The objective of this study was to elucidate age-related differences in gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells (rhMSC) obtained from fetal, infant, and adult donors relevant to their growth and other properties. Although a high degree of similarity was observed in the rhMSC gene expression profiles when comparing the three age groups, significant differences were found that strongly parallel gene expression profiles of human MSC. The potential functional relevance of differential gene expression was most apparent when comparing fetal and adult rhMSC transcript profiles. Overall, the observed gene expression profiles are consistent with a loss of rhMSC pluripotency and proliferative capacity with advancing donor age. In addition, these data highlight the importance of use of non-human primates as a model system for studying the properties of human stem cells.
Age-related gene expression profiles of rhesus monkey bone marrow-derived mesenchymal stem cells.
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Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
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View SamplesTwo rat hepatic cell lines, WB-F344 and WB311, were characterized for the effect of rapamycin on gene expression. The WB311 cell line, which is tumorigenic and resistant to the growth inhibitory effects of rapamycin, was originally derived from the WB-F344 parental hepatic epithelial cell line. The goal of this experiment was to identify genes that responded to rapamycin in the sensitive cells but not the resistant cells, thereby providing insight into the mechanism of rapamycin resistance.
Rapamycin response in tumorigenic and non-tumorigenic hepatic cell lines.
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View SamplesThe goal is to examine the transcriptome of ESCs with different Myc levels Overall design: In order to analyse the transcriptome, mESC population was sorted in 3 groups depending on Myc levels
Pluripotency Surveillance by Myc-Driven Competitive Elimination of Differentiating Cells.
Specimen part, Cell line, Subject
View SamplesThe goal of this study is to analyse the transcriptome of WT and Myc-overexpressing ESCs in iMOS T1-Myc mosaic cultures. Overall design: Homozygous iMOS T1-Myc ESC cultures (Claveria et al., 2013) were treated with 20µM 4-hydroxytamoxifen for 24 hours to generate a mosaic of cell populations containing two, one or no extra Myc and EYFP copies. 24 hours after tamoxifen removal, cells were sorted according to their EYFP expression levels and populations with two extra Myc and EYFP copies and with no extra Myc and EYFP copies were collected. Uninduced homozygous iMOS T1-Myc ESC cultures were also sorted and collected as a control. Three biological replicas were included for each condition.
Pluripotency Surveillance by Myc-Driven Competitive Elimination of Differentiating Cells.
Subject
View SamplesNa+/I- symporter (NIS)-mediated iodide uptake allows radioiodine therapy for thyroid cancer. NIS is also expressed in breast tumors, raising potential for radionuclide therapy of breast cancer. However, NIS expression in most breast cancers is low and may not be sufficient for radionuclide therapy. A better understanding of the mechanisms of NIS regulation in breast cancer may lead to strategies for increasing cell surface NIS and radioactive iodide uptake (RAIU) in breast cancer. The MCF-7 cell line is the only human breast cancer cell line with inducible endogenous NIS expression. Kogai et al. [2000] first reported that trans-retinoic acid (tRA) induces NIS mRNA expression in MCF-7 cells and it was later reported that a combination treatment of tRA and hydrocortisone (tRA/H) further increases tRA-induced NIS expression/function in MCF-7 cells (Kogai et al., 2005; Dohan et al., 2006). In this study, we used gene expression profiling to identify genes that correlate with NIS expression in MCF-7 cells such that mechanisms underlying NIS modulation may be elucidated.
Microarray analysis of genes associated with cell surface NIS protein levels in breast cancer.
Specimen part, Cell line
View SamplesHow chromatin controls transcription elongation and splicing is an open question. Here we determine the transcriptomic changes of cells partially depleted of core histones. For that we construct a cell line with Doxycycline-controlled levels of the histone regulatory protein SLBP (HCT-shSLBP). HCT-shSLBP is derived from the human colon cancer cell line HCT116.
Defective histone supply causes changes in RNA polymerase II elongation rate and cotranscriptional pre-mRNA splicing.
Specimen part, Cell line
View SamplesWe report a new protein complex with a role in transcription elongation that is formed by Ypr045c (Thp3) and the Csn12 component of the COP9-signalosome. Thp3-Csn12 is recruited to transcribed genes. Their mutations suppress the gene expression defects of mutants of the THO complex involved in mRNP biogenesis and export and show defects in mRNA accumulation. In vivo transcription elongation impairment of thp3 mutants is shown by reduction of RNAPII recruitment throughout an active gene and in transcript run on analysis performed in G-less systems. This new complex establishes a novel link between transcription and mRNA processing.
New suppressors of THO mutations identify Thp3 (Ypr045c)-Csn12 as a protein complex involved in transcription elongation.
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View SamplesThe epigenetic changes of the chromatin represent an attractive molecular substrate for adaptation to the environment. We examined here the role of CBP, a histone acetyltransferase involved in mental retardation, in the genesis and maintenance of long-lasting systemic and behavioral adaptations to environmental enrichment (EE). Morphological and behavioral analyses demonstrated that EE ameliorates deficits associated to CBP-deficiency. However, CBP-deficient mice also showed a strong defect in environment-induced neurogenesis and impaired EE-enhanced spatial navigation and patter separation ability. These defects correlated with an attenuation of the transcriptional program induced in response to EE and with deficits in histone acetylation at the promoters of EE-regulated, neurogenesis-related genes. Additional experiments in CBP restricted and inducible knockout mice indicated that environment-induced adult neurogenesis is extrinsically regulated by CBP function in mature granule cells. Overall, our experiments demonstrate that the environment alters gene expression by impinging on activities involved in modifying the epigenome and identify CBP-dependent transcriptional neuroadaptation as an important mediator of EE-induced benefits, a finding with important implications for mental retardation therapeutics.
CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement.
Sex, Age, Specimen part
View SamplesPurpose: To identify differntially expressed transcripts in TP-0903 treated embryos that impair cranila NC EMT and cell migration in zebrafish embryos Methods: zebrafish embryos treated at 13 hpf with 5-7uM TP-0903 and DMSO for 1-, 4- and 8-hrs at 28°C. 35 embryos were collected for each treatment. Results: TP-0903 increases expression of several retinoic acid target genes including genes from within the retinoid pathway Conclusions: TP-0903 causes a direct increase in RA signaling that impairs cranial NC EMT and cell migration in zebrafihs embryos Overall design: mRNA profiles of zebrafish embryos treated with TP-0903 and DMSO were generated by RNA-Seq, in quadruplicates, using Illumina Hi Seq
Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis.
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