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The fetal/neonatal mouse liver exhibits transcriptional features of the adult pancreas.
Citation:
LEE, J. S., W. O. WARD, J. Liu, H. REN, B. VALLANAT, R. GRINDSTAFF, M. H. GEORGE, D. A. DELKER, AND C. CORTON. The fetal/neonatal mouse liver exhibits transcriptional features of the adult pancreas. Presented at Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This work addresses the issues of potentially characterized the gene expression profiles in the livers of young mice and determined there are differences in the expression of xenobiotic metabolizing enzymes compared to young adults that indicate that this population are distinct in their ability to metabolize xenobiotics.
Description:
Metabolic homeostasis of the organism is maintained by the liver’s ability to detoxify and eliminate xenobiotics through the expression of xenobiotic metabolism enxymes (XME). The fetus and neonate have been hypothesized to exhibit increased sensitivity to xenobiotic toxicity. This project was designed to examine differentially expressed genes (DEG) in early life stages in the livers from male C57BL/6 and C3H/HeJ mice. Gene expression profiles were generated using Affymetrix Mouse 430 2.0 arrays for early life stages (GD19, PD7, PD32) and compared to young adults (PD67). Principal component analysis (PCA) showed a clear age-dependent separation in expression profiles between GD19, PD7 and PD67 hepatic transcripts. Differentially expressed genes (DEG) were determined using a one-way ANOVA (p≤0.05) by Rosetta Resolver®, a Benjamini-Hochberg FDR multiple testing correction (<0.05), and a fold-change cutoff of 1.5. Gene expression changes were the most abundant at the early time points in male C57BL/6 (10,068 and 5,989 DEG for GD19 and PD7 respectively). We found 139, 93, and 12 XMEs significantly altered in the GD19, PD7, and PD32 when compared to PD67, respectively. qRT-PCR confirmed altered expression. Because the fetal liver is a site of hematopoiesis, we hypothesized that some of the differences in gene expression between GD19 and PD67 were due to the presence of hematopoietic progenitor cells. We compared the liver profiles with a mouse tissue microarray dataset which included adult tissues involved in hematopoiesis. Suprisingly, PCA and hierarchical clustering showed embryonic liver clustering with embryonic and adult pancreas and separate from adult liver and hematopoietic tissues. These results indicate that there are extensive gene expression differences between early (fetal, neonatal) and adult liver and that the fetal/neonatal liver exhibits transcriptional similarities with the pancreas.