Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters. Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation.
Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways.
Sex, Specimen part
View SamplesSomatic cell nuclear transfer (SCNT) and induced pluripotent stem cells (iPSCs) represent two major approaches for somatic cell reprogramming. However, little attention has been paid to the ability of these two strategies in rejuvenating cells from donors with aging associated syndrome. Here, we utilized telomerase deficient (Terc-/-) mice to probe this question. SCNT-derived embryonic stem cells (ntESCs) and iPSCs were successfully derived from second generation (G2) and third generation (G3) of Terc-/- mice, and ntESCs showed better differentiation potential and self-renewal ability. Telomeres lengthened extensively in cloned embryos while remained or slightly increased in the process of iPSCs induction. Furthermore, G3 ntESCs exhibited improvement of telomere capping function as evidenced by decreased signal free ends and chromosome end-to-end fusion events. In contrast, there was a further decline of telomere capping function in G3 iPSCs. In addition to telomere dysfunction, mitochondria function was severely impaired in G3 iPSCs as evidenced by oxygen consumption rate (OCR) decline, reactive oxygen species (ROS) accumulation and dramatically increased mitochondria genome mutations while these deficiencies were greatly mitigated in G3 ntESCs. Our data proved the principle that SCNT-mediated reprogramming appears more superior than transcription factors induced reprogramming in terms of the resetting of telomere quality and mitochondria function, and thus, providing valuable information for further improvement of transcription factors mediated reprogramming.
Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells.
Specimen part
View SamplesAnalysis of global gene expression profiles of FACS-sorted, human Ad5- and CMV-specific CD4 T cells from the same PBMC sample of healthy donros, using affymetrix Human Gene 2.0ST Gene-Chips;
Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals.
Specimen part, Subject
View SamplesGene expression analysis identified 27 of these 744 p300 and pol II associated genes as significantly increased (p 0.05) within the first hour following mitogen stimulation
Dynamic bookmarking of primary response genes by p300 and RNA polymerase II complexes.
No sample metadata fields
View SamplesDifferential gene expression profiling in KMT2D-depleted MIA PaCa-2 cells was performed using Human Genome U133 Plus 2.0 Array
Lysine methyltransferase 2D regulates pancreatic carcinogenesis through metabolic reprogramming.
Treatment
View SamplesTightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases. Overall design: Comparison of gene expression at different stages of keratinocyte differentiation
Genome-wide p63-regulated gene expression in differentiating epidermal keratinocytes.
No sample metadata fields
View SamplesCarboplatin and paclitaxel are the most widely prescribed chemotherapeutic agents for ovarian cancer. Not all patients respond to treatment, so there is a need for biomarkers that reliably predict resistance in ovarian tumors. Expression of such biomarkers may be dynamically controlled. Gene expression was assessed for a period of 14 days after treatment with carboplatin or combined carboplatin-paclitaxel in xenografts from two ovarian cancer models: chemosensitive serous adenocarcinoma derived OV1002 and slow growing, chemoresistant HOX424 of clear cell origin. Tumour volume reduction was observed in both cell lines post treatment, with a more prominent effect in OV1002, which subsided in late time points. In OV1002, hierarchical clustering classified differentially expressed genes into four time-related patterns, upregulated and downregulated groups for each early and late expressed genes. Upregulated genes were involved in DNA repair, cell cycle and apoptosis, while downregulated groups were involved in oxygen consuming metabolic processes and apoptosis control. Carboplatin-paclitaxel treatment triggered a more comprehensive response. HOX424 responded only to the combined treatment, while the observed reduction in tumour growth was limited. Several apoptosis and cell cycle genes were upregulated, while Wnt signaling was downregulated in the exclusively late expression pattern observed in this cell line. Late downregulated gene groups post carboplatin-taxane treatment were capable of predicting overall survival in two independent clinical datesets. Pathways overrepresented in these clusters were also predictive of outcome. This longitudinal gene expression study may help characterization of chemotherapy response, identification of resistance biomarkers and guiding timing of biopsies.
Chemotherapy-induced dynamic gene expression changes in vivo are prognostic in ovarian cancer.
Disease, Disease stage, Time
View SamplesAnalysis of the gene expression pattern in the caput, corpus and cauda epididymides of three donors of 26-50 years of age with no medical pathologies that could affect reproductive function. The data generated in this study demonstrate a region specific gene expression pattern along the human epididymis that seems to coincide with the morphological distinctive features of the excurrent duct.
Region-specific gene expression profiling along the human epididymis.
No sample metadata fields
View SamplesThe PI3K/mammalian target of rapamycin (mTOR) pathway is dysregulated in over 50% of human GBM but remains a challenging clinical target. Inhibitors against PI3K/mTOR mediators have limited clinical efficacy as single agents. Gene expression profiling after PI3K/mTOR inhibition treatment was analyzed by Affymetrix microarrays.
MSK1-Mediated β-Catenin Phosphorylation Confers Resistance to PI3K/mTOR Inhibitors in Glioblastoma.
Specimen part, Cell line
View SamplesWorldwide, almost 100 millions men rely on vasectomy for male contraceptive purposes. Due to changes in their personal life, an increasing number of these men request surgical vasectomy reversal. Unfortunately, a significant proportion of these men remain infertile, despite the reestablishment of patent ducts, possibly due to epididymal damages caused by vasectomy. In animal models, vasectomy affects different epididymal physiological and biochemical parameters. However, consequences of vasectomy on these biochemical parameters are poorly understood at the molecular level. Furthermore, results obtained with animal models cannot by extrapolated to human to understand the consequences of vasectomy on epididymal functions. Gene expression pattern of epididimydis is highly regulated. We previously showed that the human epididymal expression pattern of two genes is altered under vasectomy. To complete the list of epididymal genes affected by vasectomy, we analysed the epididymal gene expression profile of three vasectomised donors, using the affymetrix human GeneChip U133 Plus 2. These results were compared with gene expression pattern of three normal donors. The data generated allowed the identification of many human epididymal genes for which the expression is modified under vasectomy. Qt-PCR and western-blot analysis of six selected genes known to be expressed in specific epididymal segments were performed. The Qt-PCR results confirmed the selected transcripts expression pattern deduced from microarrays data, while the western-blot analysis revealed some differences in protein distribution along the epididymis when compared to the transcripts expression pattern. These results contribute to the understanding of the causes of the persistent of infertility even though spermogram values suggest surgical success of vasovasostomy.
Effects of vasectomy on gene expression profiling along the human epididymis.
No sample metadata fields
View Samples