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. 2021 Apr;236(4):2950-2958.
doi: 10.1002/jcp.30054. Epub 2020 Sep 17.

Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids

Rajasekaran Mahalingam  1 , Prakash Dharmalingam  2 , Abirami Santhanam  3 , Sivareddy Kotla  4 , Gangarao Davuluri  5 , Harry Karmouty-Quintana  6   7 , Guha Ashrith  8 , Rajarajan A Thandavarayan  6   8
Affiliations

Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids

Rajasekaran Mahalingam et al. J Cell Physiol. 2021 Apr.

Abstract

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.

Keywords: ACE2; COVID-19; SARS-CoV-2; TMPRSS2; human organoids; scRNA sequencing.

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Conflict of interest statement

The authors declare that there are no conflict of interests.

Figures

Figure 1
Figure 1
The expression profiles of ACE2 and TMPRSS2 in various organoids. The violin plot shows the ACE2 and TMPRSS2 expression in intestine, prostate, kidney, brain, retinal, and lung organoids. There is no ACE2 transcript observed in prostate and brain organoids. ACE2, angiotensin‐converting enzyme 2; TMPRSS2, transmembrane serine protease 2
Figure 2
Figure 2
The expression profile of curated scRNA receptors in ACE2(+) and ACE2(−) negative cells in various organoids. The dot plot shows the expression of multiple scRNA receptors transcript in the intestine, kidney, lung, and retinal organoids. ACE2, angiotensin‐converting enzyme 2; TMPRSS2, transmembrane serine protease 2
Figure 3
Figure 3
Immune specific enrichment profile for ACE2(+) and ACE2(−) negative cells in various organoids. The upregulation genes in the ACE2(+) cells are used for GO biological process enrichment analysis with specific immune‐related pathways in the intestine, kidney, and retinal organoids. ACE2, angiotensin‐converting enzyme 2; GO, gene ontology
See this image and copyright information in PMC

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