ACE2 expression by colonic epithelial cells is associate with viral infection, immunity and energy metabolism

Wang et al

https://www.medrxiv.org/content/10.1101/2020.02.05.20020545v1

Summary

This study used colonic biopsies from 17 children (6 control, 6 colitis, 2 ulcerative colitis, 3 Crohn’s disease) to generate single cell RNA sequencing data and investigate colonic ACE2 expression, and the associated gene signature. Since ACE2 is believed to be a receptor for the spike protein of SARS-CoV2, and the virus has been found in faecal samples, understanding where it is expressed is important. ACE2 expression was limited to colonocytes, and associated with upregulation of genes associated with cellular and innate immunity, but downregulation of genes associated with humoral immunity.

Research highlights

1. Within the colon it is colonocytes that selectively express ACE2 during intestinal inflammation
2. ACE2 expression is positively correlated with genes associated with type I IFNs and T cells
3. ACE2 expression is negatively correlated with genes associated with B cell immunity

Research Impact

Larger disease cohorts could be used to investigate possible differences of ACE2 expression in colonocytes of different IBD subtypes.

Methodology

Single cell sequencing

Strengths and weaknesses of the paper

Strengths:

• Single cell analysis of colon biopsies shows that tuft, goblet, Paneth and enteroendocrine cells really do not seem to express ACE2, whereas colonocytes do.

Weaknesses:

• Low numbers of individuals (children – ages unclear) with varying diagnoses, which has not been accounted for in analyses. It seems that colonocytes express ACE2 regardless of disease state, but whether and how this varies in disease state is completely unclear.
• Colonocytes express ACE2 whereas subset colonocytes-BEST4 only express intermediate ACE2, but express the same levels of anti-viral and cytokine genes, which does not support their hypothesis that these are associated with ACE2.
• Correlation analysis is also unclear. If this has been performed in colonocytes then low expression of immunoglobulin is hardly unexpected. How this correlation has been performed is very unclear.
• Discussion focuses on possible treatments with anti-coagulation drugs. Whilst this is very interesting it does not relate to the data shown.