Single-cell combined with transcriptome sequencing to analyze changes in the cellular communication in trabecular meshwork cells in primary open-angle glaucoma
Objective To explore the changes in trabecular meshwork cell types and cellular communication patterns in primary open-angle glaucoma(POAG).Methods The POAG single-cell dataset GSE135337(including the trabecular meshwork samples of 3 cynomolgus macaque monkeys with POAG and 3 healthy cynomolgus macaque monkeys,data upda-ted to 2023)was downloaded from the Gene Expression Omnibus(GEO),two groups of samplesare named the POAG group and the control group.The downscaling,clustering,grouping,and visualization of data were performed using the Seurat package in R.The cellular communication pattern was analyzed by using the CellChat package in R to identify the differences in the cellular communication pattern between the POAG group and the control group.Meanwhile,the differen-tial gene analysis was performed based on the transcriptome sequencing(RNA-seq)dataset GSE27276(including the atrial horn tissue samples from 17 POAG patients and 19 healthy individuals,data updated to 2023)from the GEO to identify spe-cific cellular communication signaling changes.Results There were no significant differences in the cell types between the control group and the POAG group,including trabecular meshwork cells,macrophages,melanocytes,pericytes,Schlemm's canal cells,myelinating Schwann cells,nonmyelinating Schwann cells,smooth muscle cells,and vascular en-dothelial cells.There was a significant difference in the cellular communication intensity between the POAG group and the control group.The expression of macrophage migration inhibitory factor(MIF)-CD74,C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1),and HBB in the POAG group was significantly up-regulated compared with the control group,while the expression of secreted phosphoprotein 1(SPP1)-(ITGA8+ITGB1),SPP1-(IT-GA4+ITGB1),IGF2-IGF2R,CCL8-CCR1,and CCL8/26/24/2-ACKR2 in the POAG group was significantly down-regulated compared with the control group.The RNA-seq analysis results confirmed that the expression levels of HBB,HBD,HBA,and CD74 were higher in the POAG group than in the control group.Conclusion The up-regulation of MIF-CD74 and the down-regulation of SPP1-(ITGA8+ITGB1)and SPP1-(ITGA4+ITGB1)in trabecular meshwork tissues may participate in the fibrotic process,which may be a potential pathogenic mechanism of POAG.
万方数据
维普
