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Homo sapiens
12 Downloadable Samples
Illumina human-6 v2.0 expression beadchip
Description
PRC, a member of the PGC-1 coactivator family, is responsive to serum growth factors and up regulated in proliferating cells. Here, we investigated its in vivo role by stably silencing PRC expression with two different short hairpin RNAs (shRNA#1 and shRNA#4) that were lentivirally introduced into U2OS cells. ShRNA#1 transductants exhibited nearly complete knockdown of PRC protein whereas shRNA#4 transductants expressed PRC protein at approximately 15 percent of the control level. Complete PRC silencing by shRNA#1 resulted in a severe inhibition of respiratory growth, reduced expression of respiratory protein subunits from complexes I, II, III and IV, markedly lower complex I and IV respiratory enzyme levels and diminished mitochondrial ATP production. Surprisingly, shRNA#1 transductants exhibited a striking proliferation of abnormal mitochondria that were devoid of organized cristae and displayed severe membrane abnormalities. Although shRNA#4 transductants had normal respiratory subunit expression and a moderately diminished respiratory growth rate, both transductants showed markedly reduced growth on glucose accompanied by inhibition of G1/S cell cycle progression. Microarray analysis revealed striking overlaps in the genes affected by PRC silencing in the two transductants and the functional identities of these overlapping genes were consistent with the observed mitochondrial and cell growth phenotypes. The consistency between phenotype and PRC expression levels in the two independent transductant lines argues that the defects result from PRC silencing and not from off target effects. These results support a role for PRC in the integration of pathways directing mitochondrial respiratory function and cell growth.
Publication Title
Short hairpin RNA-mediated silencing of PRC (PGC-1-related coactivator) results in a severe respiratory chain deficiency associated with the proliferation of aberrant mitochondria.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 380 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sleep and affective behaviors are highly interrelated phenotypes, commonly altered in a variety of neuropsychiatric diseases, including major depressive disorder (MDD). To understand the transcriptomic organization underlying sleep and affective function, we studied a population of (C57BL/6J x 129S1/SvImJ) F2 mice by measuring 283 affective and sleep phenotypes and profiling gene expression across four brain regions, including the frontal cortex, hippocampus, thalamus, and hypothalamus. We identified converging molecular bases for sleep and affective phenotypes at both the single-gene and gene-network levels. Utilizing publicly available transcriptomic datasets collected from sleep-deprived mice and major depressive disorder (MDD) patients, we identified three cortical gene networks altered by sleep/wake changes and depression. The network-level actions of sleep loss and depression were opposite to each other, providing a mechanistic basis for the sleep disruptions commonly observed in depression as well as the reported acute antidepressant effects of sleep deprivation. We highlight one particular network composed of circadian rhythm regulators and neuronal activity-dependent immediate-early genes. The key upstream driver of this network, Arc, may act as a nexus linking sleep and depression. Our data provide mechanistic insights into the role of sleep in affective function and MDD.
Publication Title
Cross-species systems analysis identifies gene networks differentially altered by sleep loss and depression.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative splicing is a key event to human transcriptome and proteome diversity and complexity. Recent evidence suggests that pancreatic cancer might possess particular patterns of splice variation that influence the function of individual genes contributing to tumour progression in this disease. The identification of new pancreatic cancer-associated splice variants would offer opportunities for novel diagnostics and potentially also represent novel therapeutic targets.
Publication Title
Splice variants as novel targets in pancreatic ductal adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 48 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Ancestral environmental exposures that promote epigenetic transgenerational inheritance influence all aspects of an individuals life history. Stress experienced during adolescence can affect adult physiological and behavioural phenotypes. The current study utilized a systems biology approach to investigate the interactions of these two forms of epigenetic modification, one carried in the germline transgenerationally and the other contained in the context of life history. A transgenerational epigenetic imprint left by the fungicide vinclozolin promoted regional specific brain gene networks that influenced chronic restraint stress responses to alter adult physiological, brain and behavioural phenotypes. The environmentally-induced epigenetic transgenerational inheritance was found to interact with early life stress response to impact the adult brain genome activity to bring the phenotype into being.
Publication Title
Epigenetic transgenerational inheritance of altered stress responses.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 70 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st), Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative splicing is a key event to human transcriptome and proteome diversity and complexity. Recent evidence suggests that pancreatic cancer might possess particular patterns of splice variation that influence the function of individual genes contributing to tumour progression in this disease. The identification of new pancreatic cancer-associated splice variants would offer opportunities for novel diagnostics and potentially also represent novel therapeutic targets.
Publication Title
A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples
GSE1692- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Triplicate experiments from T98G cells under asynchronously growing, and growth arrest by serum deprivation and contact inhibition.
Publication Title
A common set of gene regulatory networks links metabolism and growth inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Several studies demonstrated IgVH mutation status and ZAP-70 expression as the most relevant prognostic markers in CLL, suggesting the separation of two patient subgroups: with good (MTZAP-70-) and poor prognosis (UMZAP-70+). We determined gene expression of B cells in 112 CLL patients divided into three classes: the first with IgVHMT and ZAP-70-, the second with IgVHUM and ZAP-70+, and the third included both IgVHUM ZAP-70- and IgVHMT ZAP-70+. We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in lipid (glycerolipid/glycerophospholipid) metabolism overexpressed in UMZAP-70+. In addition, this study demonstrates the role of ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP-70+ in respect to MTZAP-70-. ARSD protein was found at significantly higher concentrations in UMZAP-70+ compared to MTZAP-70- CLL B cells and B cells from healthy individuals by Western blotting. Statistical analysis identified a strong correlation between ARSD and IgVH mutation status; ARSD protein level was associated with the requirement of therapy for CLL patients and for this purpose it is as good as IgVH mutational status. Our study highlights ARSD as a promising new prognostic factor in CLL and sphingolipid metabolism as a putative new biological mechanism in CLL.
Publication Title
Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Arp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes'' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. Overall design: Gene expression profile of wt and ARPC4 ko epidermis
Publication Title
Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
Arp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes'' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. Overall design: Gene expression profile of wt, ARPC4 ko and EGFP-Nrf2 expressing keratinocytes.
Publication Title
Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples