TY - JOUR
T1 - Single-cell RNA sequencing analysis of SARS-CoV-2 entry receptors in human organoids
AU - Mahalingam, Rajasekaran
AU - Dharmalingam, Prakash
AU - Santhanam, Abirami
AU - Kotla, Sivareddy
AU - Davuluri, Gangarao
AU - Karmouty-Quintana, Harry
AU - Ashrith, Guha
AU - Thandavarayan, Rajarajan A.
N1 - Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - ACE2
KW - COVID-19
KW - SARS-CoV-2
KW - TMPRSS2
KW - human organoids
KW - scRNA sequencing
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U2 - 10.1002/jcp.30054
DO - 10.1002/jcp.30054
M3 - Article
C2 - 32944935
AN - SCOPUS:85091037811
SN - 0021-9541
VL - 236
SP - 2950
EP - 2958
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 4
ER -