Description

We differentiated mouse embryonic stem (mES) cells spontaneously into embryoid bodies (EBs). Gene expression of biological replicates of undifferentiated ES cells (0-day), 4-day, 8-day and 14-day EBs were measured by Affymetrix microarrays.

Publication Title

Modeling co-expression across species for complex traits: insights to the difference of human and mouse embryonic stem cells.

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No sample metadata fields

Description

The objectives of this study were to understand the effect of phenolic compounds from fermented berry beverages on hyperglycemia and obesity in vivo using mice fed a high fat diet. Our hypothesis was that consumption of a fermented blueberry-blackberry beverage and its phenolic compounds would reduce the development of obesity and hyperglycemia in diet-induced obese mice. Body composition, histomorphological analysis of pancreatic islets and liver, and expression of genes involved in obesity and hyperglycemia were evaluated in order to explain the modulation of diet-induced obesity and hyperglycemia due to treatments.

Publication Title

Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice.

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Sex, Age, Specimen part

Description

The rapid evolution of toxin resistance in animals has important consequences for the ecology of species and our economy. Pesticide resistance in insects has been a subject of intensive study, however, very little is known about how Drosophila species became resistant to natural toxins with ecological relevance, such as -amanitin that is produced in deadly poisonous mushrooms. Here we performed a microarray study to elucidate the genes, chromosomal loci, molecular functions, biological processes, and cellular components that contribute to the -amanitin resistance phenotype in Drosophila melanogaster. We suggest that toxin entry blockage through the cuticle, phase I and II detoxification, sequestration in lipid particles, and proteolytic cleavage of -amanitin contribute in concert to this quantitative trait. We speculate that the resistance to mushroom toxins in Drosophila melanogaster and perhaps in mycophagous Drosophila species has evolved as a cross-resistance to pesticides or other xenobiotic substances.

Publication Title

The mechanisms underlying α-amanitin resistance in Drosophila melanogaster: a microarray analysis.

Sample Metadata Fields

Specimen part

Description

Scope: Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here.

Publication Title

Isoflavones in soy flour diet have different effects on whole-genome expression patterns than purified isoflavone mix in human MCF-7 breast tumors in ovariectomized athymic nude mice.

Sample Metadata Fields

Cell line

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

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

Description

Acetylation of transcriptional regulators is normally dynamically regulated by nutrient status but is often persistently elevated in nutrient-excessive obesity conditions. We investigated the functional consequences of such aberrantly elevated acetylation of the nuclear receptor FXR as a model. Proteomic studies identified K217 as the FXR acetylation site in diet-induced obese mice. In vivo studies utilizing acetylation-mimic and -defective K217 mutants and gene expression profiling revealed that FXR acetylation increased proinflammatory gene expression, macrophage infiltration, and liver cytokine and triglyceride levels, impaired insulin signaling, and increased glucose intolerance. Mechanistically, acetylation of FXR blocked its interaction with the SUMO ligase PIASy and inhibited SUMO2 modification at K277, resulting in activation of inflammatory genes. SUMOylation of agonist-activated FXR increased its interaction with NF-B but blocked that with RXR, so that SUMO2-modified FXR was selectively recruited to and trans-repressed inflammatory genes without affecting FXR/RXR target genes. A dysregulated Acetyl/SUMO switch of FXR in obesity may serve as a general mechanism for diminished anti-inflammatory response of other transcriptional regulators and provide potential therapeutic and diagnostic targets for obesity-related metabolic disorders.

Publication Title

A dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity.

Sample Metadata Fields

Sex, Age, Specimen part

Description

One function of plant lectins is to serve as defenses against herbivorous insects. The midgut is the critical site affected by dietary lectins such as wheat germ agglutinin (WGA). We observed marked cellular structural and gene expression changes in Drosophila melanogaster third-instar larval midguts from insects WGA-fed or starved. Dietary WGA caused shortening, branching, swelling, distortion and in some cases disintegration of the midgut microvilli (Mv). Starvation was accompanied by shortening of the Mv. Microarray analyses revealed that dietary WGA evolved differential expression of 62 transcripts; seven of which were also differentially expressed in starved insects. The differentially regulated gene cluster in WGA-fed larvae were associated with (i) cytoskeletal organization, (ii) immune responses, (iii) detoxification reactions, and (iv) energy metabolism. Four putative transcription factor binding motifs (TFBMs) were associated with the differentially-expressed genes. At least one of these putative TFBMs exhibited substantial similarity to MyoD, a TFBM associated with cellular structures in mammals. These results are in keeping with the hypothesis that WGA causes a starvation-like effect as well as structural changes of midgut cells of Drosophila third-instar larvae.

Publication Title

No associated publication

Sample Metadata Fields

Specimen part

Description

The fidelity of sound transmission by cochlear implants in patients with sensorineural hearing loss could be greatly improved by increasing the number of frequency channels. This could be achieved by stimulating and guiding neurite outgrowth to reduce the distance between the implant's electrodes and the remnants of the spiral ganglion neurons. However, little is known about signaling pathways, besides those of neurotrophic factors, that are operational in the adult spiral ganglion. To systematically identify neuronal receptors for guidance cues in the adult cochlea, we conducted a genome-wide cDNA microarray screen with two-month-old CBA/CaJ mice. A meta-analysis of our data and those from older mice in two other studies revealed the presence of neuronal transmembrane receptors that represent all four established guidance pathwaysephrin, netrin, semaphorin, and slitin the mature cochlea as late as 15 months. In addition, we observed the expression of all known receptors for the Wnt morphogens, whose neuronal guidance function has only recently been recognized. In situ hybridizations located the mRNAs of the Wnt receptors frizzled 1, 4, 6, 9, and 10 specifically in adult spiral ganglion neurons. Finally, frizzled 9 protein was found in the growth cones of adult spiral ganglion neurons that were regenerating neurites in culture. We conclude from our results that adult spiral ganglion neurons are poised to respond to neurite damage, owing to the constitutive expression of a large and diverse collection of guidance receptors. Wnt signaling, in particular, emerges as a candidate pathway for guiding neurite outgrowth towards a cochlear implant after sensorineural hearing loss.

Publication Title

Expression of Wnt receptors in adult spiral ganglion neurons: frizzled 9 localization at growth cones of regenerating neurites.

Sample Metadata Fields

Sex, Specimen part

Description

Publication Title

Increasing alpha 7 beta 1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression.

Sample Metadata Fields

No sample metadata fields