SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells

SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells
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DOI:
10.15252/embj.20105114
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发表时间:
2020-04-17
期刊:
影响因子:
11.4
通讯作者:
Eils, Roland
Eils, Roland
中科院分区:
生物学1区
文献类型:
--
作者:
Lukassen, Soeren;Chua, Robert Lorenz;Eils, Roland

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影响人类呼吸系统的SARS-CoV-2大流行严重挑战了公共卫生,迫切要求我们增加对COVID-19发病机制的了解,特别是促进病毒感染和复制的宿主因素。据报道,SARS-CoV-2通过与ACE 2结合,然后通过TMPRSS 2引发而进入细胞。在这里,我们研究ACE 2和TMPRSS 2的表达水平和它们在肺组织(12个供体,39,778个细胞)和亚段支气管分支衍生的细胞(4个供体,17,521个细胞)中的细胞类型分布,分别通过单核和单细胞RNA测序。虽然TMPRSS 2在两种组织中均强烈表达,但在亚段支气管分支中,ACE 2主要以瞬时分泌细胞类型表达。有趣的是,这些短暂分化的细胞显示出与RHO GT3功能和病毒过程相关的途径的富集,这表明SARS-CoV-2感染的脆弱性增加。我们的数据为未来COVID-19感染和发病机制的研究提供了丰富的资源。
The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.