Compare the behaviour of two populations of non-hematopoetic stem cells (MSC and MAPC) isolated from human bone marrow. The effect of culture conditions on the behaviour of MSC was also characterised by isolating MSC and then culturing the cells for 96h in MAPC growth conditions
Validation of COL11A1/procollagen 11A1 expression in TGF-β1-activated immortalised human mesenchymal cells and in stromal cells of human colon adenocarcinoma.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sex, Age, Specimen part
View SamplesMultiple myeloma (MM) remains incurable despite the introduction of novel agents and a relapsing course is observed in the majority of patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from 17 MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the lost of lesions present at diagnosis, and DNA losses were significantly more frequent at relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly impact the gene expression of these samples, provoking a particular deregulation of IL-8 pathway. On the contrary, no relevant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although different statistical approaches were used to uncover genes whose abnormal expression at relapse was regulated by DNA methylation, only two genes significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative methylation-expression correlation. A deeper analysis demonstrated that DNA methylation was involved in regulation of SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were not apparently preceded by alterations in corresponding DNA. Taken together, these results showed that genomic heterogeneity, both at the DNA and RNA level, is a hallmark of MM transition from diagnosis to relapse.
Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse.
Sex, Specimen part
View SamplesBackground: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sex, Age, Specimen part
View SamplesNeuromedin U (NMU), which is thought to contribute to putative metastasis processes in various tumor entities, was identified as being up-regulated in breast cancer. Therefore, we aimed to uncover the role of NMU in breast cancer subtypes deciphering for the first time NMU-driven signalling pathways and downstream targets.
Oncogenic features of neuromedin U in breast cancer are associated with NMUR2 expression involving crosstalk with members of the WNT signaling pathway.
Sex, Age, Specimen part, Cell line, Race
View SamplesSubclassification of lymphoid neoplasms is often based on the presumed cell of origin based on T and B progenitor gene expression and the effect of cell lineage on influencing functional characteristics such as aggression and self-renewal capacity is largely unknown, accounted for in part, by lack of experimental models to address these questions. Here, we have used transgenic zebrafish to create the first models of Myc-induced B-ALL and mixed phenotypic B/T-ALL, opening new avenues for studying the these leukemias in the zebrafish. Our work has utilized syngeneic strain zebrafish, limiting dilution cell transplantation, and the widely reported rag2-Myc transgenic model to provide new understanding of how strain differences can underlie leukemia onset in the zebrafish model. Even more importantly, our work now for the first time, has allowed assessment of cell lineage on dictating aggression and leukemia stem cell frequency independent of the underlying oncogenic driver. In total, our work uncoveres that T-ALLs are more aggressive and have higher numbers of leukemia stem cells when compared with B-ALL and mixed phenotypic ALL. Furthermore, analysis of our biphenotypic B/T-ALL suggests that B cell pathways lock cells in less aggressive and lower stem cell fates and are dominant in regulating these processes when T cell pathways are co-regulated within ALL cells. Overall design: The goal of our study is to determine the transcriptional profiles of high and low self-renewing capacity tumors. 20 samples total: 11 unique samples (9 samples with biological replicates), 6 high self-renewing tumors (>1% cells could initiate leukemia) and 5 low self-renewing tumors (<1% of cells could initiate leukemia).
Cell of origin dictates aggression and stem cell number in acute lymphoblastic leukemia.
No sample metadata fields
View SamplesA detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism.
Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.
Sex, Age, Specimen part
View SamplesThe weaning period consist of a critical postnatal window for structural and physiologic maturation of rat beta cells. To investigate transcriptome changes involved in the maturation of beta cells neighboring this period we performed microarray analysis in FACS beta cell enriched populations to detail the global programme of gene expression to identify its changes during this process.
Transcriptome landmarks of the functional maturity of rat beta-cells, from lactation to adulthood.
Sex
View SamplesHuman umbilical cord Whartons jelly stem cells (WHJSC) are gaining attention as a possible clinical source of mesenchymal stem cells for use in cell therapy and tissue engineering due to their high accessibility, expansion potential and plasticity. However, the cell viability changes that are associated to sequential cell passage of these cells are not known. In this analysis, we have identified the gene expression changes that are associated to cell passage in WHJSC.
Evaluation of the cell viability of human Wharton's jelly stem cells for use in cell therapy.
Specimen part
View SamplesWe used microarrays to investigate gene expression changes in tumor-bearing Pax5+/- mice
Infection Exposure is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of Pax5-Inherited Susceptibility.
Specimen part
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