In-depth mining of single-cell transcriptome reveals the key immune-regulated loops in age-related macular degeneration

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Wencan Wang¹  Xiaoyan Lu¹  Youyuan Zhuang¹  Guosi Zhang¹  Peng Lin¹  Siyu Wang¹  Chong Chen¹  Hong Wang²  Liangde Xu²  Jianzhong Su³ 

[1] National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China;State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China;National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China;National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China;State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China;National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China;Center of Optometry International Innovation of Wenzhou, Eye Valley, Wenzhou, China;National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, China;State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China;National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China;Institute of PSI Genomics Co., Ltd., Wenzhou, China;

关键词: age-related macular degeneration (AMD);    single cell transcriptome sequencing (scRNA-seq);    cell communication;    regulon;    regulation loops;   

DOI  :  10.3389/fnmol.2023.1173123

 received in 2023-03-01, accepted in 2023-04-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionAge-related macular degeneration (AMD), an ever-increasing ocular disease, has become one of the leading causes of irreversible blindness. Recent advances in single-cell genomics are improving our understanding of the molecular mechanisms of AMD. However, the pathophysiology of this multifactorial disease is complicated and still an ongoing challenge. To better understand disease pathogenesis and identify effective targets, we conducted an in-depth analysis of the single-cell transcriptome of AMD.MethodsThe cell expression specificity of the gene (CESG) was selected as an index to identify the novel cell markers. A computational framework was designed to explore the cell-specific TF regulatory loops, containing the interaction of gene pattern signatures, transcription factors regulons, and differentially expressed genes.ResultsThree potential novel cell markers were DNASE1L3 for endothelial cells, ABCB5 for melanocytes, and SLC39A12 for RPE cells detected. We observed a notable change in the cell abundance and crosstalk of fibroblasts cells, melanocytes, schwann cells, and T/NK cells between AMD and controls, representing a complex cellular ecosystem in disease status. Finally, we identified six cell type related and three disease-associated ternary loops and elaborated on the robust association between key immune-pathway and AMD.DiscussionIn conclusion, this study facilitates the optimization of screening for AMD-related receptor ligand pathways and proposes to further improve the interpretability of disease associations from single-cell data. It illuminated that immune-related regulation paths could be used as potential diagnostic markers for AMD, and in the future, also as therapeutic targets, providing insights into AMD diagnosis and potential interventions.

【 授权许可】

Unknown   
Copyright © 2023 Wang, Lin, Wang, Zhang, Chen, Lu, Zhuang, Su, Wang and Xu.