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

Helene M Ægidius, Sanne S Veidal, Michael Feigh, Philip Hallenborg, Michele Puglia, Tune H Pers, Niels Vrang, Jacob Jelsing, Birgitte R Kornum, Blagoy Blagoev, Kristoffer T G Rigbolt

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Abstrakt

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.

OriginalsprogEngelsk
Artikelnummer1148
TidsskriftScientific Reports
Vol/bind10
Udgave nummer1
Antal sider12
ISSN2045-2322
DOI
StatusUdgivet - 2020

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