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Transcriptome analysis of hepatocytes after partial hepatectomy in rats

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Abstract

After partial hepatectomy (PH), the recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes. Therefore, measuring the transcriptional profiling of hepatocytes after PH will be helpful in exploring the mechanism of liver regeneration (LR). Firstly, hepatocytes were isolated from rat regenerating liver at different time points following PH, and then global gene expression analysis of hepatocytes was performed using Rat Genome 230 2.0 Array. The results demonstrated that 1,417 genes in the array (including 767 known genes) were identified to be LR-related. Clustering analysis demonstrated that 767 known genes fell into six classes with distinct expression kinetics. When gene expression patterns were combined with gene functions, genes involved in acute-phase response and defense response were rapidly elevated in early phases; those in cell proliferation and DNA replication were significantly up-expressed in middle phase; a growing number of cell adhesion-involved genes were up-regulated as regeneration progressed; those in amino acid and lipid metabolism showed persistent down-regulation during LR. Based on the above analyses, it was suggested that hepatocyte defense mechanism was quickly triggered after PH; cell proliferation became active in middle phase; cell adhesion was strengthened in late phase; amino acid and lipid metabolism were attenuated during LR. Additionally, comparative analysis between transcriptional profiling of hepatocytes and regenerating liver indicated a major contribution of hepatocytes to LR.

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Abbreviations

LR:

Liver regeneration

PH:

Partial hepatectomy

H-clustering:

Hierarchical clustering

SO:

Sham operation

RL:

Regenerating liver

GO:

Gene ontology

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Acknowledgment

This work was supported by the National Basic Research 973 Pre-research Program of China (No. 2010CB534905)

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Correspondence to Cunshuan Xu.

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Communicated by: A. Kispert

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Supplementary Table 1

Gene expression profiling data of both sham-operated groups (highlighted in red) and partial-hepatectomized groups (highlighted in blue) for six clusters. *Gray-colored bins represent greater than or equal to threefold up-regulation; spot-marked bins represent greater than or equal to threefold down-regulation; colorless bins represent the insignificant expression. (XLS 403 kb)

Supplementary Table 2

List of the functionally categorized genes enriched in different induction patterns * a Genes enriched in the pattern characterized by “immediate–early and early induction” (clusters 1 and 4). b Genes in the pattern “middle induction” (cluster 2). c Genes in the pattern “middle and late induction” (cluster 3). d Genes in the pattern “persistent repression” (cluster 6). The gray- and spot-marked bins indicate at least threefold up-regulation and at least threefold down-regulation, respectively; and colorless bins represent the insignificant expression. The data presented in bins are the ratio of the signal value of genes in PH groups versus that in control group. (XLS 99 kb)

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Xu, C., Chen, X., Chang, C. et al. Transcriptome analysis of hepatocytes after partial hepatectomy in rats. Dev Genes Evol 220, 263–274 (2010). https://doi.org/10.1007/s00427-010-0345-1

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