scRNA-seq (10x) from pediatric human terminal ileum show ACE2 and TMPRSS2 are most enriched within GSTA1+MGST3+ absorptive enterocytes.

We collected single-cell RNA-seq data from biopsies of the human terminal ileum (epithelial and lamina propria) across 13 children diagnosed with functional gastrointestinal disease (without inflammation) and ranging in age 6-18 years old. Ileal absorptive epithelial cells appear significantly enriched for ACE2 and TMPRSS2 expression. Furthermore, we identify a subset (888 cells, ~6.5% of epithelial cells) which co-express both genes. By identifying rare co-expressing cells, we are able to perform differential expression testing and GO-term enrichment to highlight putative biological functions enriched within these cells such as metabolic processes and catalytic activity. Finer-grained clustering revealed a specific subset of ileal absorptive cells, marked by GSTA1, MGST3, APOA1, APOA4, ADH1C and encompassing some crypt based absorptive cells, contained the most significantly enriched ACE2 and TMPRSS2 expression. As symptoms of COVID-19 have been reported to include gastrointestinal involvement, we suggest these cells may be principal targets of viral entry.

Note that because this is a pre-publication dataset we are only reporting genes for absorptive and crypt based enterocytes (i.e., the cell types where we detect ACE2 and TMPRSS2). The entirety of the dataset will be released at publication of the primary study.

Analysis of this data to evaluate expression of COVID-19 receptor ACE2 and protease TMPRSS2 are described in the following manuscript: https://www.cell.com/cell/fulltext/S0092-8674(20)30500-6

And summarized here: http://shaleklab.com/resource/covid-19-resources/

Contributors: Betty Zheng*, Alison Yu*, Benjamin Doran*, Kayla Cribben, Ryan Fleming, Alexandria Narayan, Kayla Betz, Brandi Bratrude, Victor Tkachev, Alex Shalek#, Jose Ordovas-Montanes#, Leslie Kean#