Project description:This SuperSeries is composed of the following subset Series: GSE20425: Hepatic gene expression during liver regeneration in response to partial hepatectomy: early time points (0.5h,1h,2h,4h) GSE20426: Hepatic gene expression during liver regeneration in response to partial hepatectomy: late time points (24h, 38h, 48h) Refer to individual Series
Project description:Bile acid return from the intestine and attendant signaling is necessary for liver regeneration after partial hepatectomy or CCl4 injury Three groups of rat liver were examined at 4 time points (0, 4h, 12h, 24h) after partial hepatectomy; RNA from whole rat liver was isolated and deep sequencing was performed using the Illumina TruSeq platform
Project description:The process of liver regeneration can be divided into a series of stages that include initial inductive or priming events through cellular mitosis. Following two-thirds liver resection, the liver undergoes the “priming” phase, in which cytokines TNF-a and IL-6 activate their respective receptors in hepatocytes. This leads to the activation of several key transcription factors: NF-kB, AP-1, Stat 3, Stat 1, and C/EBP-b and -d . These transcription factors induce the expression of immediate early genes. HGF is also expressed at this time and involved in the transition of quiescent hepatocytes into the G1 phase of the cell cycle. During the G1 phase, delayed early genes are expressed followed by induction of cell cycle–related genes, both of which require new protein synthesis for their production. Increased expression of FoxM1B and TGF-a occurs at the G1/S transition and is correlated with increased expression of cyclinD1 and decreased expression of cdk inhibitors. During the G2/M phase of the cell cycle, FoxM1B directly elevates cyclinB1, cyclinB2, and cdc25B expression. Additionally, FoxM1B is associated with increased cyclinF and p55cdc, which are involved in completion of the cell cycle following partial hepatectomy. In mice, two-thirds partial hepatectomy promotes proliferation of liver cells and rapid growth of the remaining liver tissue, resulting in complete restoration of organ mass in approximately 7 days (Mackey S. et al. Hepatology 2003 Dec;38(6):1349-52). Liver tissue was collected 0h, 24h, 38h, and 48h after partial hepatectomy or sham surgery from both young (5-6 months) and old (25-27 months) CB6F1 mice. All control and partial hepatectomy samples were assayed in triplicate. Relative gene expression levels were determined using Affymetrix moe430_2 oligo arrays.
Project description:The recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes after partial hepatectomy. Studying the gene expression profiles of hepatocytes after partial hepatectomy will be helpful in exploring the mechanism of liver regeneration. We used microarrays to further highlight the regulatory role of hepatocyte in liver regeneration at gene transcription level. Rat liver regeneration after partial hepatectomy (PH) is a good model to study the regulation of cell proliferation. We isolated hepatocytes from regenerating liver at 9 time points (2, 6, 12,24, 30, 36, 72, 120, and 168h) after PH and measured gene expression profiles of hepatocytes from 2h to 168h with rat Genome 230 2.0 gene chip. Each sample corresponding to one time point was hybridized onto one array. The experiment was repeated 3 times for each time point. In total, 10 time points were measured and 0h was used control group. After careful quality control analyses of each chip, Affymetrix GCOS 2.0 software was used to analyze the data. The relevance of gene expression profiles and biological processes was analyzed by bioinformatics and systems biology.
Project description:Deletion of the RPS6 gene in mouse liver results in the inhibition of 40S ribosome biogenesis and the failure of hepatocytes to enter S-phase following partial hepatectomy. This microarray experiment was designed to assess the effects of RPS6 deletion on the expression of genes involved in liver regeneration following partial hepatectomy. Keywords: time course, liver RNA was isolated from mouse livers at different time-points following partial hepatectomy. Conditional deletion of the RPS6 gene was perfomed by injecting polyinosinic-polycytidylic acid in mice harbouring a floxed version of the RPS6 gene and a cre recombinase under the regulation of an interferon responsive promoter (MX-CRE). The mice used a control have also a floxed version of the RPS6 gene but lack the cre recombinaste transgene.
Project description:Liver regeneration has important implications because many therapeutic strategies for the surgical treatment of liver diseases, such as removal of liver tumors and liver transplantation, depend on the ability of the liver to regenerate physically and functionally. Recent studies reported that lncRNAs control cell proliferation in hepatocellular carcinoma (HCC). However, the role of lncRNAs in liver regeneration and the overall mechanisms remain largely unknown. To address this issue, we carried out a genome-wide lncRNA microarray analysis during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various time points. The results revealed differential expression of thousands of lncRNAs during liver regeneration. Six-week-old male wildtype C57Bl/6 mouse liver samples were obtained at 0, 1.5, 12, and 24 hours after 2/3 PH, and three mice were analyzed for each time point. Total RNA was isolated using Trizol.Mouse Stringent LncRNA Array (4 x 44K, ArrayStar, Rockville, MD) were used to monitor the expression level of approximately 14000 lncRNAs identified from the NCBI RefSeq, UCSC, RNAdb2.0, NRED, Fantom3.0 and UCRs. LncRNAs differentially expressed were identified by comparing expression levels during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various time points.
Project description:Purpose: The goal of this study was to determine biological consequences during liver regeneration following partial hepatectomy in mice by next-generation sequencing. A particular interest was to compare mice with either a floxed b-PDGFR allele to mice that harbored a deletion of b-PDGFR in hepatic stellate cells (HSCs), by crossing b-PDGFR fl/fl mice with transgenic GFAP-Cre mice. Methods: b-PDGFR fl/fl mice or mice with a HSC-specific deletion of b-PDGFR underwent either sham operation or 70% partial hepatectomy. Following 72 hours, livers were collected and total RNA was extracted using tizol, followed by a purification using Quiagen spin columns including an on-column DNAse digestion step. Conclusion: Our study represents a detailed analysis of hepatic transcriptome, with biologic replicates, generated by RNA-seq technology of livers following sham operation or partial hepatectomy in b-PDGFR fl/fl mice or b-PDGFRfl/fl/GRAP-Cre mice. Whole liver mRNA profiles of sham operated livers or livers collected 72hours after partial hepatectomy of beta-PDGFR fl/fl and beta-PDGFR fl/fl/GFAP-Cre (creating a hepatic stellate cell-specific deletion of b-PDGFR) mice were generated by deep sequencing, in duplicate, using Illumina HiSeq2000.
Project description:Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. Loss or reduction of KLF6 is linked with progression of experimental and human hepatocellular carcinoma. Despite its important contributions to liver homeostasis and growth, there are no data characterizing the involvement of KLF6 to hepatic regeneration. Microarray data from wildtype and DeltaKlf6 mice were used to identify regulating mechanisms and potential mediators within liver regeneration Wildtype and hepatocyte specific Klf6 knockout mice (DeltaKlf6) were employed for 70% partial liver resection/hepatectomy (PHx) in order to analyse liver regeneration. Twelve hours after partial hepatectomy animals were scrificed and remnant liver tissue was used for further experiemnts. For the overall study we used 6 animals per group, and included RNA from liver tissue of 3 wildtype and 3 DeltaKlf6 animals for the microarray analysis. Wildtype animals were used as controls.
Project description:The study examined the role of TNF alpha in regulation of liver regeneration. For this purpose animals were divided in three groups of healthy controls, 2/3 partial hepatectomy alone, and animals pretreated with TNF alpha antagonist followed by 2/3 partial hepatectomy. Liver regeneration responses were then examined in conjunction with gene expression analysis at the peak of partial hepatectomy induced DNA synthesis. Substantive differences were identified in multiple gene ontology groups and cellular events and processes to indicate that TNF alpha was deleterious for partial hepatectomy induced liver regeneration.