Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse liver regeneration after partial hepatectomy

ABSTRACT: The goal of this study is to obtain an expression profile of regenerating mouse livers. We used microarray analysis to study the gene groups coordinately expressed temporally during mouse a liver regeneration. One of the syn-expression groups that showed a sharp rise in gene expression immediately after hepatectomy contains a set pancreatic exocrine genes. The syn-expression profile of pancreatic genes and the pancreatic-specific transcription factors Ptf1a and Ipf1 was confirmed using real-time PCR. Electron microscopic examination showed the presence of morphological features reminiscent of pancreatic acinar cells with the presence of characteristic zymogen granules and ER organization. These results indicate that there is a transient liver-to-pancreas transdifferentiation event at the beginning of liver regeneration. A strong coordinated up-regulation of pancreatic genes was found to accompany the injury response in the pancreas, suggesting a compensatory mechanism for pancreatic functions. There seems to be a relationship between the induction of pancreatic genes and acute phase response at the beginning of liver regeneration. Experiment Overall Design: Total RNA was extracted from livers of mice recovered at Experiment Overall Design: various hours after partial hepatectomy (PHx 4h, 8h, 12h, 36h, Experiment Overall Design: 48h, 72h). We grouped livers of four to six mice together for Experiment Overall Design: RNA extraction. Genes showed differentially up- or downregulated Experiment Overall Design: by two-fold with respect to the normal mouse livers Experiment Overall Design: were identified using GeneSpring software version 7.2 (Silicon Experiment Overall Design: Genetics, Agilent Technologies).

ORGANISM(S): Mus musculus

SUBMITTER: Ann-Ping Tsou

PROVIDER: E-GEOD-4528 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Normal adult liver is uniquely capable of renewal; and repair after injury. Whether this response; represents simple hyperplasia of various liver elements; or requires recapitulation of the genetic program of; the developing liver is not known. To study these possibilities, we examined transcriptional programs of adult liver after partial hepatectomy and contrasted these with developing embryonic liver. Principal component analysis demonstrated that the time series of gene expression during liver regeneration does not segregate according to developmental transcription patterns. Gene ontology analysis revealed that liver restoration after hepatectomy and liver development differ dramatically with regard to transcription factors and chromatin structure modification. In contrast, the tissues are similar with regard to proliferationassociated genes. Consistent with these findings, realtime polymerase chain reaction showed transcription factors known to be important in liver development are not induced during liver regeneration. These three lines of evidence suggest that at a transcriptional level, restoration of liver mass after injury is best described as hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern of gene expression may underlie the unique capacity of the liver to repair itself after injury. Experiment Overall Design: In order to elucidate the molecular similarities between regenerating and developing liver, we performed high-density microarray analysis using Affymetrix MG 430 2.0 chips for targets at 0, 1, 2, 6, 12, 18, 24, 30, 48, and 72 hours after partial hepatectomy and at 10.5, 11.5, 12.5, 13.5, 14.5, and 16.5 days post conception (dpc). Experiment Overall Design: Each experimental time point is represented by two separate samples, each consisting of at least 3 pooled tissues from different animals. For example, 6 hepatectomies were performed for the 1 hour post-hepatectomy time point. Time 0 is used as control.

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Transcription profiling of mouse liver regeneration after partial hepatectomy

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