Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift
Abstract Background Liver fibrosis is a wound-healing response to tissue injury and inflammation hallmarked by the extracellular matrix (ECM) protein deposition in the liver parenchyma and tissue remodelling. Different cell types of the liver are known to play distinct roles in liver injury response...
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BMC
2021-12-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-021-08173-1 |
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| author | Maciej Migdał Eugeniusz Tralle Karim Abu Nahia Łukasz Bugajski Katarzyna Zofia Kędzierska Filip Garbicz Katarzyna Piwocka Cecilia Lanny Winata Michał Pawlak |
| author_facet | Maciej Migdał Eugeniusz Tralle Karim Abu Nahia Łukasz Bugajski Katarzyna Zofia Kędzierska Filip Garbicz Katarzyna Piwocka Cecilia Lanny Winata Michał Pawlak |
| author_sort | Maciej Migdał |
| collection | DOAJ |
| description | Abstract Background Liver fibrosis is a wound-healing response to tissue injury and inflammation hallmarked by the extracellular matrix (ECM) protein deposition in the liver parenchyma and tissue remodelling. Different cell types of the liver are known to play distinct roles in liver injury response. Hepatocytes and liver endothelial cells receive molecular signals indicating tissue injury and activate hepatic stellate cells which produce ECM proteins upon their activation. Despite the growing knowledge on the molecular mechanism underlying hepatic fibrosis in general, the cell-type-specific gene regulatory network associated with the initial response to hepatotoxic injury is still poorly characterized. Results In this study, we used thioacetamide (TAA) to induce hepatic injury in adult zebrafish. We isolated three major liver cell types - hepatocytes, endothelial cells and hepatic stellate cells - and identified cell-type-specific chromatin accessibility and transcriptional changes in an early stage of liver injury. We found that TAA induced transcriptional shifts in all three cell types hallmarked by significant alterations in the expression of genes related to fatty acid and carbohydrate metabolism, as well as immune response-associated and vascular-specific genes. Interestingly, liver endothelial cells exhibit the most pronounced response to liver injury at the transcriptome and chromatin level, hallmarked by the loss of their angiogenic phenotype. Conclusion Our results uncovered cell-type-specific transcriptome and epigenome responses to early stage liver injury, which provide valuable insights into understanding the molecular mechanism implicated in the early response of the liver to pro-fibrotic signals. |
| first_indexed | 2024-03-12T17:08:51Z |
| format | Article |
| id | doaj.art-03d34b31747a438db255a3c56987408d |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-12T17:08:51Z |
| publishDate | 2021-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-03d34b31747a438db255a3c56987408d2023-08-06T11:07:45ZengBMCBMC Genomics1471-21642021-12-0122111510.1186/s12864-021-08173-1Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shiftMaciej Migdał0Eugeniusz Tralle1Karim Abu Nahia2Łukasz Bugajski3Katarzyna Zofia Kędzierska4Filip Garbicz5Katarzyna Piwocka6Cecilia Lanny Winata7Michał Pawlak8International Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental GenomicsInternational Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental GenomicsInternational Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental GenomicsNencki Institute of Experimental Biology, Laboratory of CytometryInternational Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental GenomicsDepartment of Experimental Hematology, Institute of Hematology and Transfusion MedicineNencki Institute of Experimental Biology, Laboratory of CytometryInternational Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental GenomicsInternational Institute of Molecular and Cell Biology in Warsaw, Laboratory of Zebrafish Developmental GenomicsAbstract Background Liver fibrosis is a wound-healing response to tissue injury and inflammation hallmarked by the extracellular matrix (ECM) protein deposition in the liver parenchyma and tissue remodelling. Different cell types of the liver are known to play distinct roles in liver injury response. Hepatocytes and liver endothelial cells receive molecular signals indicating tissue injury and activate hepatic stellate cells which produce ECM proteins upon their activation. Despite the growing knowledge on the molecular mechanism underlying hepatic fibrosis in general, the cell-type-specific gene regulatory network associated with the initial response to hepatotoxic injury is still poorly characterized. Results In this study, we used thioacetamide (TAA) to induce hepatic injury in adult zebrafish. We isolated three major liver cell types - hepatocytes, endothelial cells and hepatic stellate cells - and identified cell-type-specific chromatin accessibility and transcriptional changes in an early stage of liver injury. We found that TAA induced transcriptional shifts in all three cell types hallmarked by significant alterations in the expression of genes related to fatty acid and carbohydrate metabolism, as well as immune response-associated and vascular-specific genes. Interestingly, liver endothelial cells exhibit the most pronounced response to liver injury at the transcriptome and chromatin level, hallmarked by the loss of their angiogenic phenotype. Conclusion Our results uncovered cell-type-specific transcriptome and epigenome responses to early stage liver injury, which provide valuable insights into understanding the molecular mechanism implicated in the early response of the liver to pro-fibrotic signals.https://doi.org/10.1186/s12864-021-08173-1LiverHepatocytesStellate cellsEndothelial cellsChromatinTranscriptomics |
| spellingShingle | Maciej Migdał Eugeniusz Tralle Karim Abu Nahia Łukasz Bugajski Katarzyna Zofia Kędzierska Filip Garbicz Katarzyna Piwocka Cecilia Lanny Winata Michał Pawlak Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift BMC Genomics Liver Hepatocytes Stellate cells Endothelial cells Chromatin Transcriptomics |
| title | Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift |
| title_full | Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift |
| title_fullStr | Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift |
| title_full_unstemmed | Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift |
| title_short | Multi-omics analyses of early liver injury reveals cell-type-specific transcriptional and epigenomic shift |
| title_sort | multi omics analyses of early liver injury reveals cell type specific transcriptional and epigenomic shift |
| topic | Liver Hepatocytes Stellate cells Endothelial cells Chromatin Transcriptomics |
| url | https://doi.org/10.1186/s12864-021-08173-1 |
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