时空单细胞分析阐明了人类角膜老化的细胞和分子动力学。

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY
Dan Jiang, Ke Li, Yining Sun, Zicheng Zhang, Shuang Xie, Xintong Yu, Ruoqi Wang, Ying Feng, Qinxiang Zheng, Yajing Wen, Peter S Reinach, Yuanyuan Du, Meng Zhou, Wei Chen
{"title":"时空单细胞分析阐明了人类角膜老化的细胞和分子动力学。","authors":"Dan Jiang, Ke Li, Yining Sun, Zicheng Zhang, Shuang Xie, Xintong Yu, Ruoqi Wang, Ying Feng, Qinxiang Zheng, Yajing Wen, Peter S Reinach, Yuanyuan Du, Meng Zhou, Wei Chen","doi":"10.1186/s13073-025-01475-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The human cornea is a transparent and uniquely ordered optical-biological system. Precise coordination of its cellular mechanisms is essential to maintain its transparency and functionality. However, the spatial, cellular and molecular architecture of the human cornea and its intercellular interactions during aging have not been elucidated.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) and single-cell SpaTial Enhanced REsolution Omics-sequencing (scStereo-seq) analysis in corneal tissue from eight eyes of donors aged 33-88 years to elucidate the spatiotemporal cellular and molecular dynamics of human cornea aging. Immunofluorescence staining and Western blotting were performed to validate the findings.</p><p><strong>Results: </strong>Spatiotemporal single-cell analysis revealed the complex cellular landscape, spatial organization and intercellular communication within the human cornea. The subpopulations of major cell types of the cornea were elucidated with precise spatial positions. In particular, we identified novel subpopulations, mapped the spatial positioning of limbal stem cells within the limbal niche, and delineated the interactions between major cell types. We observed that three basal cell subsets migrate centripetally from the peripheral to the central cornea with age, suggesting the \"spatiotemporal centripetal pattern\" as a novel paradigm for the age-related migration of corneal epithelial cells. Furthermore, we elucidated the age-related, region-specific molecular and functional characteristics of the corneal endothelium, demonstrating differential metabolic capacities and functional properties between the peripheral and central regions.</p><p><strong>Conclusions: </strong>As the first comprehensive spatiotemporal atlas, our work provides a valuable resource for understanding tissue homeostasis in the human cornea and advances research on corneal pathology, transplantation, senescence and regenerative medicine in the context of corneal aging.</p>","PeriodicalId":12645,"journal":{"name":"Genome Medicine","volume":"17 1","pages":"56"},"PeriodicalIF":10.4000,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087038/pdf/","citationCount":"0","resultStr":"{\"title\":\"Spatiotemporal single-cell analysis elucidates the cellular and molecular dynamics of human cornea aging.\",\"authors\":\"Dan Jiang, Ke Li, Yining Sun, Zicheng Zhang, Shuang Xie, Xintong Yu, Ruoqi Wang, Ying Feng, Qinxiang Zheng, Yajing Wen, Peter S Reinach, Yuanyuan Du, Meng Zhou, Wei Chen\",\"doi\":\"10.1186/s13073-025-01475-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The human cornea is a transparent and uniquely ordered optical-biological system. Precise coordination of its cellular mechanisms is essential to maintain its transparency and functionality. However, the spatial, cellular and molecular architecture of the human cornea and its intercellular interactions during aging have not been elucidated.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing (scRNA-seq) and single-cell SpaTial Enhanced REsolution Omics-sequencing (scStereo-seq) analysis in corneal tissue from eight eyes of donors aged 33-88 years to elucidate the spatiotemporal cellular and molecular dynamics of human cornea aging. Immunofluorescence staining and Western blotting were performed to validate the findings.</p><p><strong>Results: </strong>Spatiotemporal single-cell analysis revealed the complex cellular landscape, spatial organization and intercellular communication within the human cornea. The subpopulations of major cell types of the cornea were elucidated with precise spatial positions. In particular, we identified novel subpopulations, mapped the spatial positioning of limbal stem cells within the limbal niche, and delineated the interactions between major cell types. We observed that three basal cell subsets migrate centripetally from the peripheral to the central cornea with age, suggesting the \\\"spatiotemporal centripetal pattern\\\" as a novel paradigm for the age-related migration of corneal epithelial cells. Furthermore, we elucidated the age-related, region-specific molecular and functional characteristics of the corneal endothelium, demonstrating differential metabolic capacities and functional properties between the peripheral and central regions.</p><p><strong>Conclusions: </strong>As the first comprehensive spatiotemporal atlas, our work provides a valuable resource for understanding tissue homeostasis in the human cornea and advances research on corneal pathology, transplantation, senescence and regenerative medicine in the context of corneal aging.</p>\",\"PeriodicalId\":12645,\"journal\":{\"name\":\"Genome Medicine\",\"volume\":\"17 1\",\"pages\":\"56\"},\"PeriodicalIF\":10.4000,\"publicationDate\":\"2025-05-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087038/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genome Medicine\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13073-025-01475-z\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genome Medicine","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13073-025-01475-z","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

摘要

背景:人的角膜是一个透明的、独特有序的光学生物系统。其细胞机制的精确协调对于保持其透明度和功能至关重要。然而,人类角膜的空间、细胞和分子结构及其在衰老过程中的细胞间相互作用尚未被阐明。方法:采用单细胞RNA测序(scRNA-seq)和单细胞空间增强分辨率组学测序(scStereo-seq)对8例33-88岁供体角膜组织进行分析,以阐明人类角膜衰老的时空细胞和分子动力学。采用免疫荧光染色和免疫印迹法对结果进行验证。结果:时空单细胞分析揭示了人角膜内部复杂的细胞格局、空间组织和细胞间通讯。通过精确的空间定位,阐明了角膜主要细胞类型的亚群。特别是,我们确定了新的亚群,绘制了角膜缘干细胞在角膜缘生态位中的空间定位,并描绘了主要细胞类型之间的相互作用。我们观察到,随着年龄的增长,三个基底细胞亚群从角膜外围向中心向心迁移,这表明“时空向心模式”是角膜上皮细胞年龄相关迁移的一种新模式。此外,我们阐明了年龄相关的、区域特异性的角膜内皮分子和功能特征,证明了周围和中心区域之间代谢能力和功能特性的差异。结论:作为第一个全面的时空图谱,我们的工作为了解人类角膜组织稳态提供了宝贵的资源,并在角膜衰老的背景下推进了角膜病理学、移植、衰老和再生医学的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spatiotemporal single-cell analysis elucidates the cellular and molecular dynamics of human cornea aging.

Background: The human cornea is a transparent and uniquely ordered optical-biological system. Precise coordination of its cellular mechanisms is essential to maintain its transparency and functionality. However, the spatial, cellular and molecular architecture of the human cornea and its intercellular interactions during aging have not been elucidated.

Methods: We performed single-cell RNA sequencing (scRNA-seq) and single-cell SpaTial Enhanced REsolution Omics-sequencing (scStereo-seq) analysis in corneal tissue from eight eyes of donors aged 33-88 years to elucidate the spatiotemporal cellular and molecular dynamics of human cornea aging. Immunofluorescence staining and Western blotting were performed to validate the findings.

Results: Spatiotemporal single-cell analysis revealed the complex cellular landscape, spatial organization and intercellular communication within the human cornea. The subpopulations of major cell types of the cornea were elucidated with precise spatial positions. In particular, we identified novel subpopulations, mapped the spatial positioning of limbal stem cells within the limbal niche, and delineated the interactions between major cell types. We observed that three basal cell subsets migrate centripetally from the peripheral to the central cornea with age, suggesting the "spatiotemporal centripetal pattern" as a novel paradigm for the age-related migration of corneal epithelial cells. Furthermore, we elucidated the age-related, region-specific molecular and functional characteristics of the corneal endothelium, demonstrating differential metabolic capacities and functional properties between the peripheral and central regions.

Conclusions: As the first comprehensive spatiotemporal atlas, our work provides a valuable resource for understanding tissue homeostasis in the human cornea and advances research on corneal pathology, transplantation, senescence and regenerative medicine in the context of corneal aging.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信