SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology
Summary: Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patie...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222014183 |
| _version_ | 1811264396906725376 |
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| author | Alexsia Richards Max Friesen Andrew Khalil M. Inmaculada Barrasa Lee Gehrke Rudolf Jaenisch |
| author_facet | Alexsia Richards Max Friesen Andrew Khalil M. Inmaculada Barrasa Lee Gehrke Rudolf Jaenisch |
| author_sort | Alexsia Richards |
| collection | DOAJ |
| description | Summary: Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human-induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ, and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages. |
| first_indexed | 2024-04-12T20:02:20Z |
| format | Article |
| id | doaj.art-6fe950a3bccd498c9cd42bb4b1a67f54 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T20:02:20Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6fe950a3bccd498c9cd42bb4b1a67f542022-12-22T03:18:29ZengElsevieriScience2589-00422022-10-012510105146SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathologyAlexsia Richards0Max Friesen1Andrew Khalil2M. Inmaculada Barrasa3Lee Gehrke4Rudolf Jaenisch5Whitehead Institute for Biomedical Research, Cambridge, MA 02127, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02127, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02127, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02127, USADepartment of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02127, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02127, USAWhitehead Institute for Biomedical Research, Cambridge, MA 02127, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02127, USA; Corresponding authorSummary: Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human-induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ, and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages.http://www.sciencedirect.com/science/article/pii/S2589004222014183Health sciencesimmunologyvirologystem cells researchtranscriptomics |
| spellingShingle | Alexsia Richards Max Friesen Andrew Khalil M. Inmaculada Barrasa Lee Gehrke Rudolf Jaenisch SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology iScience Health sciences immunology virology stem cells research transcriptomics |
| title | SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology |
| title_full | SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology |
| title_fullStr | SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology |
| title_full_unstemmed | SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology |
| title_short | SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology |
| title_sort | sars cov 2 infection of human pluripotent stem cell derived liver organoids reveals potential mechanisms of liver pathology |
| topic | Health sciences immunology virology stem cells research transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222014183 |
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