单细胞分析人类肾脏和膀胱中血管紧张素转化酶 2 的表达，揭示了 2019 年新型冠状病毒感染的潜在途径。

Single-cell analysis of angiotensin-converting enzyme II expression in human kidneys and bladders reveals a potential route of 2019 novel coronavirus infection.

机构信息

Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

Department of Bioinformatics and Data Science, Singleron Biotechnologies, Nanjing, Jiangsu 210032, China.

出版信息

Chin Med J (Engl). 2021 Apr 20;134(8):935-943. doi: 10.1097/CM9.0000000000001439.

DOI:10.1097/CM9.0000000000001439

PMID:33879756

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8078266/

Abstract

BACKGROUND

Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.

METHODS

We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.

RESULTS

Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.

CONCLUSION

This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

摘要

背景

自 2019 年以来，一种名为 2019 年新型冠状病毒（2019-nCoV）的新型冠状病毒在全球范围内出现。除发热和呼吸道并发症外，在少数冠状病毒病 2019 患者中还观察到急性肾损伤。此外，根据最近的发现，该病毒已在尿液中检测到。血管紧张素转换酶 II（ACE2）被提议作为 2019-nCoV 进入的受体，与严重急性呼吸综合征相同。本研究旨在探讨肾脏损伤的可能原因以及 2019-nCoV 在泌尿系统感染的潜在途径。

方法

我们使用已发表的肾脏和膀胱细胞图谱数据和内部生成的新的独立肾脏单细胞 RNA 测序数据，评估健康肾脏和膀胱中所有细胞类型中 ACE2 基因的表达。首先生成 ACE2 与所有其他基因之间的 Pearson 相关系数。然后，将 r 值大于 0.1 且 P 值小于 0.01 的基因视为与 ACE2 具有显著共表达的基因。

结果

我们的结果表明 ACE2 在肾脏近端小管（PT）细胞的所有亚型中均有丰富表达。在三个已发表的肾脏细胞图谱数据集的近端卷曲管细胞、PT 细胞和近端直小管细胞中，分别有 5.12%、5.80%和 14.38%表达 ACE2。此外，在我们自己的两个健康肾脏样本中，分别在近端卷曲管、PT 和近端直小管细胞中也证实了 ACE2 的表达，比例分别为 12.05%、6.80%和 10.20%。对于来自三个膀胱样本的公共数据分析，ACE2 在膀胱上皮细胞中的表达较低但可检测到。中间细胞和伞细胞中分别只有 0.25%和 1.28%表达 ACE2。