美国哈佛大学Christoph Muus等研究人员合作揭示了不同组织和人口中影响SARS-CoV-2进入细胞的因素。该项研究成果于2021年3月2日在线发表在《自然—医学》上。

研究人员在来自不同组织的107个单细胞RNA测序研究中评估了血管紧张素转换酶2（ACE2）和辅助蛋白酶（TMPRSS2和CTSL）的细胞类型特异性表达。ACE2、TMPRSS2和CTSL在鼻腔通道、气道和肺泡中呼吸道上皮细胞的特定亚群中，以及在与COVID-19传播或病理相关其他器官的细胞中共表达。

研究人员对来自228名个体的377例鼻、气道和肺实质样本中的1,320,896个细胞进行了31项肺单细胞RNA测序研究的荟萃分析。这揭示了年龄、性别和吸烟的细胞类型特异性关联与ACE2、TMPRSS2和CTSL的表达水平。细胞进入因子的表达随年龄和男性而增加，包括在气道分泌细胞和2型肺泡细胞中。ACE2⁺ TMPRSS2⁺细胞在鼻、肺和肠组织中共享的表达程序包括可能介导病毒进入、关键免疫功能和上皮-巨噬细胞交流的基因，例如与IL-6、IL-1、肿瘤坏死因子和补体途径。细胞类型特异性的表达模式可能与COVID-19的发病机理有关，这项研究重点介绍了治疗性干预的潜在分子途径。

据了解，SARS-CoV-2进入细胞需要ACE2、TMPRSS2和CTSL，它们的表达可能会阐明病毒的向性和对整个身体的影响。

附：英文原文

Title: Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics

Author: Christoph Muus, Malte D. Luecken, Gkcen Eraslan, Lisa Sikkema, Avinash Waghray, Graham Heimberg, Yoshihiko Kobayashi, Eeshit Dhaval Vaishnav, Ayshwarya Subramanian, Christopher Smillie, Karthik A. Jagadeesh, Elizabeth Thu Duong, Evgenij Fiskin, Elena Torlai Triglia, Meshal Ansari, Peiwen Cai, Brian Lin, Justin Buchanan, Sijia Chen, Jian Shu, Adam L. Haber, Hattie Chung, Daniel T. Montoro, Taylor Adams, Hananeh Aliee, Samuel J. Allon, Zaneta Andrusivova, Ilias Angelidis, Orr Ashenberg, Kevin Bassler, Christophe Bcavin, Inbal Benhar, Joseph Bergenstrhle, Ludvig Bergenstrhle, Liam Bolt, Emelie Braun, Linh T. Bui, Steven Callori, Mark Chaffin, Evgeny Chichelnitskiy, Joshua Chiou, Thomas M. Conlon, Michael S. Cuoco, Anna S. E. Cuomo, Marie Deprez, Grant Duclos, Denise Fine, David S. Fischer, Shila Ghazanfar, Astrid Gillich, Bruno Giotti, Joshua Gould, Minzhe Guo, Austin J. Gutierrez, Arun C. Habermann, Tyler Harvey, Peng He, Xiaomeng Hou, Lijuan Hu, Yan Hu, Alok Jaiswal, Lu Ji, Peiyong Jiang, Theodoros S. Kapellos, Christin S. Kuo, Ludvig Larsson, Michael A. Leney-Greene

Issue&Volume: 2021-03-02

Abstract: Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial–macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

DOI: 10.1038/s41591-020-01227-z

Source: https://www.nature.com/articles/s41591-020-01227-z