以色列魏茨曼科学研究所Shalev Itzkovitz和葡萄牙葡京大学医学院Maria M. Mota共同合作，近期取得重要工作进展。他们研究绘制了疟原虫肝脏期的时空分辨单细胞图谱。这一研究成果2022年11月9日在线发表于《自然》杂志上。

研究人员结合单细胞RNA测序和单分子记录成像，以分区控制的方式表征啮齿动物疟疾寄生虫伯氏疟原虫ANKA的宿主和寄生虫的时间表达程序。研究人员发现不同区域寄生虫基因表达的差异，包括与铁和脂肪酸代谢相关的潜在协同适应方案。寄生虫在中心小叶周围区域发展得更快，研究人员识别出一个偏向于皮层周围的肝细胞亚群，该亚群存在流产性感染、疟原虫转录物水平降低和寄生性空泡破裂的特征。这些“流产肝细胞”，主要出现在高寄生虫接种物中，上调免疫募集和关键信号程序。

这一研究为在高空间分辨率下理解疟原虫感染的肝脏阶段提供了基础，并强调了寄生虫和宿主肝细胞的异质性行为。

据介绍，疟疾感染涉及一个强制性的、但临床上无症状的肝脏阶段。肝细胞在被称为小叶的重复单元中运行，沿着小叶轴表现出异质基因表达模式，但肝细胞分区在分子水平上对寄生虫发育的影响尚不清楚。

附：英文原文

Title: A spatiotemporally resolved single-cell atlas of the Plasmodium liver stage

Author: Afriat, Amichay, Zuzarte-Lus, Vanessa, Bahar Halpern, Keren, Buchauer, Lisa, Marques, Sofia, Chora, ngelo Ferreira, Lahree, Aparajita, Amit, Ido, Mota, Maria M., Itzkovitz, Shalev

Issue&Volume: 2022-11-09

Abstract: Malaria infection involves an obligatory, yet clinically silent liver stage1,2. Hepatocytes operate in repeating units termed lobules, exhibiting heterogeneous gene expression patterns along the lobule axis3, but the effects of hepatocyte zonation on parasite development at the molecular level remain unknown. Here we combine single-cell RNA sequencing4 and single-molecule transcript imaging5 to characterize the host and parasite temporal expression programmes in a zonally controlled manner for the rodent malaria parasite Plasmodium berghei ANKA. We identify differences in parasite gene expression in distinct zones, including potentially co-adaptive programmes related to iron and fatty acid metabolism. We find that parasites develop more rapidly in the pericentral lobule zones and identify a subpopulation of periportally biased hepatocytes that harbour abortive infections, reduced levels of Plasmodium transcripts and parasitophorous vacuole breakdown. These ‘abortive hepatocytes’, which appear predominantly with high parasite inoculum, upregulate immune recruitment and key signalling programmes. Our study provides a resource for understanding the liver stage of Plasmodium infection at high spatial resolution and highlights the heterogeneous behaviour of both the parasite and the host hepatocyte.

DOI: 10.1038/s41586-022-05406-5

Source: https://www.nature.com/articles/s41586-022-05406-5