Human conjunctiva organoids to study ocular surface homeostasis and disease.

Autor:	Bannier-Hélaouët M; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, Utrecht, the Netherlands. Electronic address: m.bannier@hubrecht.eu., Korving J; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht, the Netherlands., Ma Z; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), and Department of Pharmacy, National University of Singapore, Singapore, Singapore., Begthel H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, Utrecht, the Netherlands., Giladi A; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, Utrecht, the Netherlands., Lamers MM; Viroscience Department, Erasmus University Medical Center, Rotterdam, the Netherlands., van de Wetering WJ; Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, the Netherlands., Yawata N; Department of Ocular Pathology and Imaging Science, Kyushu University, Fukuoka, Japan; Singapore Eye Research Institute, Singapore, Singapore; Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore., Yawata M; Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; National University Health System, Singapore, Singapore; Immunology Program, Life Sciences Institute, National University of Singapore, Singapore, Singapore; NUSMED Immunology Translational Research Program, National University of Singapore, Singapore, Singapore; Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A(∗)STAR), Singapore, Singapore; International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan., LaPointe VLS; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht, the Netherlands., Dickman MM; Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht, the Netherlands; University Eye Clinic Maastricht, Maastricht University Medical Center, Maastricht, the Netherlands., Kalmann R; Department of Ophthalmology, University Medical Center, Utrecht, the Netherlands., Imhoff SM; Department of Ophthalmology, University Medical Center, Utrecht, the Netherlands., van Es JH; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, Utrecht, the Netherlands., López-Iglesias C; Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, the Netherlands., Peters PJ; Maastricht Multimodal Molecular Imaging Institute, Maastricht University, Maastricht, the Netherlands., Haagmans BL; Viroscience Department, Erasmus University Medical Center, Rotterdam, the Netherlands., Wu W; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), and Department of Pharmacy, National University of Singapore, Singapore, Singapore., Clevers H; Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), University Medical Center, Utrecht, the Netherlands; Oncode Institute, Hubrecht Institute, Utrecht, the Netherlands. Electronic address: h.clevers@hubrecht.eu.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2024 Feb 01; Vol. 31 (2), pp. 227-243.e12. Date of Electronic Publication: 2024 Jan 11.
DOI:	10.1016/j.stem.2023.12.008
Abstrakt:	The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13 exposure increases goblet and tuft cell differentiation and drastically modifies the conjunctiva secretome. Human NGFR+ basal cells are identified as bipotent conjunctiva stem cells. Conjunctival cultures can be infected by herpes simplex virus 1 (HSV1), human adenovirus 8 (hAdV8), and SARS-CoV-2. HSV1 infection was reversed by acyclovir addition, whereas hAdV8 infection, which lacks an approved drug therapy, was inhibited by cidofovir. We document transcriptional programs induced by HSV1 and hAdV8. Finally, conjunctival organoids can be transplanted. Together, human conjunctiva organoid cultures enable the study of conjunctival (patho)-physiology. Competing Interests: Declaration of interests H.C. is the head of Pharma Research and Early Development at Roche, Basel and holds several patents related to organoid technology. M.B.-H. and H.C. are inventors on a filed patent application related to this work. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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