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. / Ægidius, Helene M.; Veidal, Sanne S.; Feigh, Michael; Hallenborg, Philip; Puglia, Michele; Pers, Tune H.; Vrang, Niels; Jelsing, Jacob; Kornum, Birgitte R.; Blagoev, Blagoy; Rigbolt, Kristoffer T.G.
In: Scientific Reports, Vol. 10, No. 1, 1148, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis
AU - Ægidius, Helene M.
AU - Veidal, Sanne S.
AU - Feigh, Michael
AU - Hallenborg, Philip
AU - Puglia, Michele
AU - Pers, Tune H.
AU - Vrang, Niels
AU - Jelsing, Jacob
AU - Kornum, Birgitte R.
AU - Blagoev, Blagoy
AU - Rigbolt, Kristoffer T.G.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-020-58059-7
DO - 10.1038/s41598-020-58059-7
M3 - Journal article
C2 - 31980690
AN - SCOPUS:85078279199
VL - 10
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 1148
ER -
ID: 236509939