Single nucleus RNA-seq gene expression profiling for protein coding and lncRNA genes using livers of male and female mice, with GH infusion, and following TCPOBOP exposure
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ABSTRACT: Single nucleus RNA-seq gene expression profiling was carried out for protein coding and lncRNA genes using nuclei extracted from livers from adult male and female mice; from male mice infused with GH continuously for one week, mimicking the female plasma GH pattern; and from male and female mice exposed to TCPOBOP, a xenobiotic agonist ligand of the nuclear receptor CAR, which perturbs sex-biased gene expression in the liver. Our analysis of these rich single nucleus, mouse liver transcriptomic datasets, comprised of 32,000 liver nuclei representing 9 major liver cell types, revealed: 1) the expression of sex-biased genes and their key GH-dependent transcriptional regulators is primarily restricted to hepatocytes and is largely not a feature of liver non-parenchymal cells; 2) many sex-biased transcripts show sex-dependent zonation within the liver lobule; 3) gene expression is substantially feminized in both periportal and pericentral hepatocytes when male mice are infused with GH continuously; 4) sequencing nuclei increases the sensitivity for detecting thousands of nuclear-enriched long-noncoding RNAs (lncRNAs) and enables determination of their liver cell type-specificity, sex-bias and hepatocyte zonation profiles; 5) the periportal to pericentral hepatocyte cell ratio is significantly higher in male than female liver; and 6) TCPOBOP exposure disrupts both sex-specific gene expression and hepatocyte zonation within the liver lobule. These findings highlight the complex interconnections between hepatic sexual dimorphism and zonation at the single-cell level and reveal how endogenous hormones and foreign chemical exposure can alter these interactions across the liver lobule with large effects on both protein-coding genes and lncRNAs.
ORGANISM(S): Mus musculus
PROVIDER: GSE188488 | GEO | 2022/04/25
REPOSITORIES: GEO
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