Data Sheet 2_Single-cell transcriptomics reveals predominantly inflammatory endothelial cell responses and suppressed vascular repair in silicosis.pdf

IntroductionSilicosis is a progressive fibrotic lung disease without effective treatment options, and its pathogenesis remains incompletely understood, particularly the role of endothelial cells (ECs).
MethodsHere, we utilized single-cell RNA sequencing to characterize endothelial responses in lungs from silica-exposed mice.
ResultsWe identified two functionally distinct endothelial subpopulations: 1. An inflammatory EC subtype, exhibiting significantly increased abundance and characterized by high expression of neutrophil-recruiting factors such as Spp1 (osteopontin), CCL (C-C motif chemokine ligand), and ESAM (endothelial cell–selective adhesion molecule), suggesting active involvement in neutrophil influx and persistent inflammation. 2. A reparative EC subtype, marked by upregulation of angiogenesis and vascular repair pathways, which exhibited decreased abundance and functional suppression within the silicotic lung microenvironment.
DiscussionThese results indicate a pathological shift toward inflammation-amplifying endothelial cells and impaired reparative capacity during silicosis progression. Our findings provide new mechanistic insights into endothelial cell dysfunction in silicosis and highlight potential targets for therapeutic intervention.

引言：矽肺是一种进行性纤维化肺部疾病，目前尚无有效治疗方案，其发病机制仍未完全阐明，内皮细胞（endothelial cells, ECs）在其中发挥的作用尤其有待厘清。
方法：本研究采用单细胞RNA测序技术，对硅暴露小鼠肺部的内皮细胞应答特征进行了系统表征与分析。
结果：我们成功鉴定出两种功能迥异的内皮细胞亚群：1. 炎症型内皮细胞亚型：该亚型细胞丰度显著升高，以高表达中性粒细胞招募相关因子为核心特征，包括Spp1（骨桥蛋白）、CCL（C-C基序趋化因子配体）以及ESAM（内皮细胞选择性黏附分子），提示其积极参与中性粒细胞浸润与持续性炎症反应的发生发展。2. 修复型内皮细胞亚型：该亚型以血管生成与血管修复通路的上调为标志性特征，但在矽肺肺部微环境中细胞丰度降低且功能受到抑制。
讨论：上述研究结果表明，在矽肺进展过程中，内皮细胞向促炎症放大表型发生病理性转变，且自身修复能力受损。本研究的发现为矽肺内皮细胞功能障碍的发病机制提供了全新的研究见解，并明确了潜在的治疗干预靶点。