A human liver cell atlas reveals heterogeneity and epithelial progenitors
A human liver cell atlas reveals heterogeneity and epithelial progenitors
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DOI：
10.1038/s41586-019-1373-2
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发表时间：
2019-08-08
期刊：
影响因子：
64.8
通讯作者：
Gruen, Dominic
中科院分区：
文献类型：
--
作者：
Aizarani, Nadim;Saviano, Antonio;Gruen, Dominic
人体肝脏是一个重要的多功能器官。肝脏疾病的发病率正在上升，而治疗选择却有限。然而，人们对肝脏的细胞组成仍然知之甚少。在这里，我们对来自 9 名人类捐赠者的正常肝组织中的约 10,000 个细胞进行了单细胞 RNA 测序，以构建人类肝细胞图谱。我们的分析确定了以前未知的内皮细胞、库普弗细胞和肝细胞亚型，其中一些群体在转录组范围内分区。我们发现EPCAM（+）群体是异质的，包括肝细胞偏向性和胆管细胞群体以及TROP2（int）祖细胞群体，具有形成双能肝类器官的强大潜力。作为原理验证，我们使用图谱来揭示肝细胞癌细胞、人类肝细胞和移植到小鼠肝脏中的肝内皮细胞中发生的表型变化。我们的人类肝细胞图谱提供了强大的资源，使我们能够发现正常和患病肝脏中以前未知的细胞类型。
The human liver is an essential multifunctional organ. The incidence of liver diseases is rising and there are limited treatment options. However, the cellular composition of the liver remains poorly understood. Here we performed single-cell RNA sequencing of about 10,000 cells from normal liver tissue from nine human donors to construct a human liver cell atlas. Our analysis identified previously unknown subtypes of endothelial cells, Kupffer cells, and hepatocytes, with transcriptome-wide zonation of some of these populations. We show that the EPCAM(+) population is heterogeneous, comprising hepatocyte-biased and cholangiocyte populations as well as a TROP2(int) progenitor population with strong potential to form bipotent liver organoids. As a proof-of-principle, we used our atlas to unravel the phenotypic changes that occur in hepatocellular carcinoma cells and in human hepatocytes and liver endothelial cells engrafted into a mouse liver. Our human liver cell atlas provides a powerful resource to enable the discovery of previously unknown cell types in normal and diseased livers.