System-wide transcriptome damage and tissue identity loss in COVID-19 patients.
System-wide transcriptome damage and tissue identity loss in COVID-19 patients.
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DOI：
10.1016/j.xcrm.2022.100522
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发表时间：
2022-02-15
期刊：
影响因子：
--
通讯作者：
Mason CE
中科院分区：
文献类型：
--
作者：
Park J;Foox J;Hether T;Danko DC;Warren S;Kim Y;Reeves J;Butler DJ;Mozsary C;Rosiene J;Shaiber A;Afshin EE;MacKay M;Rendeiro AF;Bram Y;Chandar V;Geiger H;Craney A;Velu P;Melnick AM;Hajirasouliha I;Beheshti A;Taylor D;Saravia-Butler A;Singh U;Wurtele ES;Schisler J;Fennessey S;Corvelo A;Zody MC;Germer S;Salvatore S;Levy S;Wu S;Tatonetti NP;Shapira S;Salvatore M;Westblade LF;Cushing M;Rennert H;Kriegel AJ;Elemento O;Imielinski M;Rice CM;Borczuk AC;Meydan C;Schwartz RE;Mason CE
冠状病毒病2019(新冠肺炎)临床表现的分子机制，以及它们与常见季节性流感病毒和其他肺损伤状态(如急性呼吸窘迫综合征)的区别仍不清楚。为了应对这些挑战，我们结合了646份临床鼻咽拭子和39份患者尸检组织的转录图谱，以确定全身转录组的变化对新冠肺炎的反应。然后，我们将这些数据与来自16个典型患者肺样本的357个组织切片的空间蛋白质和表达谱进行匹配，并识别严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染所造成的组织间隔性损伤，这显然是感染临床过程中不同病毒载量和组织类型特定表达状态的函数。总体而言，我们的发现揭示了所有组织中典型的细胞和转录途径的系统性破坏，这可以为后续研究提供信息，以对抗新冠肺炎的死亡率，并更好地了解致命性SARS-CoV-2和其他呼吸道感染的分子动力学。在所有器官中，成纤维细胞和免疫细胞群增加在新冠肺炎患者中所有器官特异的细胞类型和功能标记物在所有新冠肺炎组织类型中丢失肺间室身份丧失与SARS-CoV-2病毒载量新冠肺炎独一无二地破坏共生细胞类型簇(不同于IAV/ARDS)Park等人。报告由SARS-CoV-2、流感和跨越多个器官(心、肝、肺、肾和淋巴结)的细菌感染造成的系统范围的转录组损伤和组织身份丧失，并提供新冠肺炎在肺中的时空图景。
The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections. Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients Organ-specific cell types and functional markers are lost in all COVID-19 tissue types Lung compartment identity loss correlates with SARS-CoV-2 viral loads COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung.
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影响因子：
16.6
作者：
Corvol H;Blackman SM;Boëlle PY;Gallins PJ;Pace RG;Stonebraker JR;Accurso FJ;Clement A;Collaco JM;Dang H;Dang AT;Franca A;Gong J;Guillot L;Keenan K;Li W;Lin F;Patrone MV;Raraigh KS;Sun L;Zhou YH;O'Neal WK;Sontag MK;Levy H;Durie PR;Rommens JM;Drumm ML;Wright FA;Strug LJ;Cutting GR;Knowles MR
通讯作者：
Knowles MR
影响因子：
64.8
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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
通讯作者：
Regev A
影响因子：
6.4
作者：
Boumaza, Asma;Gay, Laetitia;Mege, Jean-Louis
通讯作者：
Mege, Jean-Louis
影响因子：
7.5
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Fang Z;Martin J;Wang Z
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Wang Z
影响因子：
2.7
作者：
Johnson, DR
通讯作者：
Johnson, DR