Project description:Sex differences in liver gene expression are dictated by sex-differences in circulating growth hormone (GH) profiles. Presently, the pituitary hormone dependence of mouse liver gene expression was investigated on a global scale to discover sex-specific early GH response genes that might contribute to sex-specific regulation of downstream GH targets and to ascertain whether intrinsic sex-differences characterize hepatic responses to plasma GH stimulation. RNA expression analysis using 41,000-feature microarrays revealed two distinct classes of sex-specific mouse liver genes: genes subject to positive regulation (class-I) and genes subject to negative regulation by pituitary hormones (class-II). Genes activated or repressed in hypophysectomized (Hypox) mouse liver within 30-90min of GH pulse treatment at a physiological dose were identified as direct targets of GH action (early response genes). Intrinsic sex-differences in the GH responsiveness of a subset of these early response genes were observed. Notably, 45 male-specific genes, including five encoding transcriptional regulators that may mediate downstream sex-specific transcriptional responses, were rapidly induced by GH (within 30min) in Hypox male but not Hypox female mouse liver. The early GH response genes were enriched in 29 male-specific targets of the transcription factor Mef2, whose activation in hepatic stellate cells is associated with liver fibrosis leading to hepatocellular carcinoma, a male-predominant disease. Thus, the rapid activation by GH pulses of certain sex-specific genes is modulated by intrinsic sex-specific factors, which may be associated with prior hormone exposure (epigenetic mechanisms) or genetic factors that are pituitary-independent, and could contribute to sex-differences in predisposition to liver cancer or other hepatic pathophysiologies.
Project description:Gene expression in adult male and female mouse liver was analyzed based on nuclear RNA-seq, as part of a study on hepatic lincRNAs.
Project description:Through deep RNA-seq in human subcutaneous adipose bioposies and established long noncoding RNAs (lincRNAs) annotations, we identified human lincRNAs expressed in all subjects, including subsets of lincRNAs that exhibit differential expression by sex and race. Our comprehensive profiling on subcutaneous adipose lincRNA transcriptome provides great resource to advance novel understanding of genetic regulation in adipose biology.
Project description:Gene expression in male mouse liver was assayed by RNA-seq, as part of a study to study cellular compartmentalization of hepatic lincRNAs.
Project description:Gene expression in intact and hypophysectomized adult mouse liver was assayed by RNA-seq analysis of total liver RNA, as part of a study of growth hormone regulation of hepatic lincRNAs.
