The protein expression profile of ACE2 in human tissues

Feria Hikmet; Loren Méar; Mathias Uhlén; Cecilia Lindskog

In line with the IWGAV recommendations, the HPA has introduced and implemented this concept for enhanced validation of antibodies 13 . The antibodies used in the HPA program for the immunohistochemical analysis of ACE2 have passed several of the criteria for enhanced antibody validation. The protein expression levels of two different antibodies showed high correlations with mRNA expression levels from three different datasets (HPA, GTEx and FANTOM5), thereby validating the antibodies using an orthogonal method. Furthermore, the cell type-specific localization of the protein expression across 78 different cell types was similar between the two independent antibodies. Of all 78 cell types evaluated, reliable expression was only observed in 10 cell types: microvilli of the duodenum, small intestine, colon and rectum, renal proximal tubules, in gallbladder epithelium, testicular Sertoli cells and Leydig cells, a subset of glandular cells in seminal vesicle, and in cardiomyocytes. (Figure 2 ). The cardiomyocyte staining was more diffuse and mainly cytoplasmic, while all other positive locations were as expected more prominent towards the plasma membrane. One antibody also showed positivity in a subset of apical membranes in liver bile ducts, while the other antibody was consistently negative in bile ducts of all three individuals. Due to the discrepancy between the antibodies, the staining in bile ducts for one of the antibodies should therefore be interpreted with caution, as it may represent off-target binding. No distinct expression confirmed by both antibodies could be found in any of the other analyzed cell types, including epithelial cells of the respiratory system, blood vessel endothelial cells, smooth muscle cells and fibroblasts. This immunohistochemistry analysis suggests a much more limited expression of the ACE2 in human tissues than previously suggested 11 , and the present body-wide expression profile shows a high correlation to different mRNA expression datasets.