Coronavirus disease‐2019 (COVID‐19) is a global pandemic and caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which has resulted in millions of deaths worldwide. Reports denote SARS‐CoV‐2 uses angiotensin‐converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) as its primary entry point into the host cell. However, understanding the biology behind this viral replication, disease mechanism and drug discovery efforts are limited due to the lack of a suitable experimental model. Here, we used single‐cell RNA sequencing data of human organoids to analyze expressions of ACE2 and TMPRSS2, in addition to an array of RNA receptors to examine their role in SARS‐CoV‐2 pathogenesis. ACE2 is abundant in all organoids, except the prostate and brain, and TMPRSS2 is omnipresent. Innate immune pathways are upregulated in ACE2(+) cells of all organoids, except the lungs. Besides this, the expression of low‐density lipoprotein receptor is highly enriched in ACE2(+) cells in intestinal, lung, and retinal organoids, with the highest expression in lung organoids. Collectively, this study demonstrates that the organoids can be used as an experimental platform to explore this novel virus disease mechanism and for drug development.

中文翻译：

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人体类器官中 SARS-CoV-2 进入受体的单细胞 RNA 测序分析

冠状病毒病-2019 (COVID-19) 是一种全球大流行病，由严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 引起，已导致全球数百万人死亡。报告指出 SARS-CoV-2 使用血管紧张素转换酶 2 (ACE2)、跨膜丝氨酸蛋白酶 2 (TMPRSS2) 作为其进入宿主细胞的主要入口点。然而，由于缺乏合适的实验模型，了解这种病毒复制背后的生物学、疾病机制和药物发现努力是有限的。在这里，我们使用人类类器官的单细胞 RNA 测序数据来分析 ACE2 和 TMPRSS2 的表达，以及一系列 RNA 受体来检查它们在 SARS-CoV-2 发病机制中的作用。ACE2 在所有类器官中都很丰富，除了前列腺和大脑，TMPRSS2 无处不在。除肺外，所有类器官的 ACE2(+) 细胞中的先天免疫通路均上调。除此之外，低密度脂蛋白受体的表达在肠、肺和视网膜类器官的 ACE2(+) 细胞中高度富集，在肺类器官中表达最高。总的来说，这项研究表明，类器官可以用作探索这种新型病毒疾病机制和药物开发的实验平台。