The liver has inherent regenerative capacity via mitotic division of mature hepatocytes. However, if the hepatic loss is massive or mature hepatocyte proliferation is impaired by chronic liver injury, HSPC are activated to support liver regeneration. Access to liver tissue from 4 patients who underwent liver transplantation for hepatitis B virus (HBV)- associated acute liver failure (ALF) provided us with the opportunity to investigate the molecular mechanisms of liver regeneration in humans by means of gene expression profiling and immunohistochemistry (IHC). Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual liver specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two-well defined clusters that segregated according to the histopathological severity, i.e. massive hepatic necrosis (MHN; 2 patients) and submassive hepatic necrosis (SHN; 2 patients). We found that ALF is characterized by a strong hepatic stem/progenitor cell (HSPC) gene signature, as also confirmed by IHC, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of cancer stem cell genes (EpCAM, CK19 and CK7), whereas the most upregulated genes in SHN were related to cellular growth and proliferation (AKR1B10, NQO1, RRM2, SFN, TOP2A, CCNB1, CDC20, ANLN and KI67). The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound healing process. Conclusion: Our data provide evidence of marked HSPC cell activation and fibrogenesis in HBV-associated ALF, which positively correlate with the extent of liver necrosis. Moreover, we detected a strong tumorigenesis gene signature in ALF, which underlines the relationship between liver regeneration and liver cancer.
Liver regeneration signature in hepatitis B virus (HBV)-associated acute liver failure identified by gene expression profiling.
Specimen part, Disease, Disease stage, Subject
View SamplesDentatorubral-pallidoluysian Atrophy (DRPLA) is a human polyQ disease caused by the expansion of a CAG strech in the atrophin-1 (at-1) gene. In all vertebrates, a second atrophin gene (at-2) is present and it encodes a related protein void of polyQ tracks. In D.melanogaster there is one conserved Atrophin (Atro) gene, ubiquitously expressed, which contains all functional domains of vertebrate Atrophins, including two polyQ stretches. To understand to what extent transcriptional alterations cause neurodegeneration and are linked to the normal functions of Atrophin, we performed a genome wide transcriptional profiling in our Drosophila models, focusing on primary events that precede neurodegeneration.
Polyglutamine Atrophin provokes neurodegeneration in Drosophila by repressing fat.
No sample metadata fields
View SamplesMitochondrial dysfunction causes biophysical, metabolic and signalling changes that alter homeostasis and reprogram cells. We used a Drosophila model in which TFAM is overexpressed in the nervous system with or without Ras/MAPK pathway inhibition, by knock-down of the ETS transcription factor pointed, to investigate the how mitochondrial dysfunction and Ras/MAPK signalling affect the transcriptome.
Ras-ERK-ETS inhibition alleviates neuronal mitochondrial dysfunction by reprogramming mitochondrial retrograde signaling.
Specimen part
View SamplesDigital gene expression profiling was used to invesigate the differetiated genes between primary mouse hepatic stellate cells infected with AGGF1 adenovirus particles or negative control adenovirus pairticles. Overall design: Primary hepatic stellate cells isolated from mice were cultured in vitro, infected with AGGF1 adenovirus particles or negative control adenovirus particles, at day 8, total RNA were prepared and used for digital gene expression tag profiling.
Angiogenic factor with G patch and FHA domains 1 (Aggf1) regulates liver fibrosis by modulating TGF-β signaling.
Specimen part, Cell line, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Specimen part, Time
View SamplesTo find regulated genes during peak inflammation of rheumatoid arthritis (RA), we have collected synovium from mouse Serum Transfer Arthtitis (STA) model at day 0 (Non Arthritic) and day 10 (Peak Inflammation).
Synovium-Derived MicroRNAs Regulate Bone Pathways in Rheumatoid Arthritis.
Specimen part, Time
View SamplesRibosome profiling of MDA-MB-231 cells treated with Silvestrol to monitor transcriptome wide, eIF4A-dependent changes in translation efficiency Overall design: Translation efficiency (TE) of mRNAs dervied from ribosome footprints was monitored in the presence or absence of 25 nM Silvestrol, an inhibitor of eukaryotic translation initiation factor 4A (eIF4A). Transcripts with reduced TE in the presence of Silvestrol were compare to transcripts with reduced TE in the presence of INK128, a catalytic mTOR inhbitor.
Transcriptome-wide characterization of the eIF4A signature highlights plasticity in translation regulation.
No sample metadata fields
View SamplesThe growth and fruit quality of grapevine are widely affected by abnormal climatic conditions such as water deficit. But how grapevine responds to drought stress is still largely unknown. Here we found that VaNAC26, a member of NAC transcription factor family, was up-regulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardiness wild Vitis species. Ectopic overexpression of VaNAC26 enhanced the drought and salt tolerances in transgenic Arabidopsis. Higher activities of antioxidant enzymes and the lower concentration of H2O2 and O2- were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicate that the reactive oxygen species (ROS) scavenging was enhanced by VaNAC26 in transgenic lines. Microarray based transcriptome analysis reveals that genes related to jasmonic acid (JA) synthesis and signaling were up-regulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on NACRS motif, which was broadly existent in the promoter regions of up-regulated genes in transgenic lines. Endogenous JA content was found increased obviously in VaNAC26-OE-2/3 lines. Our data suggests that VaNAC26 responds to abiotic stresses and may enhance the drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.
Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.
Specimen part
View SamplesThe Brakeless protein performs many important functions during Drosophila development, but how it controls gene expression is not understood. We previously showed that Brakeless can function as a transcriptional co-repressor. Here, we report transcriptional profiling of brakeless mutant embryos to identify additional target genes.
The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos.
Specimen part
View SamplesAbraxane, a nanoparticle (NP) formulation of paclitaxel (PTX), has been demonstrated to be more effective than Taxol, the small molecule formulation, for the treatment of breast cancer and non-small cell lung cancer (NSCLC). It was reported that Abraxane existed in plasma as particles with the size of ~10 nm. NPs get in and out of the cells by endocytosis and exocytosis, whereas small molecules by diffusion and efflux. It is intriguing to know whether the improved pharmaceutical performance is related to the “too-big-to-be-pumped-out” phenomenon. Here we established an Abraxane-resistant NSCLC cell line A549/Abr and compared its transcriptomes with that of the Abraxane-sensitive parental cell line by RNA-Seq technology. To our surprise, the most significantly up-regulated genes were ABC transporters, the common efflux pump for small molecules. We further found that the ABCB1 inhibitor Verapamil reversed the drug resistance and confirmed the important role of ABCB1 in Abraxane resistance. Overall design: mRNA profiles of A549 and A549/Abr cells were generated using Illumina Hiseq 2000 and compared.
Abraxane, the Nanoparticle Formulation of Paclitaxel Can Induce Drug Resistance by Up-Regulation of P-gp.
No sample metadata fields
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