Study: Atlas of Healthy and SHIV-Infected Non-Human Primate Lung and Ileum ACE2+ Cells 8308 cells

Ziegler et al 2020 cellxgene- Ileum cellxgene - Lung

In previously-unpublished NHP (Macaca mulatta) study, lung and ileal tissue was collected following necropsy of healthy adult animals, and analyzed using Seq-Well v1. From lung samples, we recovered at least 17 distinct major cell types, including various lymphoid, myeloid, and stromal populations. ACE2 and TMPRSS2 were primarily expressed in epithelial cells, with 6.7% of type II pneumocytes expressing ACE2, and 3.8% co-expressing ACE2 and TMPRSS2. Notably, the only double positive cells observed were classified within the type II pneumocyte population. We compared ACE2+ with ACE2- type II pneumocytes to explore broader gene programs that differentiate putative SARS-CoV-2-target cells from cells of a similar phenotype and ontogeny (Figure 1D, Supplementary Table 1). Among genes significantly upregulated in ACE2+ type II pneumocytes, we observed IFNGR2 (FDR-adjusted p = 0.022), a receptor for Type II IFN. Notably, previous work has demonstrated limited anti-viral potency of IFNg for SARS-associated coronaviruses, compared to Type I IFN, at least in vitro (Sainz et al., 2004; Zheng et al., 2004). Other co-regulated genes of potential interest include TRIM27 (FDR-adjusted p = 0.025), as well as NT5DC1 (FDR-adjusted p = 0.003) and ARL6IP1 (FDR-adjusted p = 0.047), which were similarly upregulated in A549 adenocarcinoma alveolar basal epithelial cell line following exposure to IFNa and IFNg for 6 hours (Sanda et al., 2006). From ileal samples, we identified ACE2+ cells as absorptive enterocytes, based on specific expression of ACE2 within cells defined by APOA1, SI, FABP6, and ENPEP, among others, by a likelihood-ratio test (p <1E-300, 62% of all absorptive enterocytes). All other epithelial subtypes expressed ACE2 to a lesser extent, and variably co-expressed ACE2 with TMPRSS2.

 

Note that this is a pre-publication dataset, so in this study we include expression of ACE2 and TMPRSS2 across all cells and expression of all genes in the ACE2+ subsets: epithelial cells of the lung and enterocytes in the ileum.

Note that this dataset was generated for a study unrelated to SARS-CoV-2 and no cells in this study were exposed to this virus.

 

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 (listed alphabetically): Shaina L. Carroll, Lucrezia Colonna, Leslie S. Kean, Hans-Peter Kiem, Christopher W. Peterson, Alex K. Shalek, Victor Tkachev, Alison Yu, Hengqui Betty Zheng, Carly G. K. Ziegler