Bioinformatic characterization of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2

Harlan Barker; Seppo Parkkila

Gene ontology investigations revealed interesting novel data on potential physiological roles of ACE2. The five most significant gene ontology terms included angiogenesis, blood vessel morphogenesis, vasculature development, cardiovascular system development, and blood vessel development. Our analysis of single cell RNA-Seq data suggested that ACE2 is positively, though weakly, expressed in the endothelial cells. In another study, ACE2 expression was previously detected in blood vessels (25), and a recent study showed that SARS-CoV-2 is capable of directly infecting blood vessel cells (11) . Based on the present finding angiogenesis/blood vessel morphogenesis may be considered a putative function for ACE2 in addition to its classical role as the key angiotensin-(1-7) forming enzyme (59) . The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.038752 doi: bioRxiv preprint dataset we studied included neither the AT2 nor secretory3 cells that have been recently shown positive for ACE2 (48) . The results suggest that SARS-CoV infection may target the cell types that are important for the protection of airway mucosa and their damage may lead to deterioration of epithelial cell function, finally leading to a more severe lung disease with accumulation of alveolar exudate and inflammatory cells and lung edema, the signs of pneumonia recently described in the lung specimens of two patients with COVID-19 infection (60) . Gene ontology analysis suggested that ACE2 is involved in angiogenesis/blood vessel morphogenesis processes in addition to its classical function in renin-angiotensin system. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.038752 doi: bioRxiv preprint Figure 2 . Immunohistochemical localization of ACE2 protein in selected human tissues. In the duodenum (A), the protein is most strongly localized to the apical plasma membrane of absorptive enterocytes (arrows). The goblet cells (arrowheads) show weaker apical staining. Intracellular staining is confined to the absorptive enterocytes. In the kidney (B), ACE2 shows prominent apical staining in the epithelial cells of the proximal convoluted tubules (arrows) and Bowman´s capsule epithelium (arrowheads). The distal convoluted tubules are negative (asterisk). The testis specimen (C) shows strong immunostaining in the seminiferous tubules (arrows) and interstitial cells (arrowheads). The lung sample (D) is negative. In the nasopharyngeal mucosa (E), ACE2 signal is very weak and only occasional epithelial cells show weak signals (arrows). Immunostained specimens were from Protein Expression Atlas (https://www.proteinatlas.org/). The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.13.038752 doi: bioRxiv preprint Figure 3 . Single cell RNA-Seq analysis of different cell types from the respiratory tract (mouse tracheal epithelium), derived from data from GEO dataset GSE103354 (37). Cell types were determined using markers as defined in the CellMarker database, as collected from the literature. ACE2 mRNA expression is shown for comparison in upper panel. UMAP dimensionality reduction plot was computed and visualized in ScanPy (40).