Cell-Type-Specific Complement Expression in the Healthy and Diseased Retina
Cell-Type-Specific Complement Expression in the Healthy and Diseased Retina
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DOI：
10.1016/j.celrep.2019.10.084
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发表时间：
2019-11-26
期刊：
影响因子：
8.8
通讯作者：
Grosche, Antje
中科院分区：
文献类型：
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作者：
Pauly, Diana;Agarwal, Divyansh;Grosche, Antje
补体失调是许多视网膜疾病的特征，但在细胞水平上的机制理解是有限的。考虑到关于哪些视网膜细胞表达补体的知识缺口，我们对类似于92，000个小鼠视网膜细胞进行了单细胞RNA测序，并在五种主要的纯化视网膜细胞类型中验证了我们的结果。我们发现了11种细胞类型中存在分布的细胞类型特异性补体表达的证据。值得注意的是，Muller细胞是补体激活剂c1、c3、c4和cfb的主要贡献者。视网膜色素上皮（RPE）主要表达cfh和末端补体成分，而cfi和cfp转录本在神经元中最丰富。衰老增强c1s，cfb，cfp和cfi的表达，而cfh的表达减少。短暂性视网膜缺血增加小胶质细胞、Muller细胞和RPE中的补体表达。总之，我们报告了鼠视网膜细胞类型的独特的补体表达特征，表明视网膜微环境中局部补体表达的精心策划的调节。
Complement dysregulation is a feature of many retinal diseases, yet mechanistic understanding at the cellular level is limited. Given this knowledge gap about which retinal cells express complement, we performed single-cell RNA sequencing on similar to 92,000 mouse retinal cells and validated our results in five major purified retinal cell types. We found evidence for a distributed cell-type-specific complement expression across 11 cell types. Notably, Muller cells are the major contributor of complement activators c1s, c3, c4, and cfb. Retinal pigment epithelium (RPE) mainly expresses cfh and the terminal complement components, whereas cfi and cfp transcripts are most abundant in neurons. Aging enhances c1s, cfb, cfp, and cfi expression, while cfh expression decreases. Transient retinal ischemia increases complement expression in microglia, Muller cells, and RPE. In summary, we report a unique complement expression signature for murine retinal cell types suggesting a well-orchestrated regulation of local complement expression in the retinal microenvironment.