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Authors: Giobbe et al 

Journal/ Pre-Print:bioRxiv 

Tags: Bioinformatics, Cell Biology, Gut, Stem cells 

Research Highlights 

  1. Gastric organoids were successfully established from pediatric, early fetal and late fetal stomach tissue and expressed previously reported genes representing the stomach at different developmental stages 

  1. Apical-out fetal and pediatric gastric organoids express ACE2 and TMPRSS2, with ACE2 expression being increased in pediatric gastric organoidsWhen infected with SARS-CoV-2live infectious virus was released into the supernatant, the viral replication increasing with the developmental stages  

  1. RNA-seq analysis of SARS-CoV-2 infected gastric organoids shows upregulation of genes involved in viral RNA sensing, inhibition of viral replication and enrichment of genes related to interferon signalling pathways  

Summary 

In this study, gastric organoids were generated from paediatric, early foetal and late foetal stomach tissue. Reversal of organoid polarity allowed infection of gastric organoids with SARS-CoV-2 likely via ACE2 and TMPRSS2 expressed on the apical cell surface. ACE2 expression and viral replication rates were highest in paediatric gastric organoids. Transcriptomic analysis revealed SARS-CoV-2 infection induced upregulation of genes in late foetal and paediatric gastric organoids relating to viral detection and response, the majority of which have been previously identified in SARS-CoV-2 infection. Cells expressing these genes also expressed markers for apoptosis. An enrichment of genes involved in the interferon signalling pathway was also observed.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the virology and/or cell biology of SARS-CoV2/COVID19 

Study Type

  • In silico study / bioinformatics study 

  • In vitro study (ex vivo human gastric organoids) 

  • In vivo study (human stomach biopsies) 

Strengths and limitations of the paper 

Novelty:  

  • Generation of reverse-polarity human fetal and pediatric gastric organoids to allow infection with SARS-CoV-2 from the apical cell surface  

  • SARS-CoV-2 can infect and replicate in fetal and pediatric gastric organoids 

  • Viral replication rates increased with developmental stage  

Standing in the field:SARS-CoV-2 infection in the intestine is well established. DEGs identified in this study were largely in agreement with previously reported upregulated gene expression in SARS-CoV-2 infection. Differential expression of chemokine receptors and ligands has been reported in intestinal organoids but was not observed in this study. 

Appropriate statistics: Yes.  

Viral model used:SARS-CoV2 isolate from a nasopharyngeal swab (14-year-old male patient, Italy) 

Translatability:Currently not 

Main limitations:  

  • Data in Figure 2e hard to interpret as the graphs are small 

  • Figure 3b and c: not entirely clear which groups were compared in DEG analysis 

  • Figure 3f: it would be helpful to see the scale bar for the adjusted p values 

  • High level of variability between organoids (could reflect patient variability though)