Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution.
Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution.
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DOI：
10.1016/j.isci.2021.102738
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发表时间：
2021-07-23
期刊：
影响因子：
5.8
通讯作者：
Bryson BD
中科院分区：
文献类型：
--
作者：
Overholt KJ;Krog JR;Zanoni I;Bryson BD
严重的 COVID-19 伴随着肺部和外周的严重免疫失调，两个区室的免疫细胞都会导致全身性窘迫。在严重疾病期间，肺部和血液的免疫细胞进入相似或不同病理状态的程度仍不清楚。在这里，我们利用 96 个公开的单细胞 RNA 测序数据集来阐明严重至危重 COVID-19 在转录表达、生物途径和配体受体信号网络水平上的常见和特定特征。通过将重症患者与轻度健康供体进行比较，我们发现了区室和一组核心的同向调节表面标记物之间不同的差异基因表达特征。大多数严重程度丰富的途径是相同的，而 TNF 和干扰素反应是两极分化的。严重程度特异性的配体受体网络似乎在两个区室中具有不同的活性。总的来说，我们的结果描述了严重的 COVID-19 期间的微妙反应，其中区室在决定免疫细胞的病理状态方面发挥着作用。来自严重、轻度至中度和健康供体的 COVID-19 96 个单细胞公共数据集中的肺和血液免疫细胞区室的转录组比较 严重程度特异性细胞表面标记和区室之间共享的通路 区室内部和之间的推定配体-受体信号传导对话 病理生理学；免疫学；复杂系统生物学；转录组学
Severe COVID-19 is accompanied by rampant immune dysregulation in the lung and periphery, with immune cells of both compartments contributing to systemic distress. The extent to which immune cells of the lung and blood enter similar or distinct pathological states during severe disease remains unknown. Here, we leveraged 96 publicly available single-cell RNA sequencing datasets to elucidate common and compartment-specific features of severe to critical COVID-19 at the levels of transcript expression, biological pathways, and ligand-receptor signaling networks. Comparing severe patients to milder and healthy donors, we identified distinct differential gene expression signatures between compartments and a core set of co-directionally regulated surface markers. A majority of severity-enriched pathways were shared, whereas TNF and interferon responses were polarized. Severity-specific ligand-receptor networks appeared to be differentially active in both compartments. Overall, our results describe a nuanced response during severe COVID-19 where compartment plays a role in dictating the pathological state of immune cells. Transcriptomic comparisons of lung and blood immune cell compartments in COVID-19 96 single-cell public datasets from severe, mild-to-moderate, and healthy donors Severity-specific cell surface markers and pathways shared between compartments Putative ligand-receptor signaling dialogs within and between compartments Pathophysiology; Immunology; Complex system biology; Transcriptomics
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
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作者：
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