PRJNA714553: Single-cell transcriptome profiling reveals the suppressive role of retinal neurons in microglia activation under diabetes mellitus

Summary: Diabetic retinopathy, as one of the common complications of diabetes mellitus, is the leading cause of blindness in working-age population. The disease is characterized by damage to retinal vasculature, which is associated with the activation of retina microglial and chronic neurodegeneration. Previous studies have identified the effects of activated microglial on the retinal neurons, but how the microglial activation is regulated by the others is largely unknown. Here, we performed scRNA-seq on the retina of non-human primates with diabetes mellitus, and identified cell-type-specific molecular changes of the six major cell types. By identifying the ligand-receptor expression patterns among different cells, we established the interactome of the whole retina. The data showed that TNF-α signal mediated the activation of microglial through an autocrine manner. We found Muller and amacrine acted through SPP1 signaling and cone acted through TGFβ signaling, to inhibit the genes related to microglial activation. Our study is the first to profile cell-specific molecular changes and the cell-cell interactome of retina under diabetes mellitus, paving a way to dissect the cellular and molecular mechanisms underlying early-stage diabetic retinopathy.

Overall Design: scRNA-seq profiles of retina from control and diabetes mellitus.