ArticleStem cell research & therapy2025
A single-cell transcriptomic atlas of human lens epithelium: identification and functional insights into lens stem/progenitor cells.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- mRNA and microRNA Expression Profile of Corneal and Conjunctival Impression Cytology Samples.Biology · 2026Article
- Lens aging and disease: Molecular mechanisms, functional consequences, and pharmacological implications.Progress in retinal and eye research · 2026Review
- Global challenges for lens and cataract research.Frontiers in ophthalmology · 2026Article
- Lens epithelial cells senescence in cataract pathogenesis and emerging therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Unanswered questions regarding the pathogenesis of late onset posterior capsular opacification.Frontiers in ophthalmology · 2025Review
- Cataract: Surgery first - is there still room for basic research?Advances in ophthalmology practice and researchReview
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Authors and funding
17 authors.
Funding
Abstract
backgroundThe 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.
methodsEight 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.
resultsSix 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, transcriptomic changes in LECs were observed, including weaker intercellular crosstalk and adhesion, and fewer TACs in S phase. Lens progenitor-like cells (LPLCs) were identified as a sub-population in early LECs and express ID1. In addition, pleiotrophin (PTN) signaling was prevalent at all differentiation stages, with a notable weakening of PTN signaling in aged LPLCs.
conclusionsThis study identified four subclasses of LECs within the human lens epithelium that follow a progressive staged development pathway from progenitor cells to mature LECs. TOP2A can serve as a biomarker for TAC in the lens, and LPLCs sustain their dedifferentiated state by expressing ID1. The aging process does not appear to alter cell population demographics, but significant alteration in gene expression profile is observed. Moreover, PTN signaling emerges as a crucial factor in lens homeostasis and represents a potential target for cataract drug development.
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