The protein expression profile of ACE2 in human tissues

Feria Hikmet; Loren Méar; Mathias Uhlén; Cecilia Lindskog

The most commonly used experimental models for assessing the tropism and replication of viruses in humans include ex vivo cultures of human respiratory tissues, primary cells from the human respiratory system, or cell lines derived from the human respiratory system. The most commonly used cell line in such studies is A549, derived from an alveolar epithelial AT2 cell lung carcinoma 25 . To explore which cell lines that may be suitable experimental models for analysis of ACE2, we analyzed the expression levels based on RNA-seq in 64 different cell lines, as part of the Cell Atlas in the HPA 26 . Interestingly, the expression levels of ACE2 were below cut-off in all three cell lines derived from human lung, including A549, the immortalized bronchial epithelial cell line HBEC-KT, and the small cell lung carcinoma cell line SCLC-21H. The expression levels were below cutoff also in most other cell lines, however, low expression (<5 NX) was found in BEWO (metastatic choriocarcinoma), HaCaT (keratinocytes), Hep G2 (hepatocellular carcinoma), NB-4 (acute promyelocytic leukemia), RPMI-8226 (multiple myeloma), RT4 (urinary bladder) and SH-SY5Y (neuroblastoma). This suggests that none of the lung cell lines are appropriate models for studying the role of ACE2 in the human respiratory system. In the previous immunohistochemistry study by Hamming et al, the positivity of ACE2 in cells from A549 was presented as a confirmation of expression in AT2 cells. Due to the lack of expression on ACE2 in A549 on the mRNA level and the fact that the same study suggested expression in multiple other tissue locations neither confirmed by mRNA levels or by well-validated antibodies in the present investigation, it is therefore likely that the previously published positivity of ACE2 in A549 was due to off-target binding.