Human conjunctiva organoids to study ocular surface homeostasis and disease

IF 19.8 1区 医学 Q1 CELL & TISSUE ENGINEERING Cell stem cell Pub Date : 2024-01-11 DOI:10.1016/j.stem.2023.12.008
Marie Bannier-Hélaouët, Jeroen Korving, Ziliang Ma, Harry Begthel, Amir Giladi, Mart M. Lamers, Willine J. van de Wetering, Nobuyo Yawata, Makoto Yawata, Vanessa L.S. LaPointe, Mor M. Dickman, Rachel Kalmann, Saskia M. Imhoff, Johan H. van Es, Carmen López-Iglesias, Peter J. Peters, Bart L. Haagmans, Wei Wu, Hans Clevers
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Abstract

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.

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研究眼表稳态和疾病的人类结膜器官组织
覆盖眼球的结膜上皮包含两种主要细胞类型:分泌粘液的鹅口疮细胞和分泌水的角质细胞,后者的顶端表面有粘蛋白。在这里,我们描述了代表小鼠和人类结膜的长期扩张的有机体和气液界面。原代和培养人结膜的单细胞 RNA 表达图谱显示,角质形成细胞表达多种抗菌肽,并能识别结膜簇细胞。IL-4/-13的暴露增加了鹅口疮细胞和簇细胞的分化,并极大地改变了结膜的分泌组。人类 NGFR+ 基底细胞被鉴定为双能结膜干细胞。结膜培养物可受单纯疱疹病毒1(HSV1)、人类腺病毒8(hAdV8)和SARS-CoV-2感染。加入阿昔洛韦可逆转 HSV1 感染,而 hAdV8 感染则可被西多福韦抑制,因为 hAdV8 感染缺乏经批准的药物疗法。我们记录了HSV1和hAdV8诱导的转录程序。最后,结膜有机体可以移植。总之,人类结膜类器官培养物有助于研究结膜(病理)生理学。
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来源期刊
Cell stem cell
Cell stem cell 生物-细胞生物学
CiteScore
37.10
自引率
2.50%
发文量
151
审稿时长
42 days
期刊介绍: Cell Stem Cell is a comprehensive journal covering the entire spectrum of stem cell biology. It encompasses various topics, including embryonic stem cells, pluripotency, germline stem cells, tissue-specific stem cells, differentiation, epigenetics, genomics, cancer stem cells, stem cell niches, disease models, nuclear transfer technology, bioengineering, drug discovery, in vivo imaging, therapeutic applications, regenerative medicine, clinical insights, research policies, ethical considerations, and technical innovations. The journal welcomes studies from any model system providing insights into stem cell biology, with a focus on human stem cells. It publishes research reports of significant importance, along with review and analysis articles covering diverse aspects of stem cell research.
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