Initiation of hepatic stellate cell activation extends into chronic liver disease
Abstract Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. H...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2021-11-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04377-1 |
| _version_ | 1818743730287411200 |
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| author | Vincent De Smet Nathalie Eysackers Vincent Merens Mina Kazemzadeh Dastjerd Georg Halder Stefaan Verhulst Inge Mannaerts Leo A. van Grunsven |
| author_facet | Vincent De Smet Nathalie Eysackers Vincent Merens Mina Kazemzadeh Dastjerd Georg Halder Stefaan Verhulst Inge Mannaerts Leo A. van Grunsven |
| author_sort | Vincent De Smet |
| collection | DOAJ |
| description | Abstract Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease. |
| first_indexed | 2024-12-18T02:33:03Z |
| format | Article |
| id | doaj.art-8ea65b2a9036464990e291a1c81feff9 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-18T02:33:03Z |
| publishDate | 2021-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-8ea65b2a9036464990e291a1c81feff92022-12-21T21:23:51ZengNature Publishing GroupCell Death and Disease2041-48892021-11-01121211010.1038/s41419-021-04377-1Initiation of hepatic stellate cell activation extends into chronic liver diseaseVincent De Smet0Nathalie Eysackers1Vincent Merens2Mina Kazemzadeh Dastjerd3Georg Halder4Stefaan Verhulst5Inge Mannaerts6Leo A. van Grunsven7Vrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupVrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupVrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupVrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupKU Leuven, VIB Center for Cancer BiologyVrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupVrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupVrije Universiteit Brussel (VUB), Liver Cell Biology Research GroupAbstract Activated hepatic stellate cells (aHSC) are the main source of extra cellular matrix in liver fibrosis. Activation is classically divided in two phases: initiation and perpetuation. Currently, HSC-based therapeutic candidates largely focus on targeting the aHSCs in the perpetuation phase. However, the importance of HSC initiation during chronic liver disease (CLD) remains unclear. Here, we identified transcriptional programs of initiating and activated HSCs by RNA sequencing, using in vitro and in vivo mouse models of fibrosis. Importantly, we show that both programs are active in HSCs during murine and human CLD. In human cirrhotic livers, scar associated mesenchymal cells employ both transcriptional programs at the single cell level. Our results indicate that the transcriptional programs that drive the initiation of HSCs are still active in humans suffering from CLD. We conclude that molecules involved in the initiation of HSC activation, or in the maintenance of aHSCs can be considered equally important in the search for druggable targets of chronic liver disease.https://doi.org/10.1038/s41419-021-04377-1 |
| spellingShingle | Vincent De Smet Nathalie Eysackers Vincent Merens Mina Kazemzadeh Dastjerd Georg Halder Stefaan Verhulst Inge Mannaerts Leo A. van Grunsven Initiation of hepatic stellate cell activation extends into chronic liver disease Cell Death and Disease |
| title | Initiation of hepatic stellate cell activation extends into chronic liver disease |
| title_full | Initiation of hepatic stellate cell activation extends into chronic liver disease |
| title_fullStr | Initiation of hepatic stellate cell activation extends into chronic liver disease |
| title_full_unstemmed | Initiation of hepatic stellate cell activation extends into chronic liver disease |
| title_short | Initiation of hepatic stellate cell activation extends into chronic liver disease |
| title_sort | initiation of hepatic stellate cell activation extends into chronic liver disease |
| url | https://doi.org/10.1038/s41419-021-04377-1 |
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