Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis

Autor:	Niels Vrang, Michele Puglia, Tune H. Pers, Birgitte Rahbek Kornum, Michael Feigh, Helene M Ægidius, Jacob Jelsing, Philip Hallenborg, Sanne Skovgård Veidal, Blagoy Blagoev, Kristoffer T.G. Rigbolt
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Male Proteomics 0301 basic medicine Physiology Quantitative proteomics Metabolic disorders lcsh:Medicine Pathogenesis Computational biology Biology Diet High-Fat Article Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Single-cell analysis Non-alcoholic Fatty Liver Disease Tandem Mass Spectrometry medicine Animals Obesity lcsh:Science Multidisciplinary Hepatology Drug discovery Sequence Analysis RNA lcsh:R Endocrine system and metabolic diseases Lipid metabolism medicine.disease Phenotype Computational biology and bioinformatics Mice Inbred C57BL Disease Models Animal 030104 developmental biology Liver RNA 030211 gastroenterology & hepatology lcsh:Q Single-Cell Analysis Steatohepatitis Systems biology Sequence Alignment Diet-induced obese Chromatography Liquid
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Ægidius, H M, Veidal, S S, Feigh, M, Hallenborg, P, Puglia, M, Pers, T H, Vrang, N, Jelsing, J, Kornum, B R, Blagoev, B & Rigbolt, K T G 2020, ' Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis ', Scientific Reports, vol. 10, no. 1, 1148 . https://doi.org/10.1038/s41598-020-58059-7 Scientific Reports
ISSN:	2045-2322
DOI:	10.1038/s41598-020-58059-7
Popis:	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.
Databáze:	OpenAIRE
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