A Single-Cell Transcriptome Atlas of the Mouse Glomerulus
A Single-Cell Transcriptome Atlas of the Mouse Glomerulus
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DOI：
10.1681/asn.2018030238
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发表时间：
2018-08-01
影响因子：
13.6
通讯作者：
Mueller, Roman-Ulrich
中科院分区：
文献类型：
--
作者：
Karaiskos, Nikos;Rahmatollahi, Mahdieh;Mueller, Roman-Ulrich
三种不同类型的细胞构成肾小球滤过器：系膜细胞、内皮细胞和足细胞。然而，在健康肾小球细胞群中存在何种程度的细胞异质性仍然未知。方法采用基于纳米微滴的高度平行转录谱分析方法来表征纯化野生型小鼠肾小球的细胞含量。结果近13,000个单细胞转录组的无监督聚类鉴定出三种已知的肾小球细胞类型。我们提供了肾小球细胞中基因表达的综合在线图谱，可以使用交互式和免费提供的数据库进行查询和可视化。所有肾小球细胞类型的新标记基因被鉴定出来，并得到来自人类蛋白质图谱的免疫组织化学图像的支持。内皮细胞亚群显示内皮细胞亚群表达与内皮细胞增殖相关的标记基因。相比之下，足细胞群体似乎更均匀，但包含三个较小的，以前未知的亚群体。结论本研究全面表征了单个肾小球细胞的基因表达，为在健康和疾病的单细胞水平上解剖肾小球功能奠定了基础。
Background 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.Methods We used nanodroplet-based highly parallel transcriptional profiling to characterize the cellular content of purified wild-type mouse glomeruli.Results 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.Conclusions 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.