Single-cell RNA sequencing reveals the complex cellular niche of pterygium

Abstract

Purpose: Pterygium is a vision-threatening conjunctival fibrovascular degenerated disease with a high global prevalence up to 12 %, while no absolute pharmacotherapy has been applied in clinics. In virtue of single-cell RNA sequencing (scRNA-seq) technique, our study investigated underlying pathogeneses and potential therapeutic targets of pterygium from the cellular transcriptional level.

Methods: A total of 45605 cells from pterygium of patients and conjunctiva of normal controls (NC) were conducted with scRNA-seq, and then analyzed via integrated analysis, pathway enrichment, pseudotime trajectory, and cell-cell communications. Besides, immunofluorescence and western blot were performed in vivo and in vitro to verify our findings.

Results: In brief, 9 major cellular types were defined, according to canonical markers. Subsequently, we further determined the subgroups of each major cell lineages. Several newly identified cell sub-clusters could promote pterygium, including immuno-fibroblasts, epithelial mesenchymal transition (EMT)-epithelial cells, and activated vascular endothelial cells (activated-vEndo). Besides, we also probed the enrichment of immune cells in pterygium. Particularly, macrophages, recruited by ACKR1⁺activated-vEndo, might play an important role in the development of pterygium by promoting angiogenesis, immune suppression, and inflammation.

Conclusion: An intricate cellular niche was revealed in pterygium via scRNA-seq analysis and the interactions between macrophages and ACKR1⁺ activated-vEndo might be the key part in the development of pterygia.

Keywords: Conjunctiva; Immune cells; Pterygium; Single-cell RNA sequencing.