Identify genes which are differentially expressed in ?Cop1ß compared to control islets and are also signficantly rescued in ?Cop1? ?ETV1/4/5ß Overall design: Islets were harvested from 5 biological replicates of the followig genotypes: Control, ?Cop1ß and ?Cop1? ?ETV1/4/5ß. Islets were individually handpicked and total RNA was isolated and purified for library preperation and Next Generation Sequencing.
β-Cell Insulin Secretion Requires the Ubiquitin Ligase COP1.
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View SamplesGene expression analysis of 7d-old Arabidopsis seedlings exposed to short term (2 h) hypoxia, long term (9 h) hypoxia, and 1 h reoxygenation after long term (9 h) hypoxia to evaluate the regulation of gene expression at the level of translation.
Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana.
Age
View SamplesEffects of hyperglycaemia and genetic background differences on renal gene expression
Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes.
Sex, Age, Specimen part, Disease, Subject
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Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Specimen part
View SamplesHdac3 is an important target of HDAC inhibitors used in the treatment of cutaneous T cell lymphoma. In order to gain an understanding of Hdac3 function in T cells,we deleted Hdac3 from early mouse thymocytes using LCK-Cre. Hdac3 deletion resulted in a loss of single positive thymocytes due to a defect in positive selection at the double positive (DP) stage of thymocyte development. To better characterize this defect, we sorted the DP1 and DP2 populations to for gene expression profiling. Overall design: Total RNA was extracted from DP1 (GFP+CD4+CD8+CD5loTCRblo) or DP2 (GFP+CD4+CD8+CD5hiTCRbint) thymocytes isolated by FACS from Hdac3+/+ or Hdac3F/F LCK-Cre+ animals. Libraries were constructed from rRNA-depleted total RNA pools to identify altered gene expression in DP populations following Hdac3 deletion.
Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Specimen part, Cell line, Subject
View SamplesAtherosclerosis is a transmural chronic inflammatory condition of small and large arteries that is associated with adaptive immune responses at all disease stages. However, impacts of adaptive immune reactions on clinically apparent atherosclerosis such as intima lesion (plaque) rupture, thrombosis, myocardial infarction, and aneurysm largely remain to be identified. It is increasingly recognized that leukocyte infiltrates in plaque, media, and adventitia are distinct but their specific roles have not been defined. To map these infiltrates, we employed laser capture microdissection (LCM) to isolate the three arterial wall laminae using apoE-/- mouse aorta as a model. RNA from LCM-separated tissues was extracted and large scale whole genome expression microarrays were prepared. We observed that the quality of the resulting gene expression maps was compromised by tissue RNA carried over from adjacent laminae during LCM. To account for these flaws, we established quality controls and algorithms to improve the predictive power of LCM-derived microarray data. Our approach creates robust transcriptome atlases of normal and atherosclerotic aorta. Assessing LCM transcriptomes for immunity-related mRNAs indicated markedly distinctive gene expression patterns in the three laminae of the atherosclerotic aorta. These mouse mRNA expression data banks can now be mined to address a wide range of questions in cardiovascular biology.
The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
Specimen part
View SamplesAdvances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 (Vanin 2) defines a distinct subpopulation of human fetal hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD90+CD38-GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in bone marrow stroma co-culture, and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSC migration between human fetal hematopoietic niches. The most highly enriched surface protein in GPI-80+ HSPC as compared to their progeny was Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of either GPI-80 or ITGAM was sufficient to perturb undifferentiated HSPC in stroma co-culture. These findings indicate that human fetal HSC utilize common mechanisms with leukocytes for cell-cell interactions governing HSC self-renewal.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
Specimen part
View SamplesAdvances in pluripotent stem cell and reprogramming technologies have given hope of generating hematopoietic stem cells (HSC) in culture. To succeed, greater understanding of the self-renewing HSC during human development is required. We discovered that glycophosphatidylinositol-anchored surface protein GPI-80 (Vanin 2) defines a distinct subpopulation of human fetal hematopoietic stem/progenitor cells (HSPC) with self-renewal ability. CD34+CD90+CD38-GPI-80+ HSPC were the sole population that maintained proliferative potential and undifferentiated state in bone marrow stroma co-culture, and engrafted in immunodeficient mice. GPI-80 expression also enabled tracking of HSC migration between human fetal hematopoietic niches. The most highly enriched surface protein in GPI-80+ HSPC as compared to their progeny was Integrin alpha-M (ITGAM), which in leukocytes cooperates with GPI-80 to support migration. Knockdown of either GPI-80 or ITGAM was sufficient to perturb undifferentiated HSPC in stroma co-culture. These findings indicate that human fetal HSC utilize common mechanisms with leukocytes for cell-cell interactions governing HSC self-renewal.
GPI-80 defines self-renewal ability in hematopoietic stem cells during human development.
Specimen part
View SamplesPheochromocytomas (PCC) are mostly benign tumors, amenable to complete surgical resection. However, 1017% of cases can become malignant, and once metastasized, there is no curative treatment for this disease. Given the need to identify effective therapeutic approaches for PCC, we evaluated the antitumor potential of the dual PI3K/mTOR inhibitor BEZ235 against these tumors. We employed an in vivo model of endogenous PCCs (MENX mutant rats), which closely recapitulate the human tumors. Mutant rats with PCCs were treated with 2 doses of BEZ235 (20 and 30 mg/kg), or with placebo, for 2 weeks. Treatment with BEZ235 induced cytostatic and cytotoxic effects on rat PCCs, which could be appreciated by both staining the tumors ex vivo with appropriate markers, and non-invasively by functional imaging (diffusion weighted-DW-MRI) in vivo.
Targeting PI3K/mTOR signaling exerts potent antitumor activity in pheochromocytoma in vivo.
Sex, Age, Specimen part, Treatment
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