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SRP155937
Homo sapiens
12 Downloadable Samples
Illumina HiSeq 2500
Description
Purpose: The goals of this study are to compare the effects of 5% and 20% oxygen culture on human embryonic stem cells, inlcuding the impact on their transcriptomes. Overall design: mRNA profiles of two human embryonic stem cell lines (MEL1 and MEL2) cultured long term at 5% and 20% oxygen.
Publication Title
Oxygen Regulates Human Pluripotent Stem Cell Metabolic Flux.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Nuclear receptor subfamily 1, group D, member 1 (Nr1d1) (also known as Rev-erb alpha) has been linked to circadian rhythm regulation, mood-related behavior, and disorders associated with social deficits. Recent work from our laboratory found striking decreases in Nr1d1 in nucleus accumbens (NAc) in the maternal condition and indirect evidence that Nr1d1 was interacting with numerous addiction and reward-related genes to modulate social reward. In this study, we applied our insights from the maternal state to non-parental adult mice to determine whether decreases in Nr1d1 expression in NAc via adeno-associated viral (AAV) vectors and short hairpin RNA (shRNA)-mediated gene knockdown were sufficient to modulate social reward and mood-related behaviors. We also used microarray analysis of to identify gene expression alterations induced by the lowering of Nr1d1 expression.
Publication Title
The circadian gene Nr1d1 in the mouse nucleus accumbens modulates sociability and anxiety-related behavior.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bipolar disorder (BPD) is a debilitating heritable psychiatric disorder. Contemporary models for the manic pole of BPD have primarily utilized either single locus transgenics or treatment with psychostimulants. Our lab recently characterized a mouse strain, termed Madison (MSN), which naturally displays a manic phenotype, exhibiting elevated locomotor activity, increased sexual behavior, and higher forced swimming relative to control strains. Lithium chloride and olanzapine treatments attenuate this phenotype. In this study, we replicated our locomotor activity experiment, showing that MSN mice display generationally-stable mania relative to their outbred ancestral strain, hsd:ICR (ICR). We then performed a gene expression microarray experiment to compare hippocampus of MSN and ICR mice. We found dysregulation of multiple transcripts whose human orthologs are associated with BPD and other psychiatric disorders including schizophrenia and ADHD, including: Epor, Smarca4, Cmklr1, Cat, Tac1, Npsr1, Fhit, and P2rx7. RT-qPCR confirmed dysregulation for all of seven transcripts tested. Using a network analysis, we found dysregulation of a gene system related to chromatin packaging, a result convergent with recent human findings on BPD. Using a novel genomic enrichment algorithm, we found enrichment in genome regions homologous to human loci implicated in BPD in replicated linkage studies including homologs of human cytobands 1p36, 3p14, 3q29, 6p21-22, 12q24, 16q24, and 17q25. Our findings suggest that MSN mice represent a polygenic model for the manic pole of BPD showing much of the genetic systems complexity of the corresponding human disorder. Further, the high degree of convergence between our findings and the human literature on BPD brings up novel questions about evolution by analogy in mammalian genomes.
Publication Title
A new mouse model for mania shares genetic correlates with human bipolar disorder.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in 5 of 5 independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder, and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions.
Publication Title
Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The transition from the non-maternal to the maternal state is characterized by a variety of CNS alterations that support the care of offspring. The septum (including lateral and medial portions) is a brain region previously linked to various emotional and motivational processes, including maternal care. In this study, we used microarrays (PLIER algorithm) to examine gene expression changes in the septum of postpartum mice and employed gene set enrichment analysis (GSEA) to identify possible regulators of altered gene expression. Genes of interest identified as differentially regulated with microarray analysis were validated with quantitative real-time PCR. We found that fatty acid binding protein 7 (Fabp7) and galanin (Gal) were downregulated, whereas insulin-like growth factor binding protein 3 (Igfbp3) was upregulated in postpartum mice compared to virgin females. These genes were previously found to be differentially regulated in other brain regions during lactation. We also identified altered expression of novel genes not previously linked to maternal behavior, but that could play a role in postpartum processes, including glutamate-ammonia ligase (Glul) and somatostatin receptor 1 (Sstr1) (both upregulated in postpartum). Genes implicated in metabolism, cell differentiation, or proliferation also exhibited altered expression. Unexpectedly, enrichment analysis revealed a high number of microRNAs, transcription factors, or conserved binding sites (177 with corrected P-value <0.05) that were significantly linked to maternal upregulated genes, while none were linked to downregulated genes. MicroRNAs have been linked to placenta and mammary gland development, but this is the first indication they may also play a key role in sculpting the maternal brain. Together, this study provides new insights into genes (along with possible mechanisms for their regulation) that are involved in septum-mediated adaptations during the postpartum period.
Publication Title
Gene expression changes in the septum: possible implications for microRNAs in sculpting the maternal brain.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Coordinated gene expression changes across the CNS help to produce the mammalian maternal phenotype. Lateral septum (LS) is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum) in selectively bred maternal mice. Here, we expand on the prior study by 1) conducting microarray analysis solely on LS in virgin and postpartum mice, 2) using outbred mice, and 3) evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including nine GABAA receptor subunits (p<0.05). Subunits 4 and were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive 4/ containing receptor subtype. Conversely, subunits and were increased in maternal LS. Sixteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated), hypocretin receptor 1 (Hcrtr1), kappa opioid receptor 1 (Oprk1), and transient receptor potential channel 4 (Trpc4). Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C) motif ligand 12 (Cxcl12), fatty acid binding protein 7 (Fabp7), plasma membrane proteolipid (Pllp), and suppressor of cytokine signaling 2 (Socs2). Additional genes that are linked to anxiety, such as glutathione reductase (Gsr), exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.
Publication Title
Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
We describe a method for isolating RNA suitable for high-throughput RNA sequencing (RNA-seq) from small numbers of fluorescently labeled cells isolated from live zebrafish (Danio rerio) embryos without using costly, commercially available columns. This method ensures high cell viability after dissociation and suspension of cells and gives a very high yield of intact RNA. We demonstrate the utility of our new protocol by isolating RNA from fluorescence activated cell sorted (FAC sorted) pineal complex neurons in wild-type and tbx2b knockdown embryos at 24 hours post fertilization. Tbx2b is a transcription factor required for pineal complex formation. We describe a bioinformatics pipeline used to analyze differential expression following high-throughput sequencing and demonstrate the validity of our results using in situ hybridization of differentially expressed transcripts. This protocol brings modern transcriptome analysis to the study of small cell populations in zebrafish. Overall design: Differential expression analysis of mRNA levels in a single time-point (24 hpf) between wild-type and Tbx2b deficient FAC sorted pineal complex cells
Publication Title
Identification of differentially expressed genes during development of the zebrafish pineal complex using RNA sequencing.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 5 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Alterations in the composition of the gut microbiome have an emerging role in brain function and behaviour. We have porposed that short chain fatty acids (SCFA) including propionate and butyrate which are present in the diet and are fermantation products of many gastrointestinal bacteria are contributing environmental factors in autism spectrum disorders (ASD). Here we used the microarray technology to compare global changes in gene expression profiles following exposure of PC12 cells to structurally related SCFA propionate and butyrate each in two different concentrations. Large number of affected genes, common for both SCFA were identified, including genetic networks and GO processes implicated in ASD.
Publication Title
Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells--possible relevance to autism spectrum disorders.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In order to gain further insight into the molecular mechanism(s) mediating the blunted epinephrine responses following recurrent hypoglycemia we utilized global gene expression profiling approach. Our results indicate the association between defective counterregulation (impaired epinephrine release) and the activation of the unfolded protein response as well as increased neuropeptide signaling, altered ion homeostasis and downregulation of proteins involved in Ca2+-dependent exocytosis of secretory vesicles.
Publication Title
Whole genome expression profiling associates activation of unfolded protein response with impaired production and release of epinephrine after recurrent hypoglycemia.
Sample Metadata Fields
Specimen part, Time
View Samples- Arabidopsis thaliana
- 28 Downloadable Samples
- Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
We analysed the translatome and transcriptome of Arabidopsis thaliana Col-0 WT at five distinct physiological states during seed germination.
Publication Title
Extensive translational regulation during seed germination revealed by polysomal profiling.
Sample Metadata Fields
Specimen part, Time
View Samples