Single-cell RNA sequencing analysis of SARS-CoV-2 conventional and
moonlighting receptors in human organoids
Abstract
Background and Purpose: Lack of suitable experimental models hinders
SARS-CoV-2 research. Reports denote SARS-CoV-2 uses ACE2, TMPRSS-2 as
its primary receptors. However, SARS-CoV-2 clinical symptoms were also
related to organs with poor or no expressions of primary receptors.
Hence, using single-cell RNA sequencing data of human organoids, we
analyzed expression levels of primary receptors and array of RNA
receptors for their involvement in SARS-CoV-2 pathogenesis. Experimental
Approach: From the gene expression omnibus (GEO) or array express
database, normalized cell counts of human intestine coventional,
intestine improved, prostate, kidney morizane, kidney takasato, brain,
retinal, lung organoids were obtained. Individual cell types, RNA
receptor expressions in ACE2 (+) and ACE2(-) cells were analyzed. Using
immune enrichment analysis, immune pathway activation in ACE2(+) and
ACE2(-) cells were determined. Key Results: ACE2 expression is abundant
in all organoid, except prostate and brain, while TMPRSS2 is
omnipresent. Innate immune component pathways are upregulated in ACE2
(+) cells in all organoids, except lung. Besides, expression of
low-density lipoprotein receptor (LDLR) is highly enriched in ACE2 (+)
cells in intestinal (conventional and improved), lung, and retinal
organoids, with highest expression in lung organoids. Other than primary
receptors, LDLR and HDLR might also exert crucial role SARS-CoV-2
pathogenesis. Conclusion and Implications: Mimicing Invivo niche, with
array of cell types expressing primary and RNA receptors, immune
pathways activation, human organoids will be suitable model for rapid
SARS-CoV-2 translational research. Other than ACE2 and TMPRSS2, LDLR and
HDLR with moonlighting functions can be useful targets in SARS-CoV-2
clinical management.