Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor
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 epi...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2025-11-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225000996 |
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| author | Huiping Lu Xianyang Liu Qian Zhou Ruonan Li Hangjia Zuo Ke Hu Meng Tian Hong Wang Jianqiao Li Na Li Shengping Hou |
| author_facet | Huiping Lu Xianyang Liu Qian Zhou Ruonan Li Hangjia Zuo Ke Hu Meng Tian Hong Wang Jianqiao Li Na Li Shengping Hou |
| author_sort | Huiping Lu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-11ebf99bd2bc421cb7040d8efbfdafa1 |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-11ebf99bd2bc421cb7040d8efbfdafa12025-08-24T05:13:04ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-11-0112610161010.1016/j.gendis.2025.101610Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factorHuiping Lu0Xianyang Liu1Qian Zhou2Ruonan Li3Hangjia Zuo4Ke Hu5Meng Tian6Hong Wang7Jianqiao Li8Na Li9Shengping Hou10The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, ChinaThe First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, ChinaThe First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, ChinaThe First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, ChinaThe First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, ChinaThe First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, ChinaBeijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, ChinaDepartment of Ophthalmology, Qilu Hospital, Shandong University, Jinan, Shandong 250062, China; Corresponding author.Department of Laboratory Medicine, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Corresponding author.The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Chongqing Key Laboratory of Ophthalmology, Chongqing 400016, China; Chongqing Eye Institute, Chongqing 400016, China; Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China; Corresponding author. The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.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.http://www.sciencedirect.com/science/article/pii/S2352304225000996Activating transcription factor 6CataractEpithelial-mesenchymal transitionFiber cellLens epitheliumSingle-cell sequencing |
| spellingShingle | Huiping Lu Xianyang Liu Qian Zhou Ruonan Li Hangjia Zuo Ke Hu Meng Tian Hong Wang Jianqiao Li Na Li Shengping Hou Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor Genes and Diseases Activating transcription factor 6 Cataract Epithelial-mesenchymal transition Fiber cell Lens epithelium Single-cell sequencing |
| title | Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor |
| title_full | Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor |
| title_fullStr | Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor |
| title_full_unstemmed | Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor |
| title_short | Integrated analysis of single-cell RNA-seq and ATAC-seq in lens epithelial cells: Unveiling the role of ATF6 as a key transcription factor |
| title_sort | integrated analysis of single cell rna seq and atac seq in lens epithelial cells unveiling the role of atf6 as a key transcription factor |
| topic | Activating transcription factor 6 Cataract Epithelial-mesenchymal transition Fiber cell Lens epithelium Single-cell sequencing |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225000996 |
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