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.
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.
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View SamplesThe transcriptional effects of urocortin I, urocortin II and tempol were compared to saline treatment in a rat model of in vivo coronary artery occlusion model of ischaemia/reperfusion injury of 25 min ischaemia and 2 hr reperfusion. <br></br>The treatment groups were as follows (i) sham operation or LAD occlusion with infusion of (ii) saline, (iii) 15 ?g/kg Ucn I, (iv) 15 ?g/kg Ucn II and (v) 100 mg/kg tempo infused just prior to reperfusionl.<br></br>Following 2 hr reperfusion the left ventricle was removed, snap frozen, followed by RNA extraction.
New targets of urocortin-mediated cardioprotection.
Sex, Age, Specimen part, Disease, Disease stage, Subject, Compound, Time
View SamplesWe sought to identify critical factors regulating muscle stem cell activation and commitment, and determined through loss-of-function analyses that HMGA2 (high mobility group AT-hook 2) is a key regulator of myogenesis both in vitro and in vivo.
An HMGA2-IGF2BP2 axis regulates myoblast proliferation and myogenesis.
Sex, Specimen part
View SamplesAncestral 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.
Epigenetic transgenerational inheritance of altered stress responses.
Sex, Specimen part
View SamplesDisuse atrophy is a common clinical phenomenon which significantly impacts muscle function and activities of daily living. In this study, we did expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse.
Transcriptional pathways associated with skeletal muscle disuse atrophy in humans.
Disease, Disease stage
View SamplesThe identification of genes that contribute to the biological basis for clinical heterogeneity and progression of prostate cancer is critical to accurate classification and appropriate therapy. We performed a comprehensive gene expression analysis of prostate cancer using oligonucleotide arrays with 63,175 probe sets to identify genes and expressed sequences with strong and uniform differential expression between nonrecurrent primary prostate cancers and metastatic prostate cancers. The mean expression value for >3,000 tumor-intrinsic genes differed by at least 3-fold between the two groups. This includes many novel ESTs not previously implicated in prostate cancer progression. Many differentially expressed genes participate in biological processes that may contribute to the clinical phenotype. One example was a strong correlation between high proliferation rates in metastatic cancers and overexpression of genes that participate in cell cycle regulation, DNA replication, and DNA repair. Other functional categories of differentially expressed genes included transcriptional regulation, signaling, signal transduction, cell structure, and motility. These differentially expressed genes reflect critical cellular activities that contribute to clinical heterogeneity and provide diagnostic and therapeutic targets.
Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesTriplicate experiments from T98G cells under asynchronously growing, and growth arrest by serum deprivation and contact inhibition.
A common set of gene regulatory networks links metabolism and growth inhibition.
No sample metadata fields
View SamplesWe performed single-cell and bulk transcriptome profiling in two different human cell lines. We performed single-cell RNA sequencing in live and fixed cells. Overall design: Single cell RNA sequencing of live and fixed cells, bulk RNA sequencing in two cell lines.
Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms.
No sample metadata fields
View SamplesmRNA expression from adenomas of patients with Lynch Syndrome and Familial Adenomatous Polyposis Overall design: 24 adenoma samples analyzed
Immune Profiling of Premalignant Lesions in Patients With Lynch Syndrome.
Specimen part, Subject
View SamplesCD133+ and CD133- cells were FACS islated from GBML8 cells to find gene signatures upregulated in cancer stem cells Overall design: After surface immuno staining, CD133+ and CD133- cells were FACS isolated and subjected to RNA isolation. Experiment represent averaged data of 2 independent FACS isolations.
GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth.
Specimen part, Subject
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