Ben Shuai, Ma Yan, Bai Yun, Zhang Qiuyang, Zhao Ya, Xia Jiao, Yao Mudi
Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.
National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China.
iScience. 2024 Feb 6;27(3):109145. doi: 10.1016/j.isci.2024.109145. eCollection 2024 Mar 15.
Inflammation-mediated crosstalk between neuroglial cells and endothelial cells (ECs) is a fundamental feature of many vascular diseases. Nevertheless, the landscape of inflammatory processes during diabetes-induced microvascular dysfunction remains elusive. Here, we applied single-cell RNA sequencing to elucidate the transcriptional landscape of diabetic retinopathy (DR). The transcriptome characteristics of microglia and ECs revealed two microglial subpopulations and three EC populations. Exploration of intercellular crosstalk between microglia and ECs showed that diabetes-induced interactions mainly participated in the inflammatory response and vessel development, with colony-stimulating factor 1 (CSF1) and CSF1 receptor (CSF1R) playing important roles in early cell differentiation. Clinically, we found that CSF1/CSF1R crosstalk dysregulation was associated with proliferative DR. Mechanistically, ECs secrete CSF1 and activate CSF1R endocytosis and the CSF1R phosphorylation-mediated MAPK signaling pathway, which elicits the differentiation of microglia and triggers the secretion of inflammatory factors, and subsequently foster angiogenesis by remodeling the inflammatory microenvironment through a positive feedback mechanism.
神经胶质细胞与内皮细胞（ECs）之间炎症介导的串扰是许多血管疾病的基本特征。然而，糖尿病诱导的微血管功能障碍期间炎症过程的情况仍不清楚。在此，我们应用单细胞RNA测序来阐明糖尿病视网膜病变（DR）的转录情况。小胶质细胞和内皮细胞的转录组特征揭示了两个小胶质细胞亚群和三个内皮细胞群体。对小胶质细胞与内皮细胞之间细胞间串扰的探索表明，糖尿病诱导的相互作用主要参与炎症反应和血管发育，集落刺激因子1（CSF1）和CSF1受体（CSF1R）在早期细胞分化中起重要作用。临床上，我们发现CSF1/CSF1R串扰失调与增殖性DR相关。从机制上讲，内皮细胞分泌CSF1并激活CSF1R内吞作用以及CSF1R磷酸化介导的MAPK信号通路，这引发小胶质细胞的分化并触发炎症因子的分泌，随后通过正反馈机制重塑炎症微环境来促进血管生成。
