.

Ge J, Wang Y, Li Q, Liu F, Lei Q, Zheng Y PeerJ. 2024; 12:e18422.

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Essential Guidelines for Manufacturing and Application of Organoids.

Ahn S, Lee S, Kwon D, Oh S, Park C, Jeon S Int J Stem Cells. 2024; 17(2):102-112.

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Bioengineered MSC transdifferentiated keratinocyte-like cell-derived organoid potentiates skin regeneration through ERK1/2 and STAT3 signaling in diabetic wound.

Choudhury S, Dhoke N, Chawla S, Das A Cell Mol Life Sci. 2024; 81(1):172.

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Advances in organoid technology for veterinary disease modeling.

Chen B, Slocombe R, Georgy S Front Vet Sci. 2023; 10:1234628.

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References

Huch M, Dorrell C, Boj S, van Es J, Li V, van de Wetering M . In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013; 494(7436):247-50. PMC: 3634804. DOI: 10.1038/nature11826. View

Lancaster M, Renner M, Martin C, Wenzel D, Bicknell L, Hurles M . Cerebral organoids model human brain development and microcephaly. Nature. 2013; 501(7467):373-9. PMC: 3817409. DOI: 10.1038/nature12517. View

Candi E, Schmidt R, Melino G . The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005; 6(4):328-40. DOI: 10.1038/nrm1619. View

Faway E, Lambert de Rouvroit C, Poumay Y . In vitro models of dermatophyte infection to investigate epidermal barrier alterations. Exp Dermatol. 2018; 27(8):915-922. DOI: 10.1111/exd.13726. View

Green H, Kehinde O, Thomas J . Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci U S A. 1979; 76(11):5665-8. PMC: 411710. DOI: 10.1073/pnas.76.11.5665. View

Goleva E, Berdyshev E, Leung D . Epithelial barrier repair and prevention of allergy. J Clin Invest. 2019; 129(4):1463-1474. PMC: 6436854. DOI: 10.1172/JCI124608. View

Boonekamp K, Kretzschmar K, Wiener D, Asra P, Derakhshan S, Puschhof J . Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures. Proc Natl Acad Sci U S A. 2019; 116(29):14630-14638. PMC: 6642409. DOI: 10.1073/pnas.1715272116. View

Simpson C, Patel D, Green K . Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol. 2011; 12(9):565-80. PMC: 3280198. DOI: 10.1038/nrm3175. View

Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen M . Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2014; 160(1-2):299-312. PMC: 4313365. DOI: 10.1016/j.cell.2014.11.050. View

10.

Sato K, Yang X, Yudate T, Chung J, Wu J, Luby-Phelps K . Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. J Biol Chem. 2006; 281(50):38854-66. DOI: 10.1074/jbc.M606542200. View

11.

Kretzschmar K, Clevers H . Wnt/β-catenin signaling in adult mammalian epithelial stem cells. Dev Biol. 2017; 428(2):273-282. DOI: 10.1016/j.ydbio.2017.05.015. View

12.

Hsu Y, Li L, Fuchs E . Emerging interactions between skin stem cells and their niches. Nat Med. 2014; 20(8):847-56. PMC: 4358898. DOI: 10.1038/nm.3643. View

13.

Igarashi M, Finch P, Aaronson S . Characterization of recombinant human fibroblast growth factor (FGF)-10 reveals functional similarities with keratinocyte growth factor (FGF-7). J Biol Chem. 1998; 273(21):13230-5. DOI: 10.1074/jbc.273.21.13230. View

14.

Lee J, Bscke R, Tang P, Hartman B, Heller S, Koehler K . Hair Follicle Development in Mouse Pluripotent Stem Cell-Derived Skin Organoids. Cell Rep. 2018; 22(1):242-254. PMC: 5806130. DOI: 10.1016/j.celrep.2017.12.007. View

15.

Vermout S, Tabart J, Baldo A, Mathy A, Losson B, Mignon B . Pathogenesis of dermatophytosis. Mycopathologia. 2008; 166(5-6):267-75. DOI: 10.1007/s11046-008-9104-5. View

16.

Boyce S, Kagan R, Yakuboff K, Meyer N, Rieman M, Greenhalgh D . Cultured skin substitutes reduce donor skin harvesting for closure of excised, full-thickness burns. Ann Surg. 2002; 235(2):269-79. PMC: 1422424. DOI: 10.1097/00000658-200202000-00016. View

17.

Sato T, Vries R, Snippert H, van de Wetering M, Barker N, Stange D . Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459(7244):262-5. DOI: 10.1038/nature07935. View

18.

DeWard A, Cramer J, Lagasse E . Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep. 2014; 9(2):701-11. PMC: 4223874. DOI: 10.1016/j.celrep.2014.09.027. View

19.

Ferby I, Reschke M, Kudlacek O, Knyazev P, Pante G, Amann K . Mig6 is a negative regulator of EGF receptor-mediated skin morphogenesis and tumor formation. Nat Med. 2006; 12(5):568-73. DOI: 10.1038/nm1401. View

20.

Prunieras M, Regnier M, Woodley D . Methods for cultivation of keratinocytes with an air-liquid interface. J Invest Dermatol. 1983; 81(1 Suppl):28s-33s. DOI: 10.1111/1523-1747.ep12540324. View