Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.
复制标题
SARS-CoV-2进入基因跨组织和人口统计学的单细胞荟萃分析。
DOI：
10.1038/s41591-020-01227-z
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发表时间：
2021-03
期刊：
影响因子：
82.9
通讯作者：
Ziegler, Carly G. K.
中科院分区：
文献类型：
--
作者：
Muus, Christoph;Luecken, Malte D.;Eraslan, Gokcen;Sikkema, Lisa;Waghray, Avinash;Heimberg, Graham;Kobayashi, Yoshihiko;Vaishnav, Eeshit Dhaval;Subramanian, Ayshwarya;Smillie, Christopher;Jagadeesh, Karthik A.;Duong, Elizabeth Thu;Fiskin, Evgenij;Triglia, Elena Torlai;Ansari, Meshal;Cai, Peiwen;Lin, Brian;Buchanan, Justin;Chen, Sijia;Shu, Jian;Haber, Adam L.;Chung, Hattie;Montoro, Daniel T.;Adams, Taylor;Aliee, Hananeh;Allon, Samuel J.;Andrusivova, Zaneta;Angelidis, Ilias;Ashenberg, Orr;Bassler, Kevin;Becavin, Christophe;Benhar, Inbal;Bergenstrahle, Joseph;Bergenstrahle, Ludvig;Bolt, Liam;Braun, Emelie;Bui, Linh T.;Callori, Steven;Chaffin, Mark;Chichelnitskiy, Evgeny;Chiou, Joshua;Conlon, Thomas M.;Cuoco, Michael S.;Cuomo, Anna S. E.;Deprez, Marie;Duclos, Grant;Fine, Denise;Fischer, David S.;Ghazanfar, Shila;Gillich, Astrid;Giotti, Bruno;Gould, Joshua;Guo, Minzhe;Gutierrez, Austin J.;Habermann, Arun C.;Harvey, Tyler;He, Peng;Hou, Xiaomeng;Hu, Lijuan;Hu, Yan;Jaiswal, Alok;Ji, Lu;Jiang, Peiyong;Kapellos, Theodoros S.;Kuo, Christin S.;Larsson, Ludvig;Leney-Greene, Michael A.;Lim, Kyungtae;Litvinukova, Monika;Ludwig, Leif S.;Lukassen, Soeren;Luo, Wendy;Maatz, Henrike;Madissoon, Elo;Mamanova, Lira;Manakongtreecheep, Kasidet;Leroy, Sylvie;Mayr, Christoph H.;Mbano, Ian M.;McAdams, Alexi M.;Nabhan, Ahmad N.;Nyquist, Sarah K.;Penland, Lolita;Poirion, Olivier B.;Poli, Sergio;Qi, CanCan;Queen, Rachel;Reichart, Daniel;Rosas, Ivan;Schupp, Jonas C.;Shea, Conor, V;Shi, Xingyi;Sinha, Rahul;Sit, Rene, V;Slowikowski, Kamil;Slyper, Michal;Smith, Neal P.;Sountoulidis, Alex;Strunz, Maximilian;Sullivan, Travis B.;Sun, Dawei;Talavera-Lopez, Carlos;Tan, Peng;Tantivit, Jessica;Travaglini, Kyle J.;Tucker, Nathan R.;Vernon, Katherine A.;Wadsworth, Marc H.;Waldman, Julia;Wang, Xiuting;Xu, Ke;Yan, Wenjun;Zhao, William;Ziegler, Carly G. K.
ACE2和辅助蛋白(TMPRSS2，CTSL)是SARS-CoV-2进入细胞所必需的，它们的表达可能有助于揭示病毒的趋向性和对全身的影响。我们通过107项来自不同组织的单细胞RNA-SEQ研究评估了ACE2、TMPRSS2和CTSL的细胞类型特异性表达。ACE2、TMPRSS2和CTSL在鼻道、呼吸道和肺泡中的特定呼吸道上皮细胞亚群以及与新冠肺炎传播或病理相关的其他器官的细胞中共同表达。我们对来自228个个体的377个鼻腔、呼吸道和肺实质样本中的1,320,896个细胞进行了31项肺部scRNA-seq研究的荟萃分析。这揭示了年龄、性别和吸烟与ACE2、TMPRSS2和CTSL表达水平的细胞类型特异性关联。进入因子的表达随着年龄的增长而增加，在男性中，包括在呼吸道分泌细胞和肺泡AT2细胞中。鼻、肺和肠道组织中ACE2+TMPRSS2+细胞共有的表达程序包括可能介导病毒进入、关键免疫功能和上皮-巨噬细胞串扰的基因，如参与IL6、IL1、TNF和补体途径的基因。细胞类型特异的表达模式可能参与了新冠肺炎的发病机制，我们的工作强调了可能的分子途径用于治疗干预。
ACE2 and accessory proteases (TMPRSS2, CTSL) are needed for SARS-CoV-2 cellular entry, and their expression may shed light on viral tropism and impact across the body. We assess the cell type-specific expression of ACE2, TMPRSS2, and CTSL across 107 single-cell RNA-Seq studies from different tissues. ACE2, TMPRSS2, and CTSL are co-expressed in specific subsets of respiratory epithelial cells in the nasal passages, airways, and alveoli, and in cells from other organs associated with COVID-19 transmission or pathology. We performed a meta-analysis of 31 lung scRNA-seq 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 AT2 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 IL6, IL1, TNF and complement pathways. Cell type-specific expression patterns may contribute to COVID-19 pathogenesis , and our work highlights putative molecular pathways for therapeutic intervention.