Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
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DOI：
10.1016/j.bbrc.2020.03.044
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发表时间：
2020-05-21
影响因子：
3.1
通讯作者：
Zhang, Zheng
中科院分区：
文献类型：
--
作者：
Qi, Furong;Qian, Shen;Zhang, Zheng
2019年12月在中国湖北武汉爆发的新型冠状病毒（SARS-CoV-2）已被宣布为全球公共卫生紧急事件。血管紧张素I转化酶2（ACE 2）是SARS冠状病毒2感染人体细胞的宿主受体。虽然ACE 2在肺、肝、胃、回肠、肾和结肠中表达，但其表达水平相当低，尤其是在肺中。SARS-CoV-2可能利用辅助受体/辅助蛋白作为ACE 2的配偶体来促进病毒的进入。为了确定潜在的候选者，我们探索了包括13种人体组织的119种细胞类型的单细胞基因表达图谱，并分析了51种已报道的RNA病毒受体和400种其他膜蛋白的单细胞共表达谱。与其他最近的报道一致，我们证实ACE 2主要表达于肺AT 2、肝胆管细胞、结肠结肠细胞、食管角质形成细胞、回肠EC、直肠EC、胃上皮细胞和肾近端小管。有趣的是，我们发现在13种人体组织中表现出与ACE 2最相似的表达模式的候选共受体都是肽酶，包括ANPEP、DPP 4和ENPEP。其中，ANPEP和DPP 4是已知的人冠状病毒的受体，提示ENPEP是人冠状病毒的另一种潜在受体。我们还进行了“CellPhoneDB”分析，以了解不同组织中Coy靶与其周围细胞之间的细胞串扰。我们发现，巨噬细胞经常通过趋化因子和吞噬信号与CoV靶点通信，突出了组织巨噬细胞在免疫防御和免疫发病机制中的重要性。(C)2020年深圳市第三人民医院\u0019 s。爱思唯尔公司出版
The new coronavirus (SARS-CoV-2) outbreak from December 2019 in Wuhan, Hubei, China, has been declared a global public health emergency. Angiotensin I converting enzyme 2 (ACE2), is the host receptor by SARS-CoV-2 to infect human cells. Although ACE2 is reported to be expressed in lung, liver, stomach, ileum, kidney and colon, its expressing levels are rather low, especially in the lung. SARS-CoV-2 may use co-receptors/auxiliary proteins as ACE2 partner to facilitate the virus entry. To identify the potential candidates, we explored the single cell gene expression atlas including 119 cell types of 13 human tissues and analyzed the single cell co-expression spectrum of 51 reported RNA virus receptors and 400 other membrane proteins. Consistent with other recent reports, we confirmed that ACE2 was mainly expressed in lung AT2, liver cholangiocyte, colon colonocytes, esophagus keratinocytes, ileum ECs, rectum ECs, stomach epithelial cells, and kidney proximal tubules. Intriguingly, we found that the candidate co-receptors, manifesting the most similar expression patterns with ACE2 across 13 human tissues, are all peptidases, including ANPEP, DPP4 and ENPEP. Among them, ANPEP and DPP4 are the known receptors for human CoVs, suggesting ENPEP as another potential receptor for human CoVs. We also conducted "CellPhoneDB" analysis to understand the cell crosstalk between Coy-targets and their surrounding cells across different tissues. We found that macrophages frequently communicate with the CoVs targets through chemokine and phagocytosis signaling, highlighting the importance of tissue macrophages in immune defense and immune pathogenesis. (C) 2020 Shenzhen Third People\u0019s Hospital. Published by Elsevier Inc.