Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection
Abstract Human intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a framework combining single‐cell RNA‐Seq and h...
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Online Access: | https://doi.org/10.15252/msb.20209833 |
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doaj-bc9365d62fcc43ee971282a376a93b512021-07-29T07:30:28ZengWileyMolecular Systems Biology1744-42922021-07-01177n/an/a10.15252/msb.20209833Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infectionSergio Triana0Megan L Stanifer1Camila Metz‐Zumaran2Mohammed Shahraz3Markus Mukenhirn4Carmon Kee5Clara Serger6Ronald Koschny7Diana Ordoñez‐Rueda8Malte Paulsen9Vladimir Benes10Steeve Boulant11Theodore Alexandrov12Structural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg GermanyDepartment of Infectious Diseases, Molecular Virology Heidelberg University Heidelberg GermanyDepartment of Infectious Diseases, Virology Heidelberg University Heidelberg GermanyStructural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg GermanyDepartment of Infectious Diseases, Virology Heidelberg University Heidelberg GermanyResearch Group “Cellular Polarity and Viral Infection” German Cancer Research Center (DKFZ) Heidelberg GermanyStructural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg GermanyDepartment of Internal Medicine IV Interdisciplinary Endoscopy Center University Hospital Heidelberg Heidelberg GermanyFlow Cytometry Core Facility European Molecular Biology Laboratory Heidelberg GermanyFlow Cytometry Core Facility European Molecular Biology Laboratory Heidelberg GermanyGenomics Core Facility European Molecular Biology Laboratory Heidelberg GermanyResearch Group “Cellular Polarity and Viral Infection” German Cancer Research Center (DKFZ) Heidelberg GermanyStructural and Computational Biology Unit European Molecular Biology Laboratory Heidelberg GermanyAbstract Human intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a framework combining single‐cell RNA‐Seq and highly multiplex RNA FISH and applied it to human intestinal organoids infected with human astrovirus, a model human enteric virus. We found that interferon controls the infection and that astrovirus infects all major cell types and lineages and induces expression of the cell proliferation marker MKI67. Intriguingly, each intestinal epithelial cell lineage exhibits a unique basal expression of interferon‐stimulated genes and, upon astrovirus infection, undergoes an antiviral transcriptional reprogramming by upregulating distinct sets of interferon‐stimulated genes. These findings suggest that in the human intestinal epithelium, each cell lineage plays a unique role in resolving virus infection. Our framework is applicable to other organoids and viruses, opening new avenues to unravel roles of individual cell types in viral pathogenesis.https://doi.org/10.15252/msb.20209833astrovirusimmune responseintestinal epithelial cellsorganoidssingle‐cell transcriptomics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sergio Triana Megan L Stanifer Camila Metz‐Zumaran Mohammed Shahraz Markus Mukenhirn Carmon Kee Clara Serger Ronald Koschny Diana Ordoñez‐Rueda Malte Paulsen Vladimir Benes Steeve Boulant Theodore Alexandrov |
spellingShingle |
Sergio Triana Megan L Stanifer Camila Metz‐Zumaran Mohammed Shahraz Markus Mukenhirn Carmon Kee Clara Serger Ronald Koschny Diana Ordoñez‐Rueda Malte Paulsen Vladimir Benes Steeve Boulant Theodore Alexandrov Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection Molecular Systems Biology astrovirus immune response intestinal epithelial cells organoids single‐cell transcriptomics |
author_facet |
Sergio Triana Megan L Stanifer Camila Metz‐Zumaran Mohammed Shahraz Markus Mukenhirn Carmon Kee Clara Serger Ronald Koschny Diana Ordoñez‐Rueda Malte Paulsen Vladimir Benes Steeve Boulant Theodore Alexandrov |
author_sort |
Sergio Triana |
title |
Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection |
title_short |
Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection |
title_full |
Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection |
title_fullStr |
Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection |
title_full_unstemmed |
Single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection |
title_sort |
single‐cell transcriptomics reveals immune response of intestinal cell types to viral infection |
publisher |
Wiley |
series |
Molecular Systems Biology |
issn |
1744-4292 |
publishDate |
2021-07-01 |
description |
Abstract Human intestinal epithelial cells form a primary barrier protecting us from pathogens, yet only limited knowledge is available about individual contribution of each cell type to mounting an immune response against infection. Here, we developed a framework combining single‐cell RNA‐Seq and highly multiplex RNA FISH and applied it to human intestinal organoids infected with human astrovirus, a model human enteric virus. We found that interferon controls the infection and that astrovirus infects all major cell types and lineages and induces expression of the cell proliferation marker MKI67. Intriguingly, each intestinal epithelial cell lineage exhibits a unique basal expression of interferon‐stimulated genes and, upon astrovirus infection, undergoes an antiviral transcriptional reprogramming by upregulating distinct sets of interferon‐stimulated genes. These findings suggest that in the human intestinal epithelium, each cell lineage plays a unique role in resolving virus infection. Our framework is applicable to other organoids and viruses, opening new avenues to unravel roles of individual cell types in viral pathogenesis. |
topic |
astrovirus immune response intestinal epithelial cells organoids single‐cell transcriptomics |
url |
https://doi.org/10.15252/msb.20209833 |
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