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GSE4926
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In the past decade, several transcription factors critical for pancreas development have been identified. Despite this success, many of the cell surface and extracellular factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor HNF6 specifically in the pancreatic endocrine cell lineage resulted in the disruption of islet morphogenesis, including dysfunctional endocrine cell sorting, increased islet size, and failure of islets to migrate away from the ductal epithelium. We exploited the dysmorphic islets in pdx1PBHnf6 animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal pancreas tissue from wild type and pdx1PBHnf6 animals. We report the identification of genes with an altered expression in HNF6 Tg animals and highlight factors with potential importance in islet morphogenesis.
Publication Title
Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Warfare has long been associated with traumatic brain injury (TBI) in militarized zones. Common forms of TBI can be caused by a physical insult to the head-brain or by the effects of a high velocity blast shock wave generated by the detonation of an explosive device. While both forms of trauma are distinctly different regarding the mechanism of trauma induction, there are striking similarities in the cognitive and emotional status of survivors. Presently, proven effective therapeutics for the treatment of either form of TBI are unavailable. To be able to develop efficacious therapies, studies involving animal models of physical- and blast-TBI are required to identify possible novel or existing medicines that may be of value in the management of clinical events. We examined indices of cognition and anxiety-like behavior and the hippocampal gene transcriptome of mice subjected to both forms of TBI. We identified common behavioral deficits and gene expression regulations, in addition to unique injury-specific forms of gene regulation. Molecular pathways presented a pattern similar to that seen in gene expression. Interestingly, pathways connected to Alzheimers disease displayed a markedly different form of regulation depending on the type of TBI. While these data highlight similarities in behavioral outcomes after trauma, the divergence in hippocampal transcriptome observed between models suggests that, at the molecular level, the TBIs are quite different. These models may provide tools to help define therapeutic approaches for the treatment of physical- and blast-TBIs. Based upon observations of increasing numbers of personnel displaying TBI related emotional and behavioral changes in militarized zones, the development of efficacious therapies will become a national if not a global priority.
Publication Title
Changes in mouse cognition and hippocampal gene expression observed in a mild physical- and blast-traumatic brain injury.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia and vascular remodeling, acting via the HHT target genes, endoglin and ALK1. This study sought to identify endothelial BMP9-regulated proteins that could affect the HHT phenotype. Gene ontology analysis of cDNA microarray data obtained following BMP9 treatment of primary human endothelial cells indicated regulation of chemokine, adhesion, and inflammation pathways.
Publication Title
BMP9 regulates endoglin-dependent chemokine responses in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Blast traumatic brain injury (B-TBI) affects military and civilian personnel. Presently there are no approved drugs for blast brain injury. Exendin-4, administered subcutaneously, was evaluated as a pre-treatment (48 hours) and post-injury treatment (2 hours) on neurodegeneration, behaviors and gene expressions in a murine open field model of blast injury. B-TBI induced neurodegeneration, changes in cognition and genes expressions linked to dementia disorders. Exendin-4, administered pre- or post-injury ameliorated B-TBI-induced neurodegeneration at 72 hours, memory deficits from days 7-14 and attenuated genes regulated by blast at day 14 post-injury. The present data suggest shared pathological processes between concussive and B-TBI, with endpoints amenable to beneficial therapeutic manipulation by exendin-4. B-TBI-induced dementia-related gene pathways and cognitive deficits in mice somewhat parallel epidemiological studies of Barnes and co-workers who identified a greater risk in US military veterans who experienced diverse TBIs, for dementia in later life.
Publication Title
Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimers disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury.
Publication Title
Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Arabidopsis thaliana
- 7 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Aims We aim to use transcriptome analysis to establish on a genome-wide scale the identity and regulatory clusters of genes that specify microgametogenesis from the haploid microspore to mature functional pollen in Arabidopsis. Background Pollen as the haploid male gametophyte plays a vital role in plant fertility and crop production through the ability to deliver the male gametes in fertilisation. Despite the obvious importance for plant fertility and crop production we have a very limited understanding of the regulatory mechanisms that have evolved to specify male gametophyte development and functions and less than 150 genes have been identified that are gametophytically expressed in the anther.The availability of functional genomic resources now provides the opportunity to undertake a comprehensive approach to describing cellular development in terms of the transcriptome. This approach is particularly powerful where the complete transcriptome of a single developing cell can be analysed. The male gametophyte is a uniquely accessible cell type for such studies, enabling RNA analysis from distinct purified cell populations during development.The proposed experiments are designed to support a current application (P19208, Twell) to investigate the gametophytic transcriptome and transcription factor networks. The results obtained will extend our knowledge of the contribution of haploid gene expression to anther development and will be used directly to extend BBSRC funded work (P15086, Wilson) to investigate the role and targets the MALE STERILE 1 gene (MS1). In particular the data will be used in collaboration to extract haploid gene expression from datasets of transcriptome analysis of staged flower buds of wild type (Ler) and ms1. This work will also complement BBSRC funded work on sporogenesis (G13338, Dickinson and Scott) and meiosis (G15941, Franklin and Jones) that are focussed on earlier steps in anther development. Biological material and methods. Isolated microspores and pollen at 4 different developmental stages will be analysed. We will isolate spores from developmentally staged buds of Ler grown under defined growth conditions. Buds from several batches of 100 plants will be rapidly sorted into 4 groups according to developmental age, uninucleate microspores (UM), bicellular pollen (BP) tricellular pollen (TP) and mature pollen. Spores will be released by gentle mechanical tissue disruption and purified by filtration and purification of spores. We are confident that our spore isolation procedures are rigorous since we could not detect even trace expression of highly abundant sporophytic transcripts such RbcS and Cab transcripts in microarray data from pollen RNA.
Publication Title
Transcriptome analysis of haploid male gametophyte development in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 28 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Effects of loss-of-function of AtMIKC* MADS-box genes on the mature Arabidopsis pollen transcriptome.
Publication Title
MADS-complexes regulate transcriptome dynamics during pollen maturation.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Following our initial transcriptomic analyses of the male gametophyte development (Honys and Twell, Genome Biol 5:R85, 2004), we identified several candidate genes for the function of transcriptional regulators of the male gametophyte development.
Publication Title
AtbZIP34 is required for Arabidopsis pollen wall patterning and the control of several metabolic pathways in developing pollen.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
NextSeq 500
Description
Microglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
Publication Title
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples