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. 2020 Jun 11;11(6):645.
doi: 10.3390/genes11060645.

Relative Abundance of SARS-CoV-2 Entry Genes in the Enterocytes of the Lower Gastrointestinal Tract

Jaewon J Lee  1   2 , Scott Kopetz  3 , Eduardo Vilar  3   4 , John Paul Shen  3 , Ken Chen  5 , Anirban Maitra  1
Affiliations

Relative Abundance of SARS-CoV-2 Entry Genes in the Enterocytes of the Lower Gastrointestinal Tract

Jaewon J Lee et al. Genes (Basel). .

Abstract

There is increasing evidence of gastrointestinal (GI) infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We surveyed the co-expression of SARS-CoV-2 entry genes ACE2 and TMPRSS2 throughout the GI tract to assess potential sites of infection. Publicly available and in-house single-cell RNA-sequencing datasets from the GI tract were queried. Enterocytes from the small intestine and colonocytes showed the highest proportions of cells co-expressing ACE2 and TMPRSS2. Therefore, the lower GI tract represents the most likely site of SARS-CoV-2 entry leading to GI infection.

Keywords: COVID-19; SARS-CoV-2; gastrointestinal tract; scRNA-seq.

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Conflict of interest statement

A.M. receives royalties for a pancreatic cancer biomarker test from Cosmos Wisdom Biotechnology, and this financial relationship is managed and monitored by the UTMDACC Conflict of Interest Committee. A.M. is also listed as an inventor on a patent that has been licensed by Johns Hopkins University to Thrive Earlier Detection. E.V. has a consulting and advisory role with Janssen research and Development. The remaining authors disclose no conflicts.

Figures

Figure 1
Figure 1
Uniform manifold approximation and projection (UMAP) plots (left) of single-cell RNA-seq (scRNA-seq) data from (A) esophagus, (B) stomach, (C) pancreas, (D) small intestine and colon and (E) rectum; bubble plots showing expression levels of cell-type marker genes (middle) and bar plots depicting the distribution of different datasets in each cell type (right). EEC: Enteroendocrine cell, GMC: Antral basal gland mucous cell, PMC: Pit mucous cell, Prolif: Proliferative, TA: Transit-amplifying cell.
Figure 2
Figure 2
SARS-CoV-2 entry gene co-expression in cells of the gastrointestinal (GI) tract. (A) UMAP plots depicting cells that co-express ACE2 and TMPRSS2. (B) Bar plots depicting proportions of cell types in the GI tract that co-express ACE2 and TMPRSS2.
Figure 3
Figure 3
Co-expression of ACE2 and TMPRSS2 with TMPRSS4. (A) UMAP plots depicting cells that co-express ACE2, TMPRSS2, and TMPRSS4 in small intestine and colon/rectum. (B) Bar plots depicting proportions of cell types in the small intestine and colon/rectum that co-express ACE2, TMPRSS2, and TMPRSS4.
Figure 4
Figure 4
ACE2 co-regulatory networks in the lower gastrointestinal (GI) tract. Bar plots of top Gene Ontology (GO) biological process terms enriched in 321 genes that are positively correlated with ACE2 expression in (A) the small intestine and in (B) the colon/rectum. Vertical dashed line (red) represents significance threshold at false discovery rate (FDR) of 0.05.
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