title: Transcriptional ontogeny of the developing liver.
abstract: BACKGROUND
  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 was carried out.
  
  
  RESULTS
  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 32) compared to that in the adult liver (PND67) using full-genome microarrays. 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 under expressed. Comparison of the dataset 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) under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes.
  
  
  CONCLUSIONS
  Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.
authors.affiliation: National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA. lee.janices@epa.gov
authors.forename: Janice S
authors.initials: JS
authors.lastname: Lee
authors.forename: William O
authors.initials: WO
authors.lastname: Ward
authors.forename: Geremy
authors.initials: G
authors.lastname: Knapp
authors.forename: Hongzu
authors.initials: H
authors.lastname: Ren
authors.forename: Beena
authors.initials: B
authors.lastname: Vallanat
authors.forename: Barbara
authors.initials: B
authors.lastname: Abbott
authors.forename: Karen
authors.initials: K
authors.lastname: Ho
authors.forename: Seth J
authors.initials: SJ
authors.lastname: Karp
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Corton
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D041905:Erythroid Cells / Q000378:metabolism; D005260:Female; D005333:Fetus; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000254:growth & development* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D010179:Pancreas / Q000254:growth & development / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein / Q000235:genetics; D011247:Pregnancy; D012261:Ribonucleoproteins / Q000235:genetics; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D015262:Xenobiotics / Q000378:metabolism
chemical_list: C410808:Makorin ring finger protein 1; D009419:Nerve Tissue Proteins; D012261:Ribonucleoproteins; D015262:Xenobiotics; D038941:Polypyrimidine Tract-Binding Protein