A single-cell transcriptomic atlas of human lens epithelium: identification and functional insights into lens stem/progenitor cells

作者：Yuzhou Gu, Lu Chen, Shuying Chen, Yuhao Wu, Shengjie Hao, Feiyin Sheng, Jiali Yuan, Zhenwei Qin, Di Wu, Yu Han, Zengying Yao, Zhijian Chen, I. Michael Wormstone, Yibo Yu, Junbin Qian, Qiuli Fu, Ke Yao · 发表于：Stem Cell Research & Therapy · 年份：2025 · DOI：10.1186/s13287-025-04436-w · 被引用次数：9 · 研究领域：Connexins and lens biology、Intraocular Surgery and Lenses、Ophthalmology and Visual Impairment Studies

BACKGROUND: The existence of stem/progenitor cells in the lens epithelium has been demonstrated, but their identification remains challenging. Accurate identification requires advanced technologies and a comprehensive understanding of lens epithelial cell (LEC) subtypes, presenting a significant challenge in age-related cataract research. METHODS: Eight pairs of human donor lens epithelium samples were collected for single-cell RNA sequencing (scRNA-seq). This included four non-aged (< 65 years) and four aged (> 65 years) individuals. Subsequent analyses involved cell (sub)type characterization, trajectory inference, and cell-cell communication. Experimental validation was conducted through transcriptome sequencing and immunofluorescence on human lenses, lens organoids, rabbit regenerated lenses, mouse lenses, and cell lines. RESULTS: Six groups were identified via UMAP mapping of scRNA-seq data: four LECs, one lens fiber cells (LFCs), and one immune cells. One of the four LEC clusters exhibited a distinct gene expression profile and was identified as transient amplifying cells (TACs). TACs specifically express TOP2A and are localized at the lens equator. CytoTRACE analysis to the LEC and LFC data sets provided a differentiation trajectory. The TAC group was determined as stage 2 in the trajectory and LFCs last. The 3 sub groups were labelled early, mid and late LECs and corresponded to stage 1, 3 and 4 in the path. While cell population demographics remained stable with age,...