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World J Stem Cells. May 26, 2023; 15(5): 466-475
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.466
Single-cell RNA sequencing in cornea research: Insights into limbal stem cells and their niche regulation
Di Sun, Wei-Yun Shi, Sheng-Qian Dou
Di Sun, Wei-Yun Shi, Sheng-Qian Dou, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao 266000, Shandong Province, China
Di Sun, Sheng-Qian Dou, Qingdao Eye Hospital of Shandong First Medical University, Qingdao 266000, Shandong Province, China
Wei-Yun Shi, Eye Hospital of Shandong First Medical University, Jinan 250000, Shandong Province, China
Wei-Yun Shi, School of Ophthalmology, Shandong First Medical University, Qingdao 266000, Shandong Province, China
Author contributions: Dou SQ and Shi WY designed the report; Sun D collected the data and wrote the paper; Dou SQ and Shi WY reviewed and edited the manuscript; and all authors discussed the study’s results and provided important intellectual comments on the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sheng-Qian Dou, PhD, Associate Professor, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, No. 5 Yan’erdao Road, Qingdao 266000, Shandong Province, China. doushq@126.com
Received: December 30, 2022
Peer-review started: December 30, 2022
First decision: March 14, 2023
Revised: March 28, 2023
Accepted: April 17, 2023
Article in press: April 17, 2023
Published online: May 26, 2023
Abstract

The corneal epithelium is composed of stratified squamous epithelial cells on the outer surface of the eye, which acts as a protective barrier and is critical for clear and stable vision. Its continuous renewal or wound healing depends on the proliferation and differentiation of limbal stem cells (LSCs), a cell population that resides at the limbus in a highly regulated niche. Dysfunction of LSCs or their niche can cause limbal stem cell deficiency, a disease that is manifested by failed epithelial wound healing or even blindness. Nevertheless, compared to stem cells in other tissues, little is known about the LSCs and their niche. With the advent of single-cell RNA sequencing, our understanding of LSC characteristics and their microenvironment has grown considerably. In this review, we summarized the current findings from single-cell studies in the field of cornea research and focused on important advancements driven by this technology, including the heterogeneity of the LSC population, novel LSC markers and regulation of the LSC niche, which will provide a reference for clinical issues such as corneal epithelial wound healing, ocular surface reconstruction and interventions for related diseases.

Keywords: Cornea, Limbal stem cells, Single cell RNA sequencing, Heterogeneity, Novel markers, Niche regulation

Core Tip: Limbal stem cells (LSCs), a cell population that resides at the limbus in a highly regulated niche. With the advent of single-cell RNA sequencing, our understanding of LSC characteristics and their microenvironment has grown considerably. This review focuses on the current research on single cell sequencing in LSCs. We highlight the heterogeneity, novel specific markers and niche regulation of LSCs.