The protein expression profile of ACE2 in human tissues - PubMed (original) (raw)

The protein expression profile of ACE2 in human tissues

Feria Hikmet et al. Mol Syst Biol. 2020 Jul.

Abstract

The novel SARS-coronavirus 2 (SARS-CoV-2) poses a global challenge on healthcare and society. For understanding the susceptibility for SARS-CoV-2 infection, the cell type-specific expression of the host cell surface receptor is necessary. The key protein suggested to be involved in host cell entry is angiotensin I converting enzyme 2 (ACE2). Here, we report the expression pattern of ACE2 across > 150 different cell types corresponding to all major human tissues and organs based on stringent immunohistochemical analysis. The results were compared with several datasets both on the mRNA and protein level. ACE2 expression was mainly observed in enterocytes, renal tubules, gallbladder, cardiomyocytes, male reproductive cells, placental trophoblasts, ductal cells, eye, and vasculature. In the respiratory system, the expression was limited, with no or only low expression in a subset of cells in a few individuals, observed by one antibody only. Our data constitute an important resource for further studies on SARS-CoV-2 host cell entry, in order to understand the biology of the disease and to aid in the development of effective treatments to the viral infection.

Keywords: ACE2; SARS-CoV-2; immunohistochemistry; respiratory system; transcriptomics.

© 2020 The Authors. Published under the terms of the CC BY 4.0 license.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1

Figure 1. ACE2 expression in human tissues based on transcriptomics

  1. Overview of the tissues and organs analyzed based on transcriptomics by the three independent consortia Human Protein Atlas (HPA), FANTOM5, and GTEx. In total, 16 organ systems (with several tissues comprising an organ system) were used to create a consensus normalized expression (defined as the unit NX) based on the expression levels of all three datasets.
  2. ACE2 gene expression summary in human tissues in 61 different tissues and cells in NX. Cutoff for what is regarded as expressed was set to 1.0 NX.

Figure 2

Figure 2. ACE2 expression in human tissues based on single‐cell transcriptomics

Dot plots summarizing the transcriptomics levels of ACE2 based on different scRNA‐seq datasets and tissues. Three different scales were used, in order to be able to compare percentages of cells expressing ACE2 both between and within tissue types. The size of the dots indicates the percentage of cells expressing ACE2 in respective cell type with a maximum of 60% (left column), 10% (middle column) and 1% (right column), and the color saturation corresponds to the average expression level. Plots were generated using Seurat package in R.

Figure 3

Figure 3. ACE2 protein expression in human tissues based on immunohistochemistry

  1. Summary of cell types positive for ACE2 using at least one antibody. Illustrations were in part adapted from https://biorender.com/.
  2. Details of cell type‐specific protein expression levels based on immunohistochemistry in tissues showing distinct immunohistochemical staining in at least one cell type using at least one antibody. Left panel: MAB933 (R&D Systems). Right panel: HPA000288 (Atlas Antibodies). Dot size: level of immunohistochemical staining based on staining intensity and fraction of positive cells. Asterisk: no ACE2 protein expression was observed in the standard TMA analysis, however ACE2 protein expression in lung AT2 cells was detected in an extended lung TMA cohort.

Figure 4

Figure 4. Cell type‐specific localization of ACE2 in human tissues based on immunohistochemistry

Representative images of 20 tissue types and histological structures stained on consecutive sections with immunohistochemistry using two antibodies targeting human ACE2 protein (brown), and counterstained with hematoxylin (blue). Most intense antibody staining was observed in microvilli of the intestinal tract and renal proximal tubules, in membranes of gallbladder epithelium, epididymis epithelium, testicular Sertoli cells and Leydig cells, a subset of glandular cells in seminal vesicle and cytoplasm of cardiomyocytes, with HPA000288 also staining the cardiac muscle fibers, while MAB933 only showed staining in a few cells. Distinct ACE2 staining for both antibodies was also present in cornea and conjunctiva of the eye, interlobular pancreatic ducts, as well as in placental villi, both in cytotrophoblasts, syncytiotrophoblasts, and also in extravillous trophoblasts, while placenta decidua was negative. ACE2 staining could be observed at the base of ciliated fallopian tube epithelium, however only for one of the antibodies. Note that ACE2 protein expression was less prominent in the crypts of the mucosal intestinal layer. ACE2 was also positive in endothelial cells and pericytes in several tissues, see fallopian tube, thyroid, parathyroid, adrenal gland, pancreas, and heart. Scale bar = 50 μm. Scale bar in dashed squares = 10 μm (Brunner = Brunner's gland, EVT = extravillous trophoblasts, endo = endothelial cells).

Figure EV1

Figure EV1. Human tissues with no ACE2 protein expression based on immunohistochemistry

Representative images of various human tissues and histological structures with no ACE2 protein expression, stained on consecutive sections with immunohistochemistry using two antibodies targeting the ACE2 protein and counterstained with hematoxylin (blue). Scale bar = 50 μm.

Figure 5

Figure 5. Cell type‐specific localization of ACE2 in human respiratory system based on immunohistochemistry

Representative images of human respiratory tissues, all stained on consecutive sections, with immunohistochemistry using two antibodies targeting human ACE2 protein (brown), and counterstained with hematoxylin (blue). Respiratory tissues were composed of different structures in nasal mucosa, bronchus, smaller bronchioles, and lung parenchyma. ACE2 staining could be observed at the base of ciliated cells in both nasal mucosa and bronchial epithelium (arrowheads). Rare ACE2 staining was present in a few alveolar cells (arrows). No staining was observed in nasal squamous epithelium, bronchioles, or submucosal glands in either tissue. Gender and age are shown for all individuals. Red and green colored squares mark the positions in the TMA cores shown as magnifications. Scale bar = 50 μm. Scale bar for images in dashed squares = 10 μm (re = respiratory; sq = squamous).

Figure 6

Figure 6. ACE2 expression in human tissues based on mass spectrometry and Western blot

  1. ACE2 protein abundance in different human tissues based on various studies processed by PaxDB, with expression levels presented as parts per million (ppm). The “Integrated” dataset corresponds to PaxDB estimation of average expression.
  2. ACE2 protein abundance in different human tissues from ProteomicsDB, with the median expression presented in log10(iBAQ).
  3. Western blot of ACE2 using five different human tissue lysates. For lung, two different lysates were used: one male (left) and one female (right).

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