Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor

Abstract

Lens epithelium, a fundamental biological structure pivotal for maintaining normal vision, can be disrupted, leading to the development of cataracts. The epithelial-mesenchymal transition has been proven to be the key factor of secondary cataract progression. However, the underlying mechanism of epithelial-mesenchymal transition in lens epithelial cells remains unclear. In this study, we conducted a comprehensive analysis and classification annotation of single-cell transcriptomic sequencing (scRNA-seq) data. This data was derived from fetal eye tissues of ages ranging from 9 to 23 weeks, sourced from our previously published research. Trajectory analysis showed a differentiation trend from epithelial cell to fiber cell. Furthermore, an integrative analysis of accessible-chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) data revealed that the transcription factor ATF6 may play a pivotal role in maintaining the homeostasis of lens epithelial cells. Subsequent in vitro experiments revealed that inhibition of ATF6 could alleviate epithelial-mesenchymal fibrosis by reducing STAT3 phosphorylation. Collectively, our study presents an atlas of lens epithelial cell development at the single-cell resolution, uncovering evidence that heightened ATF6 activity could potentially promote epithelial-mesenchymal transition in lens epithelial cells.

Keywords

• Activating transcription factor 6
• Cataract
• Epithelial-mesenchymal transition
• Fiber cell
• Lens epithelium
• Single-cell sequencing