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SRP065840
Mus musculus
26 Downloadable Samples
Illumina HiSeq 2000
Description
RNA editing is a mutational mechanism that specifically alters the nucleotide content in sets of transcripts while leaving their cognate genomic blueprint intact. Editing has been detected from bulk RNA-seq data in thousands of distinct transcripts, but apparent editing rates can vary widely (from under 1% to almost 100%). These observed editing rates could result from approximately equal rates of editing within each individual cell in the bulk sample, or alternatively, editing estimates from a population of cells could reflect an average of distinct, biologically significant editing signatures that vary substantially between individual cells in the population. To distinguish between these two possibilities we have constructed a hierarchical Bayesian model which quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells and a cognate bulk sample consisting of ~ 106 cells. The model was applied to data from murine bone-marrow derived macrophages and dendritic cells, and predicted high variance for specific edited sites in both cell types tested. We then 1 validated these predictions using targeted amplification of specific editable transcripts from individual macrophages. Our data demonstrate substantial variance in editing signatures between single cells, supporting the notion that RNA editing generates diversity within cellular populations. Such editing-mediated RNA-level sequence diversity could contribute to the functional heterogeneity apparent in cells of the innate immune system. Overall design: 26 samples were subjected to RNA-seq: 24 single WT macrophages, and 2 bulk samples (Apobec1 WT and KO macrophages), consisting of 500,000-1 million cells each.
Publication Title
RNA editing generates cellular subsets with diverse sequence within populations.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple sclerosis involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system. Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells are stem cells in the central nervous system and the principal source of myelinating oligodendrocytes. These cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention. To discover therapeutic compounds for enhancing myelination from endogenous oligodendrocyte progenitor cells, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem-cell-derived oligodendrocyte progenitor cells. Here we show seven drugs function at nanomolar doses selectively to enhance the generation of mature oligodendrocytes from progenitor cells in vitro. Two drugs, miconazole and clobetasol, are effective in promoting precocious myelination in organotypic cerebellar slice cultures, and in vivo in early postnatal mouse pups. Systemic delivery of each of the two drugs significantly increases the number of new oligodendrocytes and enhances remyelination in a lysolecithin-induced mouse model of focal demyelination. Administering each of the two drugs at the peak of disease in an experimental autoimmune encephalomyelitis mouse model of chronic progressive multiple sclerosis results in striking reversal of disease severity. Immune response assays show that miconazole functions directly as a remyelinating drug with no effect on the immune system, whereas clobetasol is a potent immunosuppressant as well as a remyelinating agent. Mechanistic studies show that miconazole and clobetasol function in oligodendrocyte progenitor cells through mitogen-activated protein kinase and glucocorticoid receptor signalling, respectively. Furthermore, both drugs enhance the generation of human oligodendrocytes from human oligodendrocyte progenitor cells in vitro. Collectively, our results provide a rationale for testing miconazole and clobetasol, or structurally modified derivatives, to enhance remyelination in patients. Overall design: RNA sequencing of oligodendrocyte progenitor cells treated with vehicle, miconazole or clobetasol for 0, 2, 6, or 12 hours. Cells were plated 1.5 hours prior to addition of drug.
Publication Title
Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed. NRSF/REST is a transcriptional repressor that represses expression of neuronal genes in non-neural tissues. Some data suggest that SF-1 and NRSF/REST can functionally interact in adrenocortical cancer cells.
Publication Title
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Bos taurus
- 9 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Assessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress.
Publication Title
Deficiency in the α1 subunit of Na+/K+-ATPase enhances the anti-proliferative effect of high osmolality in nucleus pulposus intervertebral disc cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Our study describes in detail the role of Bmp2 during cardiac valve developmnent and its implication in Notch pathway activation. Overall design: Hearts were isolated from WT and Bmp2GOF;Nkx2.5-Cre mouse embryos at stage E9.5 and their expression profile characterized by RNA-seq
Publication Title
Bmp2 and Notch cooperate to pattern the embryonic endocardium.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
SF-1 is a nuclear receptor transcription factor playing a key role in adrenogonadal development and in adrenocortical tumorigenesis when overexpressed.
Publication Title
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Publication Title
Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
We analysed the combined effects of exposure to maternal diabetes and disrupted HIF-1 signaling on the transcriptom in cardiac left ventricles of 12 weeks old male mice. This approach provides the information about the long term changes originating in utero due to maternal diabetes and inefficient response to hypoxia which develops as a result of hyperglycemia. The majority of changes were detected in Hif1a insufficient mice exposed to maternal diabetes. Overall design: Streptozotocin induced diabetic FVB females were mated with non-diabetic males with global heterozygous deletion of Hif1a (Hif1a+/-). Total RNA was extracted from the LV of the hearts of 12-week-old male offspring in biological triplicates per each group (wt, non-diabetic pregnancy; wt, diabetic pregnancy; Hif1a+/-, non-diabetic pregnancy; Hif1a+/-, diabetic pregnancy). RNA profiles were generated by deep sequencing using Illumina NextSeq.
Publication Title
Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Bone marrow-derived macrophages were produced from mice lacking IL-10 alone (IL10-def) or mice lacking both IL-10 and the p50/p105 subunit of NF-kB (p50/IL10), and left unstimulated, stimulated with LPS (1 ng/ml) or stimulated with LPS and IL-10 (0.3 ng/ml).
Publication Title
NF-κB1 inhibits TLR-induced IFN-β production in macrophages through TPL-2-dependent ERK activation.
Sample Metadata Fields
Specimen part
View Samples