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Mus musculus
16 Downloadable Samples
Illumina HiSeq 4000
Description
The overall goal of this study was to clarify the role of MeCP2 in adult cognition. As one of the measures we analyzed gene expression changes associated with MeCP2 loss in the adult hippocampus. The analysis was performed in basal conditions and after exposure to a novel environment. We report gene expression data of mouse adult hippocampal tissue in which MeCP2 has been knockeddown in both conditions. Overall design: Hippocampal mRNA profiles of 3 months old mice after delivery of a control shRNA sequence or a MeCP2-specific shRNA sequence by RNA-seq. Profiles in basal conditions and after (30 minutes) exposure to a novel environment were obtained. Each condition is in quadriplicate.
Publication Title
Adult hippocampal MeCP2 preserves the genomic responsiveness to learning required for long-term memory formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples
GSE86309- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray based mRNA profiling was used to identify the mechanism of action for the small molecule VLX60.
Publication Title
Mechanistic characterization of a copper containing thiosemicarbazone with potent antitumor activity.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Dysregulated oncogenic serine/threonine kinases play a pathological role in diverse forms of malignancies, including multiple myeloma (MM), and thus represent potential therapeutic targets. Here, we evaluated the biological and functional role of p21-activated kinase 4 (PAK4), and its potential as a new target in MM for clinical applications. PAK4 promoted MM cell growth and survival via activation of MM survival signaling pathways, including the MEK-ERK pathway. Furthermore, treatment with orally bioavailable PAK4 allosteric modulator (KPT-9274) significantly impacted MM cell growth and survival in a large panel of MM cell lines and primary MM cells alone and in the presence of bone marrow microenvironment. Intriguingly, we have identified FGFR3 as a novel binding partner of PAK4 and observed significant activity of KPT-9274 against t(4;14)-positive MM cells. These data support PAK4 as an oncogene in myeloma, and provide the rationale for the clinical evaluation of PAK4 modulator in myeloma.
Publication Title
Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
While the existence of intestinal epithelial stem cells (IESCs) has been well established, their study has been limited due to the inability to isolate them. Previous work has utilized side population (SP) sorting of the murine small intestinal mucosa to isolate a viable fraction of cells enriched for putative IESCs. We have used microarray analyses to characterize the molecular features of this potential stem cell population.
Publication Title
Molecular properties of side population-sorted cells from mouse small intestine.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Chronic tendon injuries, also known as tendinopathy, are common among professional and recreational athletes. These injuries result in a significant amount of morbidity and health care expenditure and yet little is known about the molecular mechanism leading to tendinopathy. We have used histological evaluation and molecular profiling to determine the gene expression changes in 23 human patients undergoing surgical procedures for the treatment of chronic tendinopathy. Diseased tendons have altered extracellular matrix, fiber disorientation, increased cellular content and vasculature and the absence of inflammatory cells. Global gene expression profiling identified 1783 transcripts with significant different expression patterns in the diseased tendons. Global pathway analysis further suggests altered expression of extracellular matrix proteins and the lack of an appreciable inflammatory response. We have identified pathways and genes regulated in tendinopathy samples that will help contribute to the understanding of the disease towards the development of novel therapeutics.
Publication Title
Regulation of gene expression in human tendinopathy.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 4000
Description
Adipocytes arise from commitment and differentiation of adipose precursors in white adipose tissue (WAT). In studying adipogenesis, precursor markers, including Pref-1 and PDGFRa, are used to isolate precursors from stromal vascular fraction of WAT, but the relationship among the markers is not known. Here, we used Pref-1 promoter-rtTA system in mice for labeling Pref-1+ cells and for inducible inactivation of Pref-1 target, Sox9. We show requirement of Sox9 for maintenance of Pref-1+ proliferative, early precursors. Upon Sox9 inactivation, these Pref-1+ cells become PDGFRa+ cells that express early adipogenic markers. Thus, we show for the first time that Pref-1+ cells precede PDGFRa+ cells in the adipogenic pathway and that Sox9 inactivation is required for WAT growth and expansion. Furthermore, we show that, in maintaining early adipose precursors, Sox9 activates Meis1 which prevents adipogenic differentiation. Our study also demonstrates the Pref-1 promoter-rtTA system for inducible gene inactivation in early adipose precursor population. Overall design: RNA-Sequencing for differentially expressed genes (more than 2-fold) between GFP+ (Pref-1+) ingWAT SVF cells from floxed and Sox9 PreASKO mice (n=6 pooled).
Publication Title
Sox9-Meis1 Inactivation Is Required for Adipogenesis, Advancing Pref-1<sup>+</sup> to PDGFRα<sup>+</sup> Cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Sox9-Meis1 Inactivation Is Required for Adipogenesis, Advancing Pref-1<sup>+</sup> to PDGFRα<sup>+</sup> Cells.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Both the mechanism of action and the factors determining the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of hippocampal neurons via enhanced serotonergic signaling, but it is still unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neurogenic effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. The behavioral and neurogenic responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis is a determinant of antidepressant efficacy.
Publication Title
Genetic regulation of behavioral and neuronal responses to fluoxetine.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 27 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2500
Description
Trastuzumab (Herceptinâ„¢), a humanized monoclonal antibody targeting the extracellular domain of human epidermal growth factor receptor-2 (HER2), is one of the most successful examples of targeted therapies for HER2-positive breast cancer. However, drug resistance remains daunting challenges. New combinatorial regimen of CDK4/6 inhibitors plus trastuzumab is currently under active clinical investigations. In this study, we seek to prospectively model the in vivo response to CDK4/6 inhibitor Palbociclib (Pal) plus trastuzumab (Ab) using transgenic Her2/Neu mouse model in parallel with the current clinical trial scenario. We performed single cell RNA-seqencing (Drop-seq) to profile and compare tumor cells and infiltrated immune cells derived from control, Ab+Pal sensitive/residual (APS) and resistant/progressive (APR) tumors. We revealed that although Ab+Pal treatment enhanced antigen processing, presentation and interferon signaling on tumor cells, a distinct immunosuppressive immature myeloid cells (IMCs) infiltrated in the resistant tumor microenvironment to promote resistant phenotype. Based on single cell gene set enrichment analysis (profiling) guided drug screening, we identified and evaluated a combinatorial immunotherapy regimen. We found that combinatorial immunotherapy with receptor tyrosine kinase inhibitor Cabozantinib and immune checkpoint blockades overcome Ab+Pal resistance by inhibiting IMCs and enhancing anti-tumor immunity. Moreover, our rationally designed sequential combinatorial regimens enabled durable response and sustained controlling of the emergence of acquired resistance, thus significantly improved outcomes of rapidly evolving Her2/Neu positive breast cancers. Our results implicate that single-cell RNA sequencing profiling guided combinatorial immunotherapy as a strategy to mitigate the emergence of resistance and to achieve long-term therapeutic benefit merits clinical translation. Overall design: Drop-seq of tumor cells and tumor infiltrating immune cells derived from FVB/N MMTV-neu202Mul mice with different treatment/phenotypes (sensitive and resistant tumors).
Publication Title
Single-cell profiling guided combinatorial immunotherapy for fast-evolving CDK4/6 inhibitor-resistant HER2-positive breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These data are from the brains (amygdala and hippocampus) of mice originally derived from a cross between C57BL/6J and A/J inbred strains. We used short-term selection to produce outbred mouse lines with differences in contextual fear conditioning, which is a measure of fear learning. We selected for a total of 4 generations. Fear learning differed in the selected lines and this difference was stronger with each successive generation of selection. We identified several QTLs for the selection response, including a highly significant QTL at the tyr locus (p < 9.6(-10)). We used Affymetrix microarrays to identify many differentially expressed genes in the amygdala and hippocampus of mice from the final generation of selection. Amygdala and hippocampus samples were rapidly dissected out of experimentally nave mice from each selected line. Three samples were pooled and hybridized to each array. Experimentally nave mice were used because the behavior of the mice can be reliably a nticipated due to their lineage. Thus these gene expression differences are not due to the response to human handling, foot shock or fear-inducing conditioned stimuli. We have a second similar study that focuses on a different selected population that was based on C57BL/6J and DBA/2J mice (see GES4035).
Publication Title
Rapid selection response for contextual fear conditioning in a cross between C57BL/6J and A/J: behavioral, QTL and gene expression analysis.
Sample Metadata Fields
No sample metadata fields
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