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Transcriptional Ontogeny of the Developing Liver
LEE, J. S., W. O. WARD, G. W. KNAPP, H. Ren, B. VALLANAT, B. D. ABBOTT, K. Ho, S. J. Karp, AND C. CORTON. Transcriptional Ontogeny of the Developing Liver. BMC Genomics. BioMed Central Ltd, London, Uk, 13(1):33, (2012).
During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hematopoietic stem cells, the source for a number of blood cells including nucleated erythrocytes. A comprehensive analysis of the transcriptional changes that occur during the early stages of development to adulthood in the liver has not been carried out. We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the data set to a number of previously published microarray datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with hematopoietic cells and growth in hepatocytes. These findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical exposure as a function of early life-stages.
These findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical exposure as a function of early life-stages.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH