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Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas
Experimental Eye Research ( IF 3.4 ) Pub Date : 2021-08-06 , DOI: 10.1016/j.exer.2021.108718
Licheng Sun 1 , Ruonan Wang 1 , Guangyi Hu 1 , Huazhen Liu 1 , Kangjia Lv 1 , Yi Duan 1 , Ning Shen 1 , Jiali Wu 1 , Jing Hu 1 , Yujuan Liu 1 , Qihuang Jin 1 , Fang Zhang 1 , Xun Xu 1
Affiliation  

Diabetic retinopathy (DR) is an irreversible and progressive diabetic complication leading to visual impairment, even blindness. Due to the delicate and complicated structure of the retina, the pathology of DR has not been completely elucidated yet. We constructed a transcriptome atlas of >14,000 single cells from healthy and streptozotocin (STZ)-induced diabetic murine retinas to decipher pathological alterations of DR. We found four stress-inducible genes Cirbp, Rmb3, Mt1 and Mt2 commonly induced in most types of retinal cells. Bipolar cells were little affected on both number and gene expression. Diabetes increased expression of inflammatory factor genes in retinal microglia, and stimulated expression of immediate early genes (IEGs) in retinal astrocytes. A large number of genes were deregulated in diabetic vascular endothelial cells (ECs), and the differentially expressed genes were paired to the pathways functioning in metabolism, shear stress and vascular permeability. These pathways were mapped by more degregulated genes in a subpopulation of ECs specifically presented in diabetic retinas (diabetic retinal ECs, DRECs). Moreover, several inflammation pathways were activated in DRECs, and the most significant one is the IL-17 signaling pathway. According to the EC markers, DRECs were mainly capillary ECs, confirmed by immunofluorescent staining of S100a9, a target gene of the IL-17 signaling pathway. This study deciphered pathological alterations of DR, and provided clues for potential targets for DR therapy.



中文翻译:

单细胞 RNA 测序(scRNA-Seq)破译链脲佐菌素诱导的糖尿病视网膜病理改变

糖尿病视网膜病变 (DR) 是一种不可逆的、进行性的糖尿病并发症,可导致视力障碍,甚至失明。由于视网膜的精细和复杂的结构,DR的病理学尚未完全阐明。我们构建了来自健康和链脲佐菌素 (STZ) 诱导的糖尿病小鼠视网膜的 >14,000 个单细胞的转录组图谱,以破译 DR 的病理改变。我们发现四种应激诱导基因 Cirbp、Rmb3、Mt1 和 Mt2 通常在大多数类型的视网膜细胞中被诱导。双极细胞对数量和基因表达几乎没有影响。糖尿病增加了视网膜小胶质细胞中炎症因子基因的表达,并刺激了视网膜星形胶质细胞中即刻早期基因 (IEG) 的表达。大量基因在糖尿病血管内皮细胞(ECs)中失调,并且差异表达的基因与在代谢、剪切应力和血管通透性中起作用的途径配对。这些通路由糖尿病视网膜中特异性存在的 ECs 亚群(糖尿病视网膜 ECs,DRECs)中更多的失调基因定位。此外,DRECs 激活了多种炎症通路,其中最重要的是 IL-17 信号通路。根据EC标记物,DRECs主要是毛细血管ECs,通过IL-17信号通路的靶基因S100a9的免疫荧光染色证实。该研究破译了 DR 的病理改变,并为 DR 治疗的潜在靶点提供了线索。这些通路由糖尿病视网膜中特异性存在的 ECs 亚群(糖尿病视网膜 ECs,DRECs)中更多的失调基因定位。此外,DRECs 激活了多种炎症通路,其中最重要的是 IL-17 信号通路。根据EC标记物,DRECs主要是毛细血管ECs,通过IL-17信号通路的靶基因S100a9的免疫荧光染色证实。该研究破译了 DR 的病理改变,并为 DR 治疗的潜在靶点提供了线索。这些通路由糖尿病视网膜中特异性存在的 ECs 亚群(糖尿病视网膜 ECs,DRECs)中更多的失调基因定位。此外,DRECs 激活了多种炎症通路,其中最重要的是 IL-17 信号通路。根据EC标记物,DRECs主要是毛细血管ECs,通过IL-17信号通路的靶基因S100a9的免疫荧光染色证实。该研究破译了 DR 的病理改变,并为 DR 治疗的潜在靶点提供了线索。通过对 IL-17 信号通路的靶基因 S100a9 进行免疫荧光染色证实。该研究破译了 DR 的病理改变,并为 DR 治疗的潜在靶点提供了线索。通过对 IL-17 信号通路的靶基因 S100a9 进行免疫荧光染色证实。该研究破译了 DR 的病理改变,并为 DR 治疗的潜在靶点提供了线索。

更新日期:2021-08-07
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