周细胞
肌成纤维细胞
间质细胞
下调和上调
血管生成
细胞生物学
转录组
生物
细胞
糖尿病性视网膜病变
癌症研究
内皮干细胞
转染
细胞培养
基因表达
病理
医学
内分泌学
基因
纤维化
遗传学
糖尿病
体外
作者
Katia Corano-Scheri,Jeremy A. Lavine,Thomas Tedeschi,Benjamin R. Thomson,Amani A. Fawzi
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2023-11-02
卷期号:8 (23)
被引量:3
标识
DOI:10.1172/jci.insight.172062
摘要
The management of preretinal fibrovascular membranes, a devastating complication of advanced diabetic retinopathy (DR), remains challenging. We characterized the molecular profile of cell populations in these fibrovascular membranes to identify potentially new therapeutic targets. Preretinal fibrovascular membranes were surgically removed from patients and submitted for single-cell RNA-Seq (scRNA-Seq). Differential gene expression was implemented to define the transcriptomics profile of these cells and revealed the presence of endothelial, inflammatory, and stromal cells. Endothelial cell reclustering identified subclusters characterized by noncanonical transcriptomics profile and active angiogenesis. Deeper investigation of the inflammatory cells showed a subcluster of macrophages expressing proangiogenic cytokines, presumably contributing to angiogenesis. The stromal cell cluster included a pericyte-myofibroblast transdifferentiating subcluster, indicating the involvement of pericytes in fibrogenesis. Differentially expressed gene analysis showed that Adipocyte Enhancer-binding Protein 1, AEBP1, was significantly upregulated in myofibroblast clusters, suggesting that this molecule may have a role in transformation. Cell culture experiments with human retinal pericytes (HRP) in high-glucose condition confirmed the molecular transformation of pericytes toward myofibroblastic lineage. AEBP1 siRNA transfection in HRP reduced the expression of profibrotic markers in high glucose. In conclusion, AEBP1 signaling modulates pericyte-myofibroblast transformation, suggesting that targeting AEBP1 could prevent scar tissue formation in advanced DR.
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