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Updated: May 24, 2025
An Epithelial Abrasion Model for Studying Corneal Wound Healing
Published on: December 29, 2021
Single-Cell Multiomics Analysis of Early Wound Response Programs in the Mouse Corneal Epithelium
Zhao-Jing Lu1,2, Jin-Guo Ye1, Jing-Ni Li1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Purpose:
Wound healing is crucial for restoring homeostasis in living organisms. Although wound response mechanisms have been studied extensively, the gene regulatory programs involved remain to be elucidated. Here, we used single-cell RNA sequencing (RNA-seq) and ATAC sequencing (ATAC-seq) analysis to profile the regulatory landscape of mouse corneal epithelium in early wound response.
Methods:
We used our previously published single-cell data sets of homeostatic adult mouse corneal epithelium as the unwounded group. The wounded group data sets were obtained by sequencing the epithelium after an annular epithelial wound. Following the integration of the relevant data sets, the Seurat and ArchR packages were employed for single-cell RNA-seq and single-cell ATAC-seq data processing and downstream analysis, respectively. The Monocle 2 was used for pseudo-time analysis, CellChat for intercellular communication analysis, and pySCENIC for analyzing transcription factors. The expression of key genes was validated via immunofluorescence staining and quantitative real-time PCR.
Results:
Our data show that the number of cell type-specific genes decreases and the number of common transcriptional responses increases in early wound response. Concurrently, we find that the chromatin accessibility landscape undergoes significant changes across all epithelial cell types and that the wound-induced open regions are similarly distributed across the genome. Motif enrichment analysis shows that Fosl1/AP-1 binding site is highly enriched among the opened regions. However, by assessing the correlation between changes in chromatin accessibility and gene expression, we observe that only a small subset of wound-induced genes shows a high correlation with the accessibility of nearby chromatin.
Conclusions:
Our study provides a detailed single-cell landscape for transcriptomic and epigenetic changes in mouse corneal epithelium during early wound response, which improved our understanding of the mechanisms of wound healing.
