The Spatial Transcriptomic Atlas of Human Limbus and Vital Niche Microenvironment Regulating the Fate of Limbal Epithelial Stem Cells.

IF 5 2区医学 Q1 OPHTHALMOLOGY

Investigative ophthalmology & visual science Pub Date : 2025-03-03 DOI:10.1167/iovs.66.3.52

Shiding Li, Hao Sun, Fei Fang, Siyi Zhang, Junzhao Chen, Chunyi Shao, Yao Fu, Liangbo Chen

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Abstract

Purpose: This study aimed to generate the spatial atlas of the human limbus using spatial transcriptomic technology and reveal the deep interaction among the niche microenvironment.

Methods: The spatial transcriptomic atlas of human limbus was performed using 10× Genomics Space Ranger software platform. Single-cell RNA sequencing data of human limbal epithelial stem cells (LESCs) were downloaded for integrating analysis.

Results: We profiled more than 400 spots within each sample and spatially located major cell types within the limbus area. LESCs were localized mainly in the basement membrane, and limbal niche cells were situated predominantly within the stromal area. Next, the limbus was divided into four regions based on histological structure, and the differential expressed genes among the four regions were analyzed. Notably, GPHB5 was highly expressed in the epithelium of the middle region and co-staining with deltaNp63 suggested it might be a novel potential biomarker of LESCs. Subsequently, limbal mesenchymal stem cells were found to exhibit the greatest amounts of ligands associated with LESCs. The widespread activity of COL6A2/CD44 signaling among limbal mesenchymal stem cells, melanocytes, immune cells, and LESCs indicate its essential role in mediating bidirectional communication via the collagen pathway.

Conclusions: This research mapped the spatial positioning of key cells within the limbal niche and detailed interactions between major cell types. These findings provide a foundation for further LESC research and enhance our understanding of corneal biology.

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人类角膜缘空间转录组图谱及调节角膜缘上皮干细胞命运的生态位微环境。

目的：本研究旨在利用空间转录组学技术生成人类肢端空间图谱，揭示肢端微环境之间的深层相互作用：方法：利用 10× Genomics Space Ranger 软件平台绘制人类肢端空间转录组图谱。方法：利用 10× Genomics Space Ranger 软件平台绘制了人类肢端空间转录组图谱，并下载了人类肢端上皮干细胞（LESCs）的单细胞 RNA 测序数据进行整合分析：结果：我们对每个样本中的400多个点进行了分析，并对睑缘区域内的主要细胞类型进行了空间定位。LESC主要定位于基底膜，而边缘龛细胞主要位于基质区。接着，根据组织学结构将角膜缘分为四个区域，并分析了四个区域的差异表达基因。值得注意的是，GPHB5在中间区域的上皮细胞中高表达，并与deltaNp63共染，这表明它可能是LESCs的一种新的潜在生物标志物。随后，研究人员发现，肢端间充质干细胞表现出最大量的与LESCs相关的配体。COL6A2/CD44信号在肢端间充质干细胞、黑色素细胞、免疫细胞和LESCs中的广泛活性表明，它在通过胶原通路介导双向交流方面发挥着重要作用：这项研究绘制了边缘龛内关键细胞的空间定位图，并详细描述了主要细胞类型之间的相互作用。这些发现为进一步开展 LESC 研究奠定了基础，并加深了我们对角膜生物学的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Investigative ophthalmology & visual science 医学-眼科学

CiteScore

6.90

自引率

4.50%

发文量

339

审稿时长

1 months

期刊介绍： Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.