The World Health Organization declared the COVID-19 epidemic a public health emergency of international concern on March 11th, 2020, and the pandemic is rapidly spreading worldwide. COVID-19 is caused by a novel coronavirus SARS-CoV-2, which enters human target cells via angiotensin converting enzyme 2 (ACE2). We used a number of bioinformatics tools to computationally characterize ACE2 by determining its cell-specific expression in trachea, lung, and small intestine, derive its putative functions, and predict transcriptional regulation. The small intestine expressed higher levels of ACE2 mRNA than any other organ. By immunohistochemistry, duodenum, kidney and testis showed strong signals, whereas the signal was weak in the respiratory tract. Single cell RNA-Seq data from trachea indicated positive signals along the respiratory tract in key protective cell types including club, goblet, proliferating, and ciliary epithelial cells; while in lung the ratio of ACE2 -expressing cells was low in all cell types (<2.6%), but was highest in vascular endothelial and goblet cells. Gene ontology analysis suggested that, besides its classical role in the renin-angiotensin system, ACE2 may be functionally associated with angiogenesis/blood vessel morphogenesis. Using a novel tool for the prediction of transcription factor binding sites we identified several putative binding sites within two tissue-specific promoters of the ACE2 gene as well as a new putative short form of ACE2 . These include several interferon-stimulated response elements sites for STAT1, IRF8, and IRF9. Our results also confirmed that age and gender play no significant role in the regulation of ACE2 mRNA expression in the lung.
【초록키워드】 COVID-19, immunohistochemistry, ACE2, pandemic, angiotensin converting enzyme 2, bioinformatics, lung, angiotensin converting enzyme, binding site, Novel coronavirus, kidney, renin-angiotensin system, International, Ontology, epithelial cells, respiratory tract, public health emergency, Stat1, respiratory, expression, epithelial, predict, Protective, Testis, COVID-19 epidemic, Analysis, angiotensin, Trachea, ACE2 gene, transcription factor, cell types, cell type, target cells, Health Organization, goblet cells, target cell, World Health Organization, IRF9, endothelial, Regulation, Renin, Vascular, enzyme, ACE2 mRNA, duodenum, Gene ontology analysis, goblet, IRF8, novel coronavirus SARS-CoV-2, promoters, signal, small intestine, transcriptional regulation, functions, positive, organ, promoter, club, vessel, Cell, highest, classical, caused, include, indicated, expressed, suggested, age and gender, ciliary, interferon-stimulated response element, 【제목키워드】 SARS-CoV-2, angiotensin-converting enzyme 2, Bioinformatic, entry receptor,