Systems Biology of Gene Regulatory Elements, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Department II of Internal Medicine and Center for Molecular Medicine Cologne.
J Am Soc Nephrol. 2018 Aug;29(8):2060-2068. doi: 10.1681/ASN.2018030238. Epub 2018 May 24.
Three different cell types constitute the glomerular filter: mesangial cells, endothelial cells, and podocytes. However, to what extent cellular heterogeneity exists within healthy glomerular cell populations remains unknown. We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli. Unsupervised clustering of nearly 13,000 single-cell transcriptomes identified the three known glomerular cell types. We provide a comprehensive online atlas of gene expression in glomerular cells that can be queried and visualized using an interactive and freely available database. Novel marker genes for all glomerular cell types were identified and supported by immunohistochemistry images obtained from the Human Protein Atlas. Subclustering of endothelial cells revealed a subset of endothelium that expressed marker genes related to endothelial proliferation. By comparison, the podocyte population appeared more homogeneous but contained three smaller, previously unknown subpopulations. Our study comprehensively characterized gene expression in individual glomerular cells and sets the stage for the dissection of glomerular function at the single-cell level in health and disease.
系膜细胞、内皮细胞和足细胞。然而,健康肾小球细胞群体中细胞异质性的程度仍不清楚。我们使用基于纳升级的高度平行转录谱分析来描述纯化的野生型小鼠肾小球的细胞含量。对近 13000 个单细胞转录组进行无监督聚类,鉴定出三种已知的肾小球细胞类型。我们提供了一个全面的肾小球细胞基因表达在线图谱,可使用交互式和免费提供的数据库进行查询和可视化。鉴定出所有肾小球细胞类型的新型标记基因,并得到了从人类蛋白质图谱获得的免疫组化图像的支持。内皮细胞的亚群聚类显示出一组表达与内皮细胞增殖相关的标记基因的内皮细胞。相比之下,足细胞群体似乎更加同质,但包含三个以前未知的较小亚群。我们的研究全面描述了单个肾小球细胞的基因表达,为在健康和疾病状态下在单细胞水平上解析肾小球功能奠定了基础。