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SRP174375
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
Sensory functions of the vagus nerve are critical for specific aware perceptions and for monitoring visceral functions in the cardio-pulmonary and gastrointestinal systems. Here we present a comprehensive identification, classification, and validation of the neuron types in the neural crest (jugular) and placode (nodose) derived vagal ganglia by single cell transcriptomic (scRNA-seq) analysis. Our results reveal major differences between neurons derived from different embryonic origins. Jugular neurons exhibit fundamental similarities to the somatosensory spinal neurons, including major types such as C-low threshold mechanoreceptors (C-LTMRs), A-LTMRs, Ad-nociceptors, cold-, and mechano-heat C-nociceptors. In contrast, the nodose ganglion contains 18 distinct types dedicated to surveying the physiological state of the internal body. Our results reveal a vast diversity of vagal neuron types including many previously unanticipated types as well as proposed types that are consistent with chemoreceptors, nutrient detectors, baroreceptors, and stretch and volume mechanoreceptors of the respiratory, gastrointestinal, and cardiovascular systems. Overall design: Single-cell RNA-seq from 1896 vagal ganglion cells derived from wild-type and Vglut2Cre-Tomato animals originating from four replicates and consisting of the neuronal and non-neuronal cells that make up the ganglionic tissue.
Publication Title
An Atlas of Vagal Sensory Neurons and Their Molecular Specialization.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 302 Downloadable Samples
- Illumina HiSeq 2000
Description
We explore the heterogeneity of mouse thoracic ganglia demonstrating the presence of an unexpected variety of cell-types and identify specialized populations of nipple- and pilo-erector muscle neurons. These neurons extend axonal projections and are born amongst other neurons during embryogenesis, but remain unspecialized until target organogenesis occurs postnatally. Target innervation and cell-type specification is coordinated by an intricate acquisition of unique combinations of growth factor receptors and the initiation of expression of concomitant ligands by the nascent erector muscles. Overall design: RNA-seq analysis of 298 single sympathetic neuronal cells from the mouse thoracic ganglion
Publication Title
Visceral motor neuron diversity delineates a cellular basis for nipple- and pilo-erection muscle control.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Danio rerio
- 24 Downloadable Samples
Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) is a high-production volume organophosphate flame retardant widely used within the United States. Within zebrafish, initiation of TDCIPP exposure at 0.75 h post-fertilization (hpf) results in genome-wide alterations in methylation during cleavage (2 hpf) as well as epiboly delay or arrest (at higher concentrations) during late-blastula and early-gastrula (4-6 hpf). To determine whether these TDCIPP-induced effects were associated with impacts on the transcriptome, embryos were exposed to vehicle (0.1% DMSO) or 2 M TDCIPP from 0.75 hpf to 6 hpf, and total RNA was extracted from triplicate embryo pools per treatment and hybridized onto duplicate Affymetrix Zebrafish Gene 1.0 ST Arrays per RNA sample. Based on transcriptome-wide profiling, TDCIPP resulted in a significant impact on biological pathways involved in dorsoventral patterning and bone morphogenetic protein (BMP) signaling. Consistent with pathway-level responses, TDCIPP exposure also resulted in strongly dorsalized embryos by 24 hpf a phenotype that mimicked the effects of dorsomorphin, a potent and selective BMP inhibitor. Moreover, the majority of dorsalized embryos were preceded by epiboly arrest at 6 hpf. Our microarray data also revealed that the expression of sizzled (szl) a gene encoding a secreted Frizzled-related protein that limits BMP signaling was significantly decreased by nearly 4-fold at 6 hpf. Therefore, we used a splice-blocking morpholino to test the hypothesis that knockdown of szl phenocopies TDCIPP-induced delays in epiboly progression. Interestingly, contrary to our hypothesis, injection of szl MOs did not affect epiboly progression but, similar to chordin (chd) morphants, resulted in mildly ventralized embryos by 24 hpf. Overall, our findings suggest that TDCIPP-induced epiboly delay may be independent of szl expression and function, and that TDCIPP-induced dorsalization may similar to dorsomorphin be due to interference with BMP signaling during early zebrafish.
Publication Title
Tris(1,3-dichloro-2-propyl) phosphate disrupts dorsoventral patterning in zebrafish embryos.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
HCN4 channels are the major HCN channel isoform expressed in the sinoatrial node (SAN) and play a key role in cardiac pacemaking. We have characterized the gene expression profile in the SAN of adult mice expressing cAMP-insensitive HCN4 channels (HCN4FEA mice) in comparison to WT mice.
Publication Title
cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
A tissue like buccal mucosa (from cheek swabs) would be an ideal sample material for rapid, easy collection for testing of biomarkers as an alternative to blood. A limited number of studies, primarily in the smoker/oral cancer literature, address this tissue's efficacy for quantitative PCR or microarray gene expression analysis. In this study both qPCR and microarray analyses were used to evaluate gene expression in buccal cells. An initial study comparing blood and buccal cells from the same individuals looked at relative amounts of four genes. The RNA isolated from buccal cells was degraded but was of sufficient quality to be used with RT-qPCR to detect expression of specific genes. Second, buccal cell RNA was used for microarray-based differential gene expression studies by comparing gene expression between smokers and nonsmokers. The isolation and amplification protocol allowed use of 150-fold less buccal cell RNA than had been reported previously with human microarrays. We report here the finding of a small number of significant gene expression differences between smokers and nonsmokers, using buccal cells as target material. Additionally, Gene Set Enrichment Analysis confirmed that these genes were changing expression in the same pattern as seen in an earlier buccal cell study performed by another group. Our results suggest that in spite of a high degree of RNA degradation, buccal cells from cheek mucosa could be used to detect differential gene expression between smokers and nonsmokers. However the RNA degradation, increase in sample variability and microarray failure rate show that buccal samples should be used with caution as source material in expression studies.
Publication Title
Examining smoking-induced differential gene expression changes in buccal mucosa.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 72 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Glucocorticoids (GC) and 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are steroid hormones with anti-inflammatory properties with enhanced effects when combined. We previously showed that transcriptional response to GCs was correlated with inter-individual and inter-ethnic cellular response. Here, we profiled cellular and transcriptional responses to 1,25(OH)2 D3 from the same donors. We studied cellular response to combined treatment with GCs and 1,25(OH)2 D3 in a subset of individuals least responsive to GCs. We found that combination treatment had significantly greater inhibition of proliferation than with either steroid hormone alone. Overlapping differentially expressed (DE) genes between the two hormones were enriched for adaptive and innate immune processes. Non-overlapping differentially expressed genes with 1,25(OH)2 D3 treatment were enriched for pathways involving the electron transport chain, while with GC treatment, non-overlapping genes were enriched for RNA-related processes. These results suggest that 1,25(OH)2 D3 enhances GC anti-inflammatory properties through a number of shared and non-shared transcriptionally-mediated pathways.
Publication Title
Comparison of cellular and transcriptional responses to 1,25-dihydroxyvitamin d3 and glucocorticoids in peripheral blood mononuclear cells.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we present results of our DNA microarray analysis of samples from a timecourse study of individuals given ethanol orally, and then evaluated by breathalyzer to monitor blood alcohol content (BAC). At five blood alcohol levels, T1-T5, blood was drawn such that the samples represented 0%, 0.04%, 0.08% BAC, and return to 0.04%, and 0.02% BAC. Microarray analysis showed that changes in gene expression could be detected across the time-course. We verified these expression changes by quantitative polymerase chain reaction (qPCR). Candidate target genes identified from the microarray analysis were clustered by expression change pattern, examined for shared functions and functional network membership. Five coordinately expressed groups were revealed and functional analysis showed shared transcription factor binding sites and functions for members of the clusters. These functions include protein synthesis and modification, expected for changes in gene expression, hematological and immune functions, expected for a blood sample, and pancreatic and hepatic function, expected as response to ethanol. The results provide a first look at changing gene expression patterns in blood during acute increase of ethanol concentration and its depletion due to metabolism or excretion and demonstrate that it is possible to detect significant changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study can be utilized as part of a workflow to identify target genes by timecourse changes in gene expression that may affect pilot performance.
Publication Title
Microarray characterization of gene expression changes in blood during acute ethanol exposure.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina Genome Analyzer II, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina Genome Analyzer II
Description
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The peroxisome proliferator-activated receptor co-activator 1 (PGC-1) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, e.g. by co-activating the estrogen-related receptor (ERR) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these two proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERR to DNA in skeletal muscle cell line with elevated PGC-1 and linked the DNA recruitment to global PGC-1 target gene regulation. We found that, surprisingly, ERR co-activation by PGC-1 is only observed in the minority of all PGC-1 recruitment sites. Nevertheless, a majority of PGC-1 target gene expression is dependent on ERR. Intriguingly, the interaction between these two proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat binding site configuration for ERR, and adjacent recruitment of the transcription factor SP1. These findings thus not only reveal an unprecedented insight into the regulatory network underlying muscle cell plasticity, but also strongly link the genomic context of DNA response elements to control transcription factor - co-regulator interactions.
Publication Title
The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.
Sample Metadata Fields
Specimen part
View Samples