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GSE16438
Mus musculus
23 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A deletion in the CMAH gene in humans occurred approximately 3.5 million years ago. This resulted in the inactivation of the CMP-Neu5Ac hydroxylase enzyme, and hence, in the specific deficiency in N-glycolylneuraminic acid (Neu5Gc), a form of sialic acid, in all modern humans. Although there is evidence that this molecular milestone in the origin of humans may have led to the evolution of human-specific pathogens, how deficiency in Neu5Gc might alter progression of non-infectious human diseases remains unanswered. Here, we have investigated cardiac and skeletal muscle gene expression changes in mdx mice, a model of Duchenne muscular dystrophy (DMD), that do or do not carry the human-like inactivating mutation in the mouse Cmah gene. We have evidence that Neu5Gc-deficiency in humans might explain some of the discrepancies in the disease phenotype between mdx mice and DMD patients.
Publication Title
A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
Illumina HiSeq 2000
Description
Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. To further understand the role for H3K4 methylation, we overexpressed Flag epitope-tagged SET1-G990E (a dominant hyperactive allele of SET1) in yeast using the constitutive ADH1 promoter (ADH1p). As a control, we also overexpressed Flag epitope-tagged wild type SET1 in yeast. Analysis of gene expression in set1-null, jhd2-null and wild type SET1 or hypeactive SET1-G990E overexpressing mutants together revealed that the transcriptional regulation at a sub-set of genes, inclduing those governing glycogen metabolism and ribosome biogenesis, is highly sensitive to any change (i.e., loss or gain) in H3K4 methylation levels. Overall, we find combined activities of Set1 and Jhd2 via dynamic modulation of H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Overall design: Gene expression changes were generated from five different yeast strains representing wild type control, set1 null and jhd2 null mutants, and wild type SET1 or dominant hyperacive SET1-G990E overexpressing mutants. Three independent biological samples were grown for each strain, total RNA was isolated, libraries were prepared, sequenced, and analyzed separately.
Publication Title
Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 126 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We hypothesize that germline variation influences susceptibility to aggressive prostate tumor
Publication Title
A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina HiSeq 1500
Description
Macrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and alterations in mRNA levels were analyzed. We identified three transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands, in the presence of three different “reprogramming” signals; high density immune complexes (IC), prostaglandin E2 (PGE2), or adenosine (Ado). All three of these cell populations produced higher levels of transcripts for IL-10, and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1Beta, IL-6, and IL-12. All three macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore we consider each to have immunoregulatory activity. This immunoregulatory activity occurred equally well in macrophages from stat6-deficient mice. The lack of STAT6 did not affect macrophages’ ability to reciprocally change cytokine production or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These immunoregulatory macrophages are transcriptionally and functionally related, and quite distinct from macrophages treated with IL-4.
Publication Title
The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 17 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
microRNAs play crucial roles in the early development of an organism. However the regulation of transcription through the action of microRNAs during the initial embyonic development has not been studied.
Publication Title
miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- NextSeq 500
Description
Use NGS-transcriptome profiling (RNA-seq) to investigate deregulated genes involved in the proliferative effects of ID-8 and Harmine after hypoxia-induced damage in primary human proximal tubular epithelial cells (HPTECs) Overall design: Examination of differentially expressed genes in HPTECs treated with 1uM of ID-8; or 1uM of Harmine; or EGF in comparison to cells without treatment after 24 hours of hypoxia, in triplicates
Publication Title
A High-Throughput Screen Identifies DYRK1A Inhibitor ID-8 that Stimulates Human Kidney Tubular Epithelial Cell Proliferation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Pressure overload-induced cardiac hypertrophy was examined in IL-18 knockout and littermate control mice.
Publication Title
Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells. Overall design: B cells derived from control and CD19-Cre;Id3loxP/loxP mice were activated in vitro in the presence of LPS and IL-4 for 24 or 48 hours. RNA was isolated from naïve as well as activated control and CD19-Cre;Id3loxP/loxP mice and analyzed by RNA-seq, in duiplicate.
Publication Title
Id3 Orchestrates Germinal Center B Cell Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 81 Downloadable Samples
- Illumina HiSeq 2500
Description
Agonistic encounters with conspecifics are powerful effectors of future behavior that evoke strong and durable neurobiological responses. We recently identified a deeply conserved “toolkit” of transcription factors (TFs) that respond to social challenge across diverse species in coordination with distinct conserved signatures of energy metabolism and developmental signaling. To further characterize this response and its transcriptional drivers in mice, we examined gene expression and chromatin landscape in the hypothalamus, frontal cortex, and amygdala of socially challenged and control animals over time. The data revealed a complex spatiotemporal pattern of metabolic, neural, and developmental transcriptomic signatures coordinated with significant shifts in the accessibility of distally located regulatory elements. Transcriptional regulatory network and motif analyses revealed an interacting network of TFs correlated with differential gene expression across the tissues and time points we assayed, including the early-acting and conserved regulator of energy metabolism and development, ESRRA. Cell-type deconvolution analysis attributed the early metabolic activity implicated by our transcriptomic analysis primarily to oligodendrocytes and the developmental signal to neurons, and we confirmed the presence of ESRRA in both oligodendrocytes and neurons throughout the brain. To assess the role of this nuclear receptor as an early trigger of this coordinated response, we used chromatin immunoprecipitation to map ESRRA binding sites to a set of genes involved in metabolic regulation and enriched in challenge-associated differentially expressed genes. Together, these data support a rich model linking metabolic and neural responses to social challenge, and identify regulatory drivers with unprecedented tissue and temporal resolution. Overall design: Territory-holding resident mice were males from the C57BL/6J strain co-housed with females to establish a territory. Intruder mice were males from the BALB/C strain. Animals were housed in a 12L:12D animal room until the resident-intruder paradigm was undertaken. Before behavior work, male C57BL/6J animals were cohoused with members of the same sex for two weeks, housed alone for a week, and then housed with a single C57BL/6J female for a week to establish a territory. Thus, before behavior work, the animals were allowed to habituate to our animal facility for four weeks. Three hours before testing, females were removed from the resident males’ cages. Immediately before the trial, residents’ cages were inserted into a blank-walled chamber. For experimental mice, we introduced unfamiliar intruder BALB/cJ male mice. Intruders were contained within a stainless steel wire ~1cm mesh cage to prevent animals from making contact and injuring one another. Control animals were exposed to the same cage, but containing a paper cup instead of an intruder mouse. The cages were removed in both intruder and control conditions after five minutes. After exposure to the intruder or control stimulus, resident animals were allowed to sit in a dark and quiet place for either 30 minutes, 60 minutes, or 120 minutes. Residents were then immediately euthanized by cervical dislocation. As soon as animals were euthanized, we extracted three brain regions of interest from our animals: frontal cortex, hypothalamus, and amygdala. This yielded tissue samples from which RNA was extracted. The RNA samples were pooled to generate libraries for sequencing. For control mice there were 5 replicates for all combinations of time after stimulus (30, 60, 120 minutes) and brain region (frontal cortex, hypothalamus, amygdala) except for hypothalamus from control mice after 30 minutes (3 replicates) and for frontal cortex from control mice after 120 minutes (6 replicates). For experimental mice there were 5 replicates for all combinations of time after stimulus (30, 60, 120 minutes) and brain region (frontal cortex, hypothalamus, amygdala) except for frontal cortex from experimental mice after 120 minutes (6 replicates).
Publication Title
Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Deletion of Hdac3 impaired DNA repair and greatly reduced chromatin compaction and heterochromatin content. Liver-specific deletion of Hdac3 culminated in hepatocellular carcinoma. The loss of genomic stability and the impaired response to DNA damage suggested that a high mutation rate stimulated the development of HCC. To begin to assess what pathways were involved in the formation of HCC, we performed gene expression analysis using cDNA microarrys.
Publication Title
Hdac3 is essential for the maintenance of chromatin structure and genome stability.
Sample Metadata Fields
Specimen part
View Samples