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GSE81964
Mus musculus
30 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.
Publication Title
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Medulloblastoma (MB), a tumor of the cerebellum, is the most common malignant brain tumor in children. One third of all human MB exhibits a gene expression signature of Sonic hedgehog (Shh) signaling. Hedgehog (Hh) pathway inhibitors have shown efficacy in clinical trials for MB, however, tumors develop resistance to these compounds, highlighting the need to identify additional therapeutic targets for treatment. We have identified a role for Norrin signaling in tumor initiation in the Patched (Ptch) mouse model of MB. Norrin is a secreted factor that functions as an atypical Wnt by binding to the Frizzled4 (Fzd4) receptor on endothelial cells to activate canonical beta-catenin-mediated Wnt signaling pathway. In the cerebellum, activation of Norrin/Fzd4 signaling is required for the establishment and maintenance of the blood brain barrier (BBB). We have identified a role for Norrin signaling in the stroma as a potent tumor inhibitory signal. Inactivation of Norrin in Ptch+/- mice significantly shortens latency and increases MB incidence. This phenotype is associated with an increased frequency of pre-tumor lesions and their conversion to malignancy. In this context, loss of Norrin signalling in endothelial cells is associated with an accelerated transition to a pro-tumor stroma characterized by vascular permeability, inflammation and angiogenic remodelling. Accordingly, loss of Ndp significantly alters the stromal gene expression signature of established Ptch MB.
Publication Title
Norrin/Frizzled4 signalling in the preneoplastic niche blocks medulloblastoma initiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Bone marrow mesenchymal stem cells (MSC) were adipogenically differentiated followed by dedifferentiation. We are interested to know the new fat markers, adipogenic signaling pathways and dedifferentiation signaling pathways.Furthermore we are also intrested to know that how differentiated cells convert into dedifferentiated progenitor cells. To address these questions, MSC were adipogenically differentiated, followed by dedifferentiation. Finally these dedifferentiated cells were used for adipogenesis, osteogenesis and chondrogenesis. Histology, FACS, qPCR and GeneChip analyses of undifferentiated, adipogenically differentiated and dedifferentiated cells were performed. Regarding the conversion of adipogenically differentiated cells into dedifferentiated cells, gene profiling and bioinformatics demonstrated that upregulation (DHCR24, G0S2, MAP2K6, SESN3) and downregulation (DST, KAT2, MLL5, RB1, SMAD3, ZAK) of distinct genes play a curcial role in cell cycle to drive the adipogenically differentiated cells towards an arrested state to narrow down the lineage potency. However, the upregulation (CCND1, CHEK, HGF, HMGA2, SMAD3) and downregulation (CCPG1, RASSF4, RGS2) of these cell cycle genes motivates dedifferentiation of adipogenically differentiated cells to reverse the arrested state. We also found new fat markers along with signaling pathways for adipogenically differentiated and dedifferentiated cells, and also observed the influencing role of proliferation associated genes in cell cycle arrest and progression.
Publication Title
Transdifferentiation of adipogenically differentiated cells into osteogenically or chondrogenically differentiated cells: phenotype switching via dedifferentiation.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 10 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
In the present study, transcript profiling was carried out in the liver samples from wk 5 of lactation in order to identify genes and pathways regulated by rumen-protected CLA during early lactation. The first wks after parturition represent a critical phase in the productive cycle of high-yielding dairy cows because the liver experiences pronounced metabolic and inflammatory stress which increases the risk to develop liver-associated diseases, such as fatty liver and ketosis.
Publication Title
Transcript profiling in the liver of early-lactating dairy cows fed conjugated linoleic acid.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Autologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However, patients with osteoarthritis (OA) are lacking an appropriate long-lasting treatment alternative, partly since it is not known if chondrocytes from OA patients have the same chondrogenic differentiation potential as chondrocytes from donors not affected by OA. Articular chondrocytes from patients with OA undergoing total knee replacement (Mankin Score >3, Ahlbck Score >2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and scaffold (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene expression profiling using genome-wide oligonucleotide microarrays. Expression data were verified by using quantitative RT-PCR. Chondrocytes from ND and OA donors demonstrated accumulation of comparable amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (COL2A1, COMP, aggrecan, CRTL1, SOX9) and genes involved in matrix synthesis (biglycan, COL9A2, COL11A1, TIMP4, CILP2) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (COL10A1, RUNX2, periostin, ALP, PTHR1, MMP13, COL1A1, COL3A1) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, were differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and only 184 genes were differentially regulated. Only few genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings suggest that the chondrogenic capacity is not significantly affected by OA and OA chondrocytes fulfill the requirements for matrix-associated ACT.
Publication Title
Chondrogenic differentiation potential of osteoarthritic chondrocytes and their possible use in matrix-associated autologous chondrocyte transplantation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Nrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in lung cancer.
Publication Title
Dimethyl fumarate and the oleanane triterpenoids, CDDO-imidazolide and CDDO-methyl ester, both activate the Nrf2 pathway but have opposite effects in the A/J model of lung carcinogenesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Sus scrofa
- 4 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Carnitine is a water soluble quaternary amine which is essential for normal function of all tissues.
Publication Title
Effect of L-carnitine on the hepatic transcript profile in piglets as animal model.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Bos taurus
- 12 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
As polyphenols are exerting a broad spectrum of metabolic effects, we hypothesize that feeding of GSGME might influence other metabolic pathways in the liver which could account for the positive effects of GSGME observed in cows during early lactation. In order to investigate this hypothesis, we used using a genome-wide transcript profiling technique to explore changes in the hepatic transcriptome of cows supplemented with GSGME during the transition period. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts (fold change > 1.3 or < -1.3, P < 0.05), from which 156 (155 mRNAs, 1 miRNA) were up- and 51 (43 mRNAs, 8 miRNAs) were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation, such as M phase, cell cycle phase, mitotic cell phase and microtubule cytoskeleton and the most enriched KEGG database pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that 13 genes (XBP1, HSPA5, HERPUD1, DNAJC5G, CALR, PDIA4, DNAJB11, PHLDA1, PPP1R3C, GADD45B, BAG3, HYOU1, MANF) are involved in ER stress-induced UPR. Moreover, several of the down-regulated mRNAs, like CXCL14 and CCL3L1L and the acute phase protein SAA4, play an important role in inflammatory processes. Accordingly, protein folding, response to unfolded protein, response to protein stimulus, unfolded protein binding, chemokine activity, chemokine receptor binding and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins SAA and haptoglobin were reduced in cows fed GSGME compared to control cows. Collectively, our findings from transcriptome analysis of down-regulated mRNAs and functional analysis of mRNAs targeted by the up-regulated mir-376c clearly indicate that GSGME is able to inhibit inflammatory processes and ER stress in the liver of dairy cows during early lactation. Moreover, our findings indicate that at least some of the GSGME effects on the hepatic transcriptome of dairy cows are mediated by miRNA-mRNA interactions.
Publication Title
Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract.
Sample Metadata Fields
Sex, Specimen part
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Background: While the mechanisms underlying the lactation-induced adaptations of intermediary metabolism and immune response have been extensively studied in rodents and dairy cows, little is known in this regard in sows. Therefore, the present study aimed to explore the lactation-induced changes in hepatic gene expression in sows during lactation.
Publication Title
Genome-wide transcript profiling indicates induction of energy-generating pathways and an adaptive immune response in the liver of sows during lactation.
Sample Metadata Fields
Sex, Specimen part
View Samples