A molecular single-cell lung atlas of lethal COVID-19.
A molecular single-cell lung atlas of lethal COVID-19.
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致命新冠肺炎的分子单细胞肺部图谱
DOI：
10.1038/s41586-021-03569-1
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发表时间：
2021-07
期刊：
影响因子：
64.8
通讯作者：
Izar B
中科院分区：
文献类型：
--
作者：
Melms JC;Biermann J;Huang H;Wang Y;Nair A;Tagore S;Katsyv I;Rendeiro AF;Amin AD;Schapiro D;Frangieh CJ;Luoma AM;Filliol A;Fang Y;Ravichandran H;Clausi MG;Alba GA;Rogava M;Chen SW;Ho P;Montoro DT;Kornberg AE;Han AS;Bakhoum MF;Anandasabapathy N;Suárez-Fariñas M;Bakhoum SF;Bram Y;Borczuk A;Guo XV;Lefkowitch JH;Marboe C;Lagana SM;Del Portillo A;Tsai EJ;Zorn E;Markowitz GS;Schwabe RF;Schwartz RE;Elemento O;Saqi A;Hibshoosh H;Que J;Izar B
呼吸衰竭是严重SARS-CoV-2感染患者死亡的主要原因，但对肺组织水平的宿主反应知之甚少。在这里，我们对19名死于COVID-19并接受快速尸检的人和7名对照者的肺中约116，000个细胞核进行了单核RNA测序。综合分析确定了细胞组成、转录细胞状态和细胞间相互作用的实质性改变，从而为致死性COVID-19的生物学提供了深入了解。来自COVID-19患者的肺部高度发炎，异常激活的单核细胞衍生的巨噬细胞和肺泡巨噬细胞密集浸润，但T细胞反应受损。单核/巨噬细胞来源的白细胞介素-1 β和上皮细胞来源的白细胞介素-6是SARS-CoV-2感染与其他病毒和细菌性肺炎相比的独特特征。肺泡2型细胞采用炎症相关的瞬时祖细胞状态，未能完全转变为肺泡1型细胞，导致肺再生受损。此外，我们确定了最近描述的CTHRC 1+病理性成纤维细胞的扩增，其有助于COVID-19中迅速发生的肺纤维化。对蛋白质活性和配体-受体相互作用的推断确定了破坏有害回路的假定药物靶点。该图集能够解剖致命的COVID-19，可以为我们了解COVID-19幸存者的长期并发症提供信息，并为治疗开发提供重要资源。
Respiratory failure is the leading cause of death in patients with severe SARS-CoV-2 infection, but the host response at the lung tissue level is poorly understood. Here we performed single-nucleus RNA sequencing of about 116,000 nuclei from the lungs of nineteen individuals who died with COVID-19 and underwent rapid autopsy and seven control individuals. Integrated analyses identified substantial alterations in cellular composition, transcriptional cell states, and cell-to-cell interactions, thereby providing insight into the biology of lethal COVID-19. The lungs from individuals with COVID-19 were highly inflamed, with dense infiltration of aberrantly activated monocyte-derived macrophages and alveolar macrophages, but had impaired T cell responses. Monocyte/macrophage-derived interleukin-1β and epithelial cell-derived interleukin-6 were unique features of SARS-CoV-2 infection compared to other viral and bacterial causes of pneumonia. Alveolar type 2 cells adopted an inflammation-associated transient progenitor cell state and failed to undergo full transition into alveolar type 1 cells resulting in impaired lung regeneration. Furthermore, we identified expansion of recently described CTHRC1+ pathological fibroblasts contributing to rapidly ensuing pulmonary fibrosis in COVID-19. Inference of protein activity and ligand-receptor interactions identified putative drug targets to disrupt deleterious circuits. This atlas enables dissection of lethal COVID-19, may inform our understanding of long-term complications of COVID-19 survivors, and provides an important resource for therapeutic development.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
64.8
作者：
Gerbe F;Sidot E;Smyth DJ;Ohmoto M;Matsumoto I;Dardalhon V;Cesses P;Garnier L;Pouzolles M;Brulin B;Bruschi M;Harcus Y;Zimmermann VS;Taylor N;Maizels RM;Jay P
通讯作者：
Jay P
DOI：
10.1164/rccm.201911-2199oc
发表时间：
2020-12-15
影响因子：
24.7
作者：
Deprez, Marie;Zaragosi, Laure-Emmanuelle;Barbry, Pascal
通讯作者：
Barbry, Pascal
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
影响因子：
5.8
作者：
Angerer, Philipp;Haghverdi, Laleh;Buettner, Florian
通讯作者：
Buettner, Florian