Project description:Transcriptional profiling of PNPase KO liver hepatocytes (HepKO) generated from Albumin-Cre/wt (liver-specific) Pnpt1 fl/fl C57BL/6J mice. Samples comparing liver hepatocyte PNPase KO (HepKO) cells to litter-, age-, and sex-matched wildtype hepatocyte control cells. The goal of this experiment was to determine effects of PNPase loss on the total RNA transcriptome under physiologic in vivo conditions.
Project description:Liver transcriptome profiling of liver specific miR-122 knockout (miR-122loxP/loxP Alb-Cre) and control (miR-122loxP/loxP) male mice. Expression profile of several hundred mRNAs that include miR-122 targets were altered in miR-122 KO livers. Loss of miR-122 in the germ line resulted in significant changes in hepatic gene expression profile. Among the upregulated genes many are direct targets of miR-122 GSM517838-GSM517847: Liver transcriptome profiling of liver specific miR-122 knockout and control male mice. Total liver RNA from 8 week old five control and five liver-specific miR-122 knock out male mice (C57/BL6J background) GSM791601-GSM791604: Liver transcriptome profiling of germ-line miR-122 knockout and control male mice. Liver RNA from 5 week old control (floxed) and miR-122KO mice were analyzed by mouse whole transcriptome profiling.
Project description:Transcriptional profiling of muscle and liver samples from muscle- and liver-specific AIF knockout mice respectively. Samples obtained from 8 week old, male knockouts, backcrossed 8 times onto the C57Bl6 background are compared to those obtained from littermate control mice. Keywords: disease state analysis, AIF knockout, metabolism
Project description:Transcriptional profiling of muscle and liver samples from muscle- and liver-specific AIF knockout mice respectively. Samples obtained from 8 week old, male knockouts, backcrossed 8 times onto the C57Bl6 background are compared to those obtained from littermate control mice. Keywords: disease state analysis, AIF knockout, metabolism
Project description:Genome wide DNA methylation profiling of liver tissues from 17 months old male mice belonging to either the C57BL/6J, the CD1 or the Sv129Ev strain and exposed to LCPS. The Illumina Infinium Mouse Methylation Beadchip was used to obtain DNA methylation profiles across approximately 285,000 CpGs in liver samples. Samples included 19 C57Bl/6J mice, 12 CD1 mice, and 16 Sv129Ev mice.
Project description:The liver has a remarkable capacity to regenerate and thus compensates for repeated injuries through toxic chemicals, drugs, alcohol, or malnutrition for decades. However, largely unknown is how and when alterations in the liver occur due to tolerable damaging insults. To that end, we induced repeated liver injuries over ten weeks in a mouse model injecting carbon tetrachloride (CCl4) twice a week. We lost 10% of the study animals within the first six weeks, which was accompanied by a steady deposition of extracellular matrix (ECM) regardless of metabolic activity of the liver. From week six onwards, all mice survived, and in these mice ECM deposition was rather reduced suggesting ECM remodelling as a liver response contributing to better coping with repeated injuries. The data of time-resolved paired transcriptome and proteome profiling of 18 mice was subjected to multi-level network inference, using Knowledge guided Multi-Omics Network inference (KiMONo), identified multi-level key markers exclusively associated with the injury-tolerant liver response. Interestingly, pathways of cancer and inflammation were lighting up and were validated using independent data sets compiled of 1034 samples from publicly available human cohorts. Interestingly, a yet undescribed link to lipid metabolism in this damage-tolerant phase was identified. Immunostaining revealed an unexpected accumulation of small lipid droplets (microvesicular steatosis) in parallel to a recovery of catabolic processes of the liver to pre-injury levels. Further, mild inflammation was experimentally validated. Taken together, we identified week six as a critical time point to switch the liver response program from an acute response that fosters ECM accumulation to a tolerant “survival” phase with pronounced deposition of small lipid droplets in hepatocytes potentially protecting against the repetitive injury with toxic chemicals. Our data suggest that microsteatosis formation plus a mild inflammatory state represent biomarkers and probably functional liver requirements to resist chronic damage.
Project description:Gene expression profiling was carried out in two liver tumors and one normal liver isolated from β2SP+/-; SMAD3+/- mice, and one normal liver isolated from wild type mouse. Whole-transcriptome sequencing of these 4 liver tissues.