德国Max Planck免疫生物学和表观遗传学研究所Dominic Grün研究组与法国斯特拉斯堡大学Thomas F. Baumert研究团队合作，绘制出完整的人类肝细胞图谱，并应用于显示异质性和上皮祖细胞。相关论文刊登在2019年8月8日出版的《自然》上。

科学家们总共招募了9名人类志愿者，其中有健康人，也有罹患肝脏疾病的病人。从这些志愿者中，研究人员们一共分析了超过10000个肝脏细胞，并进行了单细胞RNA测序，以了解每个细胞中不同基因的表达情况。确定了以前未知的内皮细胞、库普弗细胞和肝细胞亚型，其中一些人群具有转录组范围的分区。值得一提的是，研究发现EPCAM+群体是异质性的，包括肝细胞偏倚和胆管细胞群体，以及具有形成双效肝类器官潜能的前体细胞群体。作为原理验证，该图谱被用来揭示肝细胞癌细胞和人肝细胞、以及移植到小鼠肝脏中的肝脏内皮细胞中发生的表型变化。

据悉，人类的肝脏是一个重要的多功能器官。肝脏疾病的发病率正在逐年上升，然而目前相关的治疗方案却非常有限，对肝脏细胞的组成也知之甚少。人类肝细胞图谱的问世为学界提供了强大的资源，可以在正常和患病的肝脏中发掘未知的细胞类型。
 

附：英文原文

Title: A human liver cell atlas reveals heterogeneity and epithelial progenitors

Author: Nadim Aizarani, Antonio Saviano, Sagar, Laurent Mailly, Sarah Durand, Josip S. Herman, Patrick Pessaux, Thomas F. Baumert, Dominic Grn

Issue&Volume: Volume 572 Issue 7768

Abstract: 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 TROP2int 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.

DOI: 10.1038/s41586-019-1373-2

Source: https://www.nature.com/articles/s41586-019-1373-2