The protein expression profile of ACE2 in human tissues

Feria Hikmet; Loren Méar; Mathias Uhlén; Cecilia Lindskog

Recently, several datasets presenting the expression of ACE2 in human lung based on single cell RNA-seq (scRNA-seq) have been published. This new platform for single cell analysis constitutes an important complement to the in situ localization by immunohistochemistry and thus provides an excellent tool in studies of transcript levels expected to be found in smaller subsets of cells in complex tissue samples. The data for ACE2 from multiple scRNA-seq datasets in human respiratory tract are however inconclusive. In Figure 3 , a summary of ACE2 expression in human lung based on three different publicly available scRNA-seq datasets is provided [16] [17] [18] with the transcriptomics expression in single cells of ACE2 and the surfactant protein SFTPA1. The data in all three datasets reveal that only a small fraction of the cells in lung express ACE2 at a low level, in contrast to the abundant expression of the surfactant protein in clusters representing AT2 cells. This is in contrast to other studies suggesting an enrichment in AT2 cells, although it should be noted that expression was often identified only in a very small fractions of the AT2 cells, often less than 1% 19, 20 . There are also other studies concluding that the ACE2 expression is considerably higher in other cells of the respiratory tract, such as ciliated or secretory cells 21, 22 , or in squamous epithelial cells of oral mucosa or esophagus 23, 24 . Similarly, in the recently published Human Cell Landscape (HCL) 16 , the expression levels of ACE2 were highest in cell types supporting the data from antibody-based immunohistochemistry from the HPA program, including jejunal and duodenal enterocytes, gallbladder epithelial cells, renal proximal tubules and testicular Sertoli cells. In the three samples from adult lung, the expression level was low, and no elevated expression was observed in AT2 cells as compared to secretory cells, macrophages or fibroblasts. In summary, the data from single cell transcriptomics studies reported here (Figure 3 ) supports the conclusion from the antibody-based immunohistochemistry analysis described above, suggesting that there are no or very low detectable protein levels of ACE2 in the lung.