Gene Expression in Perivenous Hepatocytes: A Laser Capture Microdissection and Transcriptomic Analysis.
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ABSTRACT: Differential expression of genes and proteins, as well as physiological processes, along the hepatic acinus, known collectively as hepatic zonation, is a fundamental feature of hepatic physiology. However, the precise cellular location of only a relatively small proportion of the ~14,000 genes expressed in the liver is known. This is critical information for understanding hepatic physiology as well as for the accurate targeting of gene transfer vectors for gene therapy. We have employed laser capture microdissection (LCM) and unbiased transcriptomic analysis of the normal adult mouse liver to define gene expression in a very distinct population of cells in the acinus, the glutamine-synthetase sub-compartment of perivenous hepatocytes, encompassing a one- to two-layer of cells surrounding the centrilobular vein. We confirmed the location of a number of genes whose expression is known to be restricted to these cells by virtue of immunohistochemistry or in situ hybridization (Slc1a2, Glul, Rhbg). We also identified genes whose expression had not previously been reported to be enriched in these cells (e.g. Sp5, Vldlr, Lpl, Gabrb3, Rcan2). Transcription factor analysis of the differentially expressed genes suggested important roles, in these cells, for members of the polycomb group, Wt1 and Tbx3. Collectively, our findings highlight the utility of combined LCM and transcriptome analysis for the identification of novel functions of distinct subclasses of hepatocytes. We plan to extend this approach to the mapping of physiological function across hepatic acini of the human liver. Comparison of mRNA expression by two hepatic cell populations: the glutamine synthetase-subcompartment of the perivenous compartment and zones 1+2 of the hepatic acinus Cells were isolated by laser capture microdissection and mRNA extracted by standard protocol.
ORGANISM(S): Mus musculus
SUBMITTER: John Brosnan
PROVIDER: E-GEOD-48273 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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