The adaptive mechanisms in response to excess energy supply are still poorly known in humans. Our aims were to define metabolic responses and changes in gene expression in adipose tissue of healthy volunteers during fat overfeeding.
Subcutaneous adipose tissue remodeling during the initial phase of weight gain induced by overfeeding in humans.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function.
Specimen part
View SamplesWe have analyzed gene expression in cone photoreceptors isolated from wild type and C-DGCR8 (DiGeorge Syndrome Critical Region Gene 8) KO mice at five different time points to get a mechanistic inside into the altered molecular pathways after microRNAs depletion.
miRNAs 182 and 183 are necessary to maintain adult cone photoreceptor outer segments and visual function.
Specimen part
View Samplesd-serine is naturally present throughout the human body. It is also used as add-on therapy for treatment-refractory schizophrenia. d-Serine interacts with the strychnine-insensitive glycine binding site of NMDA receptor, and this interaction could lead to potentially toxic activity (i.e., excitotoxicity) in brain tissue. The transcriptomic changes that occur in the brain after d-serine exposure have not been fully explored.
D-Serine exposure resulted in gene expression changes implicated in neurodegenerative disorders and neuronal dysfunction in male Fischer 344 rats.
Sex
View SamplesSkin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation.
Specimen part
View SamplesSkin and bladder epithelia form effective permeability barriers through the activation of distinct differentiation gene programs. Employing a genome-wide gene expression study, we identified transcription regulators whose expression correlates highly with that of differentiation markers both in bladder and skin, including the Grainyhead factor Get1/Grhl3, already known to be important for epidermal barrier formation. In the bladder, Get1 is most highly expressed in the differentiated umbrella cells and its mutation in mice leads to a defective bladder epithelial barrier formation due to failure of apical membrane specialization. Genes encoding components of the specialized urothelial membrane, the uroplakins, were downregulated in Get1-/- mice. At least one of these genes, Uroplakin II, is a direct target of Get1. The urothelial-specific activation of the Uroplakin II gene is due to selective binding of Get1 to the Uroplakin II promoter in urothelial cells, most likely regulated by histone modifications. These results demonstrate a key role for Get1 in urothelial differentiation and barrier formation.
The epidermal differentiation-associated Grainyhead gene Get1/Grhl3 also regulates urothelial differentiation.
Specimen part
View SamplesThe expansion, trafficking and functional effectiveness of adoptively transferred CD8+ T-cells play a critical role in mediating effective anti-tumor immunity. However, the mechanisms which program the highly proliferative and functional state of CD8+ T-cells are not completely understood. We hypothesized that IL-12, a cytokine commonly induced by TLR activation, could enhance T-cell priming by altering responsiveness to antigen and cytokines. Priming of tumor specific CD8+ T-cells in the presence of IL-12 induced the acquisition of a 'polyfunctional' effector response and increased the generation of memory cells. Moreover, IL-12 priming also promoted high levels of the IL-2 receptor alpha-chain (CD25) and robust IL-2 mediated activation of STAT5. This sensitivity to IL-2 translated into enhanced in vivo proliferation of adoptively transferred CD8+ T-cells. Furthermore, real-time, in vivo imaging of T-cell trafficking confirmed the ability of IL-12 priming to drive in vivo proliferation. IL-12 priming enhanced the anti-tumor function of adoptively transferred cells by reducing established subcutaneous tumor burden, and significantly increasing survival in an established intracranial tumor model. Finally, IL-12 priming of human PBMCs generates tumor specific T-cells phenotypically and functionally similar to IL-12 primed Pmel-1 T-cells. These results highlight IL-12 as an important mediator of CD8+ T-cell effector function and anti-tumor immunity.
Enhanced sensitivity to IL-2 signaling regulates the clinical responsiveness of IL-12-primed CD8(+) T cells in a melanoma model.
Sex, Specimen part, Treatment
View SamplesTranscriptional profile of PCSC spheres in SCM-1% KO (stem-like cells) vs adherent cultures in PCSC-Celprogen medium (differentiated-like cells)
Genomic profiling of tumor initiating prostatospheres.
Specimen part, Cell line
View SamplesBackground: MicroRNAs (miRNAs) are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. As such, they are believed to play a role in regulating the step-wise changes in gene expression patterns that occur during cell fate specification of multipotent stem cells. Here, we have studied whether terminal differentiation of C2C12 myoblasts is indeed controlled by lineage-specific changes in miRNA expression.
MicroRNA miR-378 promotes BMP2-induced osteogenic differentiation of mesenchymal progenitor cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Feasibility of developing reliable gene expression modules from FFPE derived RNA profiled on Affymetrix arrays.
Specimen part
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