In this dataset, we included expression data obtained from 30 resected human PDAC tumors, to examine what genes are differentially expressed in different cohorts that might lead to various outcomes
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.
Specimen part
View SamplesBone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor- (TNF-) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.
Sex, Specimen part, Race, Subject
View SamplesObjective: To determine the effects of age and topographic location on gene expression in human neural retina.
Effects of aging and anatomic location on gene expression in human retina.
Sex, Age
View SamplesCutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5-UTR (HNRNPUL1, CCDC77, PES1), and 3-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.
Whole-genome landscapes of major melanoma subtypes.
No sample metadata fields
View SamplesExpression levels of the RNA-binding protein Quaking (QKI) are low in monocytes of early, human atherosclerotic lesions, but abundant in macrophages of advanced plaques. Specific depletion of QKI protein impaired monocyte adhesion, migration, differentiation into macrophages, and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, revealed striking changes in QKI-dependent mRNA levels and splicing of RNA transcripts. Overall design: RNA-seq analysis of primary monocytes and macrophages from a QKI haploinsufficient patient and their (control) sibling.
Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that terahertz (THz) irradiation of mouse mesenchymal stem cells with a pulsed broadband (centered at 10 THz) source, or a single-frequency, 2.52 THz, (SF) laser source, both with weak average power (<1mW/cm2), results in specific heterogenic changes in gene expression. The insignificant differential expression of heat shock and stress related genes as well as our temperature measurements imply a non-thermal response. The microarray survey and RT-PCR experiments demonstrate that at different irradiation conditions distinct groups of genes are activated. Stem cells irradiated for 12 hours with the broadband THz source exhibit an accelerated differentiation toward adipose phenotype, while the 2-hour (broadband or SF) irradiation affects genes transcriptionally active in pluripotent stem cells. Phenotypic and gene expression differences suggest that the THz effect depends on irradiation parameters such as duration and type of THz source, and on the level of stem cell differentiation. Computer simulations of the core promoters of two pluripotency markers reveal association between gene upregulation and propensity for DNA breathing. We propose that THz radiation has potential for non-contact control of cellular gene expression.
Specificity and heterogeneity of terahertz radiation effect on gene expression in mouse mesenchymal stem cells.
Specimen part
View SamplesWe report that extended exposure to broad-spectrum terahertz radiation results in specific changes in cellular functions that are closely related to DNA-directed gene transcription. Our gene chip survey of gene expression shows that whereas 89% of the protein coding genes in mouse stem cells do not respond to the applied teraherz radiation, certain genes are activated, while other are repressed. RT-PCR experiments with selected gene probes corresponding to transcripts in the three groups of genes detail the gene specific effect. The response was not only gene specific but also irradiation conditions dependent. Our findings suggest that the applied terahertz irradiation accelerates cell differentiation toward adipose phenotype by activating the transcription factor peroxisome proliferator-activated receptor gamma (PPARG). Finally, our molecular dynamics computer simulations indicate that the local breathing dynamics of the PPARG promoter DNA coincides with the gene specific response to the THz radiation. We propose that THz radiation is a potential tool for cellular reprogramming.
Mammalian stem cells reprogramming in response to terahertz radiation.
Specimen part, Treatment
View Samples