A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors.
A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors.
复制标题
DOI：
10.1101/2020.05.08.084806
复制
发表时间：
2020-09-22
期刊：
影响因子：
8.8
通讯作者：
Feschotte, Cedric
中科院分区：
文献类型：
--
作者：
Singh, Manvendra;Bansal, Vikas;Feschotte, Cedric
为了预测人类冠状病毒的嗜性，我们使用来自广泛健康人体组织的单细胞RNA测序数据分析了28种SARS-CoV-2和冠状病毒相关受体和因子（SCARF）。SCARF包括促进和限制病毒进入的细胞因子。在成年器官中，小肠和结肠的肠细胞和杯状细胞、肾近端小管细胞和胆囊基底细胞似乎对SARS-CoV-2最宽容，这与临床数据一致。我们的分析还表明SARS-CoV-2感染的肺部、中枢神经系统和心脏的替代进入途径。我们预测精原细胞和前列腺内分泌细胞，但不是卵巢细胞，是高度容许SARS-CoV-2，这表明男性特有的脆弱性。胚胎和胎盘发育的早期阶段显示出中度感染风险。鼻上皮看起来像另一个战场，其特征是促进和限制因子的高表达以及SCARF表达的潜在年龄依赖性变化。最后，SCARF表达似乎在所检查的人类、黑猩猩和猕猴器官中广泛保守。我们的研究为冠状病毒生物学和病理学的研究建立了重要的资源。为了预测人类冠状病毒的嗜性，我们在各种健康人体组织中使用单细胞转录组学分析了28种SARS-CoV-2和冠状病毒相关受体和因子（SCARF）。SCARF包括促进和限制病毒进入的细胞因子。肠杯状细胞、肠上皮细胞和肾近端小管细胞对SARS-CoV-2表现出高度的容许性，这与临床数据一致。我们的分析还预测了肺部和脑部感染的非典型进入途径。精原细胞和前列腺内分泌细胞似乎也允许SARS-CoV-2感染，这表明男性特有的脆弱性。鼻上皮细胞内的亲病毒因子和抗病毒因子都高度表达，具有潜在的年龄依赖性变化，预测了冠状病毒感染的重要战场。我们的分析还表明，早期胚胎和胎盘发育有中度感染风险。最后，SCARF表达似乎在所检查的灵长类动物器官的子集中广泛保守。我们的研究为冠状病毒生物学和病理学的研究建立了资源。
To predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell RNA-sequencing data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of the small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear most permissive to SARS-CoV-2, consistent with clinical data. Our analysis also suggests alternate entry paths for SARS-CoV-2 infection of the lung, central nervous system, and heart. We predict spermatogonial cells and prostate endocrine cells, but not ovarian cells, to be highly permissive to SARS-CoV-2, suggesting male-specific vulnerabilities. Early stages of embryonic and placental development show a moderate risk of infection. The nasal epithelium looks like another battleground, characterized by high expression of both promoting and restricting factors and a potential age-dependent shift in SCARF expression. Lastly, SCARF expression appears broadly conserved across human, chimpanzee and macaque organs examined. Our study establishes an important resource for investigations of coronavirus biology and pathology.To predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell transcriptomics across various healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Intestinal goblet cells, enterocytes, and kidney proximal tubule cells appear highly permissive to SARS-CoV-2, consistent with clinical data. Our analysis also predicts non-canonical entry paths for lung and brain infections. Spermatogonial cells and prostate endocrine cells also appear to be permissive to SARS-CoV-2 infection, suggesting male-specific vulnerabilities. Both pro- and anti-viral factors are highly expressed within the nasal epithelium, with potential age-dependent variation, predicting an important battleground for coronavirus infection. Our analysis also suggests that early embryonic and placental development are at moderate risk of infection. Lastly, SCARF expression appears broadly conserved across a subset of primate organs examined. Our study establishes a resource for investigations of coronavirus biology and pathology.