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GSE68169
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A 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.
Publication Title
Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
Illumina HiSeq 2000
Description
Changes in gene expression caused by CREBBP/EP300 bromodomain inhibitors in a CML cell line Overall design: K562 cells were treated with CBP30 and I-CBP112 and changes in gene expression were evaluated by RNA-seq
Publication Title
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples SRP068961- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Antiprolifereative effects of CREBBP/EP300 inhibitors were tested in human leukemia and lymphoma cell lines and the molecular mechanisms responsible for such effects were explored. Overall design: K562 cells were treated with CBP-30 (CREBBP/EP300 bromodomain inhibitor), C646 (CREBBP/EP300 HAT activity inhibitor) and JQ1 (BRD4 inhibitor) and changes in gene expression were evaluated by RNA-seq.
Publication Title
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Considering the numerous complex and different pathological mechanisms involved in Alzheimers disease (AD) progression, treatments targeting a single cause may lead to limited benefits. The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.
Publication Title
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 20 Downloadable Samples
- IlluminaHiSeq2000
Description
Subclassification 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).
Publication Title
Cell of origin dictates aggression and stem cell number in acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 113 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NF-kappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Comparison of gene expression profiling analysis of bone marrow isolated CD34+ cells from patients with MALT lymphoma vs. healthy individuals revealed a large number of differentially expressed genes that included NF-kB target genes, genes involved in inflamatory signalling and immunoglobulin genes, suggesting an early lymphoid B-cell priming.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Attempts at modeling chromosomal translocations involving MALT1 gene, hallmarks of human mucosa-associated lymphoid tissue (MALT) lymphoma, have failed to reproduce the disease in mice. Here we describe a transgenic model in which MALT1 expression was targeted to mouse hematopoietic stem/progenitor cells. In Sca1-MALT1 mice, MALT1 deregulation activated the NF-kappaB pathway in Sca1+ cells, promoting selective B-cell differentiation and mature lymphocyte accumulation in extranodal tissues, progressively leading to the development of clonal B-cell lymphomas. These tumors recapitulated the histopathological features of human MALT lymphomas, presenting typical lymphoepithelial lesions and plasmacytic differentiation. Transcriptional profiling of Sca1-MALT1 murine lymphomas revealed overlapping molecular signatures with human MALT lymphomas, including MALT1-mediated NFkappaB activation, pro-inflammatory signaling and XBP1-induced plasmacytic differentiation. Moreover, murine Malt1 showed proteolytic activity by cleaving Bcl10 in Sca1-MALT1 lymphomas. Our novel technological approach has allowed modeling human MALT lymphoma in mice, which represent unique tools study MALT lymphoma biology and evaluate anti-MALT1 therapies.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The objective is to generate a robust and validated predictor profile for chemotherapy response in patients with mCRC using microarray gene expression profiles of primary colorectal cancer tissue.
Publication Title
Gene expression profile predictive of response to chemotherapy in metastatic colorectal cancer.
Sample Metadata Fields
Disease, Disease stage
View Samples