José Ordovas-Montanes - May 27, 2020

José Ordovas-Montanes, PhD, Boston Children's Hospital, "SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human epithelial cells"

To uncover the factors that regulate ACE2, the SARS-CoV-2 entry receptor, Dr. Ordovas-Montanes worked with Alex K. Shalek, Carly Ziegler, Samuel Allon, Sarah Nyquist, researchers from the Human Cell Atlas Lung Biological Network, and other collaborators from around the world to investigate large single-cell RNA-sequencing datasets from human, primate, and mouse tissues. Of particular interest were barrier tissues—such as the skin, gut, and airway—and the epithelial cells associated with those tissues since his lab is interested in how different types of inflammation impact epithelial cells. They were interested in discerning which cell subsets were targeted by SARS-CoV-2 and what host factors are involved in regulating ACE2 expression. To answer this, their approach was to use existing sc-RNA-seq of datasets across health and disease, not COVID-19, from affected barrier tissues (nasal mucosa, lung, small intestine). In the lung, they found that TMPRSS2 was expressed in the Type II Pneumocytes. In illium, they found ACE2 and TMPRSS2 expression is associated with epithelial cells, particularly absorptive enterocytes. In the nasal mucosa, they found ACE2+TMPRSS2+ expression in the secretory goblet cells. Upon further analyzing the secretory goblet cells they found recurrent patterns of interferon-stimulated genes and then wondered whether interferon induced ACE2. Unexpectedly, they found that the gene encoding ACE2 is an interferon-stimulated gene in human upper airway epithelial cells, but not in mice, raising key implications for disease models and pre-clinical therapeutic development. Dr. Ordovas-Montanes also mentioned that ACE2 has a protective role during severe acute lung injury but SARS-CoV-2 seems to be inhibiting ACE2 function so something that is normally beneficial is, in this case, detrimental. Currently, they are partnering with the Chan Zuckerman Initiative to utilize sc-RNA-seq methods to see what they can learn from the supposedly resilient children infected with SARS-CoV-2 by sharing relevant basic and clinical pediatric data sets as rapidly as possible with the global scientific community.