COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.
COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets.
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DOI：
10.1038/s41586-021-03570-8
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发表时间：
2021-07
期刊：
影响因子：
64.8
通讯作者：
Regev A
中科院分区：
文献类型：
--
作者：
Delorey TM;Ziegler CGK;Heimberg G;Normand R;Yang Y;Segerstolpe Å;Abbondanza D;Fleming SJ;Subramanian A;Montoro DT;Jagadeesh KA;Dey KK;Sen P;Slyper M;Pita-Juárez YH;Phillips D;Biermann J;Bloom-Ackermann Z;Barkas N;Ganna A;Gomez J;Melms JC;Katsyv I;Normandin E;Naderi P;Popov YV;Raju SS;Niezen S;Tsai LT;Siddle KJ;Sud M;Tran VM;Vellarikkal SK;Wang Y;Amir-Zilberstein L;Atri DS;Beechem J;Brook OR;Chen J;Divakar P;Dorceus P;Engreitz JM;Essene A;Fitzgerald DM;Fropf R;Gazal S;Gould J;Grzyb J;Harvey T;Hecht J;Hether T;Jané-Valbuena J;Leney-Greene M;Ma H;McCabe C;McLoughlin DE;Miller EM;Muus C;Niemi M;Padera R;Pan L;Pant D;Pe'er C;Pfiffner-Borges J;Pinto CJ;Plaisted J;Reeves J;Ross M;Rudy M;Rueckert EH;Siciliano M;Sturm A;Todres E;Waghray A;Warren S;Zhang S;Zollinger DR;Cosimi L;Gupta RM;Hacohen N;Hibshoosh H;Hide W;Price AL;Rajagopal J;Tata PR;Riedel S;Szabo G;Tickle TL;Ellinor PT;Hung D;Sabeti PC;Novak R;Rogers R;Ingber DE;Jiang ZG;Juric D;Babadi M;Farhi SL;Izar B;Stone JR;Vlachos IS;Solomon IH;Ashenberg O;Porter CBM;Li B;Shalek AK;Villani AC;Rozenblatt-Rosen O;Regev A
由SARS-CoV-2引起的COVID-19可导致急性呼吸窘迫综合征和多器官衰竭，但对其病理生理学知之甚少。在这里，我们生成了23个肺、16个肾、16个肝和19个心脏COVID-19尸检供体组织样本的单细胞图谱，以及14个肺供体的空间图谱。综合计算分析发现了肺上皮、免疫和间质区室的实质性重塑，并有证据表明组织再生失败的多种途径，包括有缺陷的肺泡2型分化和成纤维细胞以及推定的TP 63+肺内基底样祖细胞的扩增。病毒RNA在单核吞噬细胞和内皮肺细胞中富集，诱导特异性宿主程序。肺中的空间分析区分了有和没有病毒RNA的肺区域中的炎症宿主反应。对其他组织图谱的分析显示，COVID-19供体心脏组织中多种细胞类型的转录改变，并基于COVID-19 GWAS绘制了与疾病严重程度相关的细胞类型和基因。我们的基础数据集阐明了严重SARS-CoV-2感染对全身的生物学影响，这是迈向新治疗的关键一步。
COVID-19, caused by SARS-CoV-2, can result in acute respiratory distress syndrome and multiple-organ failure, but little is known about its pathophysiology. Here, we generated single-cell atlases of 23 lung, 16 kidney, 16 liver and 19 heart COVID-19 autopsy donor tissue samples, and spatial atlases of 14 lung donors. Integrated computational analysis uncovered substantial remodeling in the lung epithelial, immune and stromal compartments, with evidence of multiple paths of failed tissue regeneration, including defective alveolar type 2 differentiation and expansion of fibroblasts and putative TP63+ intrapulmonary basal-like progenitor cells. Viral RNAs were enriched in mononuclear phagocytic and endothelial lung cells which induced specific host programs. Spatial analysis in lung distinguished inflammatory host responses in lung regions with and without viral RNA. Analysis of the other tissue atlases showed transcriptional alterations in multiple cell types in COVID-19 donor heart tissue, and mapped cell types and genes implicated with disease severity based on COVID-19 GWAS. Our foundational dataset elucidates the biological impact of severe SARS-CoV-2 infection across the body, a key step towards new treatments.
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影响因子：
82.9
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.
通讯作者：
Ziegler, Carly G. K.
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影响因子：
5.9
作者：
Fernanda de Mello Costa M;Weiner AI;Vaughan AE
通讯作者：
Vaughan AE
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
20.3
作者：
Liu, Ta-Ming;Woyach, Jennifer A.;Johnson, Amy J.
通讯作者：
Johnson, Amy J.
影响因子：
3.5
作者：
Boesmueller, Hans;Traxler, Selina;Fend, Falko
通讯作者：
Fend, Falko