Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis
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- Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis
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To improve the understanding of the complex biological processes underlying the development of non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell RNA-sequencing was used to characterize tissue biopsies from histologically validated diet-induced obese (DIO) NASH mice compared to chow-fed controls. Bulk RNA-sequencing and proteomics showed a clear distinction between phenotypes and a good correspondence between mRNA and protein level regulations, apart from specific regulatory events discovered by each technology. Transcriptomics-based gene set enrichment analysis revealed changes associated with key clinical manifestations of NASH, including impaired lipid metabolism, increased extracellular matrix formation/remodeling and pro-inflammatory responses, whereas proteomics-based gene set enrichment analysis pinpointed metabolic pathway perturbations. Integration with single-cell RNA-sequencing data identified key regulated cell types involved in development of NASH demonstrating the cellular heterogeneity and complexity of NASH pathogenesis.
Original language | English |
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Article number | 1148 |
Journal | Scientific Reports |
Volume | 10 |
Issue number | 1 |
Number of pages | 12 |
ISSN | 2045-2322 |
DOIs | |
Publication status | Published - 2020 |
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