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The Hepatic Transcriptome as a Window on Whole-Body Physiology and Pathophysiology

¹ Aventis Inc., Bridgewater, New Jersey 08876, USA
² Aventis Inc., Cambridge, Massachusetts 02139, USA
³ Aventis Inc., Frankfurt, Germany
⁴ Department of Mathematics, University of North Carolina, Chapel Hill, North Carolina, USA
⁵ NIEHS, Research Triangle Park, North Carolina 27709, USA

Correspondence: Address correspondence to: Kevin Morgan, Aventis Inc., U.S. Highway 202/206 North, Bridgewater, NJ 08876, USA; e-mail:Kevin.Morgan{at}aventis.com

Transcriptomics can be a valuable aid to pathologists. The information derived from microarray studies may soon include the entire transcriptomes of most cell types, tissues and organs for the major species used for toxicology and human disease risk assessment. Gene expression changes observed in such studies relate to every aspect of normal physiology and pathophysiology. When interpreting such data, one is forced to look "far from the lamp post," and in so doing, face one’s ignorance of many areas of biology. The central role of the liver in toxicology, as well as in many aspects of whole-body physiology, makes the hepatic transcriptome an excellent place to start your studies. This article provides data that reveals the effects of fasting and circadian rhythm on the rat hepatic transcriptome, both of which need to be kept in mind when interpreting large-scale gene expression in the liver. Once you become comfortable with evaluating mRNA expression profiles and learn to correlate these data with your clinical and morphological observations, you may wonder why you did not start your studies of transcriptomics sooner. Additional study data can be viewed at the journal website at <www.toxpath.org>. Two data files are provided in Excel format, which contain the control animal data from each of the studies referred to in the text, including normalized signal intensity data for each animal (n = 5) in the 6-hour, 24-hour, and 5-day time points. These files are briefly described in the associated ‘Readme’ file, and the complete list of GenBank numbers and Affymetrix IDs are provided in a separate txt file. These files are available at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. Click on the issue link for 33(1), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through <www.toxpath.org>.

Key Words: Liver • rat • fasting • circadian • gene expression • microarray • toxicogenomics • toxicology • rodent • pathology

Abbreviations: mRNA, messenger RNA • CD14, monocyte differentiation antigen CD14 • TNF, Tumor necrosis factor • PCA, principal component analysis • Heat map, Eisen clustering dendogram

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