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Mus musculus
8 Downloadable Samples
NextSeq 500
Description
This study aimed to explore the role of NIPP1 in adult germline cell proliferation and differentiation, using a ubiquitous inducible NIPP1 knockout (TKO) mouse model. To gain unbiased insight into the molecular mechanism that underly the sertoli-only phenotype in TKO, we performed a comparative RNA sequencing profiling of control and TKO, in which NIPP1 was tamoxifin-induced depleted. Overall design: Two genotypes are compared after treatment with tamoxifen. The control genotype (UBC CRE-ERT2+/- Ppp1r8 fl/+) looses the floxed allele of PPP1R8 (aka NIPP1) as a consequence of the treatment with tamoxifen and becomes heterozygous for PPP1R8. The KO genotype (UBC CRE-ERT2+/- Ppp1r8 fl/-) also looses the floxed allele of PPP1R8 as a consequence of the tamoxifen treatment and becomes homozygous KO. For each genotype, 4 replicates are profiled.
Publication Title
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Matrix metalloproteinase 7 (MMP7) is expressed at low levels in intact, normal airways by non-mucous-producing cells, including ciliated cells. In response to injury and infection, MMP7 expression is quickly and markedly upregulated and functions to regulate wound repair and various mucosal immune processes. We evaluated the global transcriptional response of airway epithelial cells from wild type and Mmp7-null mice cultured at an air-liquid interface. A common injury response was seen in both genotypes with up-regulation of genes associated with proliferation and migration. Analysis of differentially expressed genes between genotypes after injury revealed enrichment of functional categories associated with inflammation, cilia and differentiation. Because these analyses suggested MMP7 regulated ciliogenesis, we evaluated the recovery of the airway epithelium in wild type and Mmp7-null mice in vivo after naphthalene injury. These studies identified a new role for MMP7 in attenuating ciliogenesis during wound repair.
Publication Title
Matrix metalloproteinase-7 coordinates airway epithelial injury response and differentiation of ciliated cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of our study is to determine whether Atg16L1 deficiency leads to differences in the transcriptional profile of CD11c+ Dendritic Cells, ultimately leading to an increased inflammatory phenotype.
Publication Title
Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The goal of our study is to determine whether Atg16L1 deficiency leads to differences in the transcriptional profile of CD11c+ Dendritic Cells, ultimately leading to an increased inflammatory phenotype.
Publication Title
Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.
Sample Metadata Fields
Age, Specimen part
View Samples
GSE61561- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens, Saccharomyces cerevisiae
- 2 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The deafness gene DFNA5 induces programmed cell death through mitochondria and MAPK-related pathways.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Sorafenib leads to a survival benefit in patients with advanced hepatocellular carcinoma but its use is hampered by the occurrence of drug resistance. To investigate the molecular mechanisms involved we developed five resistant human liver cell lines in which we studied morphology, gene expression and invasive potential. The cells changed their appearance, lost E-cadherin and KRT19 and showed high expression of vimentin, indicating epithelial-to-mesenchymal transition. Resistant cells showed reduced adherent growth, became more invasive and lost liver-specific gene expression. Furthermore, following withdrawal of sorafenib, the resistant cells showed rebound growth, a phenomenon also found in patients. This cell model was further used to investigate strategies for restoration of sensitivity to sorafenib.
Publication Title
Long-term exposure to sorafenib of liver cancer cells induces resistance with epithelial-to-mesenchymal transition, increased invasion and risk of rebound growth.
Sample Metadata Fields
Cell line
View Samples GSE54257- Mus musculus, Homo sapiens
- 116 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 96 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Drug-induced liver injury (DILI) is an important clinical problem. Here we used a genomics approach to establish the critical drug-induced toxicity pathways that act in synergy with the pro-inflammatory cytokine tumor necrosis factor (TNF) to cause cell death of liver HepG2 cells. Transcriptomics of the cell injury stress response pathways initiated by two hepatoxicants, diclofenac and carbamazepine, revealed the endoplasmic reticulum (ER) stress/translational initiation signaling and Nrf2 antioxidant signaling as two major affected pathways, which was similar to that observed for the majority of ~80 DILI compounds in primary human hepatocytes. The ER stress was primarily related to PERK and ATF4 activation and subsequent expression of CHOP, which was all independent of TNF signaling. Identical ATF4 dependent transcriptional programs were observed in primary human hepatocytes as well as primary precision cut human liver slices. Targeted RNA interference studies revealed that while ER stress signaling through IRE1 and ATF6 acted cytoprotective, activation of the ER stress protein kinase PERK and subsequent expression of CHOP was pivotal for the onset of drug/TNF-induced apoptosis. While inhibition of the Nrf2-dependent adaptive oxidative stress response enhanced the drug/TNF cytotoxicity, Nrf2 signaling did not affect CHOP expression. Both hepatotoxic drugs enhanced expression of the translational initiation factor EIF4A1, which was essential for CHOP expression and drug/TNF-mediated cell killing. Our data support a model in which enhanced drug-induced translation initiates PERK-mediated CHOP signaling in an EIF4A1 dependent manner, thereby sensitizing towards caspase-8-dependent TNF induced apoptosis.
Publication Title
Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Drug-induced liver injury (DILI) is an important clinical problem. Here we used a genomics approach to establish the critical drug-induced toxicity pathways that act in synergy with the pro-inflammatory cytokine tumor necrosis factor (TNF) to cause cell death of liver HepG2 cells. Transcriptomics of the cell injury stress response pathways initiated by two hepatoxicants, diclofenac and carbamazepine, revealed the endoplasmic reticulum (ER) stress/translational initiation signaling and Nrf2 antioxidant signaling as two major affected pathways, which was similar to that observed for the majority of ~80 DILI compounds in primary human hepatocytes. The ER stress was primarily related to PERK and ATF4 activation and subsequent expression of CHOP, which was all independent of TNF signaling. Identical ATF4 dependent transcriptional programs were observed in primary human hepatocytes as well as primary precision cut human liver slices. Targeted RNA interference studies revealed that while ER stress signaling through IRE1 and ATF6 acted cytoprotective, activation of the ER stress protein kinase PERK and subsequent expression of CHOP was pivotal for the onset of drug/TNF-induced apoptosis. While inhibition of the Nrf2-dependent adaptive oxidative stress response enhanced the drug/TNF cytotoxicity, Nrf2 signaling did not affect CHOP expression. Both hepatotoxic drugs enhanced expression of the translational initiation factor EIF4A1, which was essential for CHOP expression and drug/TNF-mediated cell killing. Our data support a model in which enhanced drug-induced translation initiates PERK-mediated CHOP signaling in an EIF4A1 dependent manner, thereby sensitizing towards caspase-8-dependent TNF induced apoptosis.
Publication Title
Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNFα-mediated hepatotoxicity.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples