Lu Huiping, Liu Xianyang, Zhou Qian, Li Ruonan, Zuo Hangjia, Hu Ke, Tian Meng, Wang Hong, Li Jianqiao, Li Na, Hou Shengping
The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China.
Genes Dis. 2025 Mar 22;12(6):101610. doi: 10.1016/j.gendis.2025.101610. eCollection 2025 Nov.
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 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.
晶状体上皮是维持正常视力的关键生物学结构，可能会受到破坏，从而导致白内障的发生。上皮-间质转化已被证明是继发性白内障进展的关键因素。然而，晶状体上皮细胞上皮-间质转化的潜在机制仍不清楚。在本研究中，我们对单细胞转录组测序（scRNA-seq）数据进行了全面分析和分类注释。这些数据来自于9至23周龄的胎儿眼组织，取材于我们之前发表的研究。轨迹分析显示了从上皮细胞到纤维细胞的分化趋势。此外，对可及染色质测序（scATAC-seq）和单细胞RNA测序（scRNA-seq）数据的综合分析表明，转录因子ATF6可能在维持晶状体上皮细胞的稳态中起关键作用。随后的实验表明，抑制ATF6可以通过降低STAT3磷酸化来减轻上皮-间质纤维化。总的来说，我们的研究提供了单细胞分辨率下的晶状体上皮细胞发育图谱，揭示了ATF6活性增强可能促进晶状体上皮细胞上皮-间质转化的证据。
