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

Mahalingam, Rajasekaran; Dharmalingam, Prakash; Santhanam, Abirami; Kotla, Sivareddy; Davuluri, Gangarao; Karmouty‐Quintana, Harry; Ashrith, Guha; Thandavarayan, Rajarajan A.

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.