Human conjunctiva organoids to study ocular surface homeostasis and disease

被引：13

作者：

Bannier-Helaouet, Marie ^{[1
,2
]}

Korving, Jeroen ^{[1
]}

Ma, Zilian ^{[3
,4
]}

Begthel, Harry ^{[1
,2
]}

Giladi, Amir ^{[1
,2
]}

Lamers, Mart M. ^{[5
]}

van de Wetering, Willine J. ^{[5
]}

Yawata, Nobuyo ^{[7
,8
,9
]}

Yawata, Makoto ^{[10
,11
,12
,13
,14
,15
,17
]}

LaPointe, Vanessa L. S. ^{[16
]}

Dickman, Mor M. ^{[16
]}

Kalmann, Rachel ^{[18
]}

Imhoff, Saskia M. ^{[18
]}

van Es, Johan H. ^{[1
,2
]}

Lopez-Iglesias, Carmen ^{[6
]}

Peters, Peter J. ^{[6
]}

Haagmans, Bart L. ^{[5
]}

Wu, Wei ^{[3
,4
]}

Clevers, Hans ^{[1
,2
,19
]}

机构：

[1] Univ Med Ctr Utrecht, Hubrecht Inst, Royal Netherlands Acad Arts & Sci KNAW, Utrecht, Netherlands

[2] Hubrecht Inst, Oncode Inst, Utrecht, Netherlands

[3] Natl Univ Singapore, Singapore Immunol Network SIgN, Agcy Sci Technol & Res A STAR, Singapore, Singapore

[4] Natl Univ Singapore, Dept Pharm, Singapore, Singapore

[5] Erasmus Univ, Virosci Dept, Med Ctr, Rotterdam, Netherlands

[6] Maastricht Univ, Maastricht Multimodal Mol Imaging Inst, Maastricht, Netherlands

[7] Kyushu Univ, Dept Ocular Pathol & Imaging Sci, Fukuoka, Japan

[8] Singapore Eye Res Inst, Singapore, Singapore

[9] Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore

[10] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pediat, Singapore, Singapore

[11] Natl Univ Hlth Syst, Singapore, Singapore

[12] Natl Univ Singapore, Life Sci Inst, Immunol Program, Singapore, Singapore

[13] Natl Univ Singapore, NUSMED Immunol Translat Res Programme, Singapore, Singapore

[14] ASTAR, Singapore Inst Clin Sci SICS, Singapore, Singapore

[15] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto, Japan

[16] MERLN Inst Technol Inspired Regenerat Med, Dept Cell Biol Inspired Tissue Engn, Maastricht, Netherlands

[17] Maastricht Univ, Med Ctr, Univ Eye Clin Maastricht, Maastricht, Netherlands

[18] Univ Med Ctr, Dept Ophthalmol, Utrecht, Netherlands

[19] F Hoffmann La Roche Ltd, Pharma Res & Early Dev, Basel, Switzerland

来源：

CELL STEM CELL | 2024年 / 31卷 / 02期

关键词：

EPITHELIAL-CELL CULTURE; STEM-CELLS; ADENOVIRAL KERATOCONJUNCTIVITIS; GOBLET CELLS; IN-VITRO; DIFFERENTIATION; EXPRESSION; SKIN; IDENTIFICATION; CORNEA;

D O I：

10.1016/j.stem.2023.12.008

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：227 / 243.e12

页数：30

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