Independent and overlapping transcriptional activation during liver development and regeneration in mice

Authors

  • Nancy Kelley-Loughnane,

    1. Gastroenterology, Hepatology, and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
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  • Gregg E. Sabla,

    1. Gastroenterology, Hepatology, and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
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  • Catherine Ley-Ebert,

    1. Developmental Biology, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
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  • Bruce J. Aronow,

    1. Developmental Biology, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
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  • Jorge A. Bezerra

    Corresponding author
    1. Gastroenterology, Hepatology, and Nutrition, Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati, Cincinnati, OH
    • Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati OH 45229-3039. fax: 513-636-5581.
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Abstract

Liver development and regeneration share the requirement for simultaneous proliferation and acquisition of highly specialized cellular functions. However, little is known about molecules with regulatory roles in both processes. We hypothesized that transcriptional reprogramming induced by regeneration recapitulates that of developing liver. To address this hypothesis, we determined global hepatic gene expression at embryonic day 14.5, postnatal day 14, and 6 to 24 hours following partial hepatectomy using microarrays containing 8,635 cDNAs. Analysis of genes overexpressed during these conditions revealed 3 unique expression patterns. The first was predominantly signature gene clusters specific for each growth phase. Major groups were hematopoiesis-related genes in embryonic livers, metabolic genes during postnatal liver development, and growth/inflammation and metabolic genes during regeneration. The second pattern consisted of dual overexpression during regeneration and at least one phase of development. Consistent with potential regulatory roles in liver growth, most of these transcripts control cell-cell contact, membrane trafficking, cell growth, metabolism, and inflammatory response. The third pattern, revealed by surveying their expression across 76 hepatic and extra-hepatic tissues, uncovered a restricted temporospatial pattern of liver overexpression for CD14, orosomucoid 1, hepcidin, Spi 2.1, Ith3, and Tim-44. In conclusion, these results provide a basis for the identification of gene and gene groups that play critical roles at different phases of liver development and regeneration, and underscore the importance of maintaining metabolic demands during organ growth.

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