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SRP007827
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer II
Description
To gain insights into the interplay between DNA methylation and gene regulation we generated a basepair resolution reference map of the mouse methylome in stem cells and neurons. High genome coverage allowed for a novel quantitative analysis of local methylation states, which identified Low Methylated Regions (LMR) with an average methylation of 30%. These regions are evolutionary conserved, reside outside of CpG islands and distal to promoters. They represent regulatory regions evidenced by their DNaseI hypersensitivity and chromatin marks of enhancer elements. LMRs are occupied by transcription factors (TF) and their reduced methylation requires TF binding while introduction of TF binding sites creates LMRs de novo. This dependency on TF activity is further evident when comparing the methylomes of embryonic stem cells and derived neuronal cells. LMRs present in both cell types are occupied by broadly expressed factors, while LMRs present at only one state are occupied by cell-type specific TFs. Methylome data can thus enhance the prediction of occupied TF binding sites and identification of active regulatory regions genome-wide. Our study provides reference methylomes for the mouse at two cell states, identifies a novel and highly dynamic feature of the epigenome that defines distal regulatory elements and shows that transcription factor binding dynamically shapes mammalian methylomes. Overall design: Strand specific expression profiling by high throughput sequencing.
Publication Title
DNA-binding factors shape the mouse methylome at distal regulatory regions.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Type I Interferons encompasses a large family of closely related cytokines comprising of at least 13 IFN- isotypes and single IFN-. Both IFN- and IFN- exert their activity through a common receptor IFNAR. Type I Interferons have broad regulatory effects and various subtypes of dendritic cells are influenced by this cytokines. In our study we asked question whether the low, constitutive levels of type I Interferons produced under steady state conditions are important for proper function of splenic conventional dendritic cells.
Publication Title
Absence of IFN-beta impairs antigen presentation capacity of splenic dendritic cells via down-regulation of heat shock protein 70.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Biallelic defects of the gene encoding for the intracellular enzyme 3’ repair exonuclease (Trex)1 cause Aicardi-Goutières syndrome (AGS), a rare monogenic, lupus-like autoimmune disease, while heterozygous Trex1 loss of function alleles are associated with systemic lupus erythematosus (SLE). Trex1-/- mice develop lethal autoimmune multi-organ inflammation, which results from a chronic type I IFN response triggered by intracellular accumulation of a putative nucleic acid substrate of Trex1. This pathogenic nucleic acid is detected by the broadly, but not ubiquitously, expressed cytosolic DNA sensor cGAS, raising the question whether there are specific cell types that respond to Trex1 deficiency by production of IFN and induce autoimmunity. We generated mice with conditional knock out of the Trex1 gene and demonstrated that loss of Trex1 throughout the hematopoietic system and even selective loss in dendritic cells is sufficient to cause IFN release and autoimmunity. B cells showed no transcriptional response to Trex1 deficiency. Trex1-/- keratinocytes produced IFN but did not induce skin inflammation, whereas loss of Trex1 in cardiomyocytes triggered neither IFN response nor pathology. Trex1-deficient neurons and astrocytes did not release IFN in the CNS. In contrast, mice with selective inactivation of Trex1 in long-living CNS macrophages such as microglia locally produced IFN but did not reproduce the mild encephalitis seen in Trex1-/- mice. Collectively, individual cell types differentially respond to the loss of Trex1 and dendritic cells seem promising candidates for experiments addressing the molecular pathomechanism in Trex1 deficiency. Overall design: We sorted CD19-positive B cells from spleens of Trex1fl/fl CD19-Cre+ and Trex1fl/fl CD19-Cre- mice and isolated total RNA for library construction to perform mRNA deep sequencing.
Publication Title
Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 60 Downloadable Samples
- Illumina HiSeq 2000
Description
To elucidate responses of myeloid cells to SAMHD1 deficiency in the absence of exogenous viral infection, we performed global gene expression analysis of SAMHD1 deficient macrophages. Overall design: Peritoneal macrophages from 10 mutants and 10 controls were FACS sorted. Isolated RNA was subjected to next generation mRNA sequencing.
Publication Title
Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 2000
Description
To investigate the contribution of type-1 IFN signalling to the upregulation of IFN- stimulated genes in SAMHD1-deficient cells, we performed global gene expression analysis of SAMHD1-deficient IFNAR-/- macrophages. Overall design: Peritoneal macrophages from ten SAMHD1-deficient IFNAR-/- and six SAMHD1-deficient controls were FACS sorted. RNA was subjected to next generation mRNA sequencing.
Publication Title
Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
To elucidate responses of myeloid cells to SAMHD1 deficiency in the absence of exogenous viral infection, we performed global gene expression analysis of SAMHD1 deficient macrophages. Overall design: Peritoneal macrophages from nine mutants and nine controls were FACS sorted. Cells from three animals were pooled to yield three poolls per group. RNA from these pools was subjected to next generation mRNA sequencing
Publication Title
Mouse SAMHD1 has antiretroviral activity and suppresses a spontaneous cell-intrinsic antiviral response.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We compared the transcriptome in E16.5 embryonic mouse cortex isolated by microdissection, in control (+/+) mice and in mice with mutation in frizzled3 (Fzd3) and Celsr3. Overall design: Triplicate RNA samples prepared for each genotype
Publication Title
Feedback regulation of apical progenitor fate by immature neurons through Wnt7-Celsr3-Fzd3 signalling.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Polycomb protein group (PcG)-dependent trimethylation on H3-K27(H3K27me3) regulates identity of embryonic stem cells (SCs). How H3K27me3 governs adult SCs and tissue development is unclear. Here, we conditionally target H3-K27-methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin homeostasis. Postnatal phenotypes appear only in doubly-targeted skin, where H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, epidermis hyperproliferates and survives engraftment. mRNA-microarray studies reveal that despite these striking phenotypic differences, similar genes are upregulated in HF and epidermal Ezh1/2-null progenitors. Featured prominently are a) PcG-controlled non-skin lineage genes, whose expression is still significantly lower than in native tissues, and b) the PcG-regulated Ink4a/Inkb/Arf locus. Interestingly, even though Ink4a/Arf/Ink4b genes are fully activated in HF cells, they only partially so in epidermal-progenitors. Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing towards the relevance of this locus to the observed HF phenotypes. Our findings reveal new insights into Polycomb-dependent tissue control and provide a new twist to how different progenitors within one tissue respond to loss of H3K27me3.
Publication Title
EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). HFSCs regenerate hair in response to canonical Wnt signalling. We used RNA-seq to unfold genome-wide chromatin landscapes of ß-catenin within the native HFSC-niche. Overall design: ß-catenin control and cKO hair follicle stem cells (HFSCs) at the onset of anagen skins were FACS-purified for RNA-sequcencing. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing. Telogen>anagen activated bulge hair follicle stem cells (HFSCs) were FACS-purified for RNA-sequcencing.
Publication Title
In vivo transcriptional governance of hair follicle stem cells by canonical Wnt regulators.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Concurrent gene signatures for han chinese breast cancers.
Sample Metadata Fields
Specimen part
View Samples