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SRP070761
Mus musculus
5 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Purpose: Conditional knockout of Zfp36l1 Zfp36l2 in pro-B cells perturbs B cell development leading to reduced V(D)J recombination and diminished numbers of cells in successive stages of development. This RNA seq experiment aimed to determine the molecular pathways affected by loss of Zfp36l1 and Zfp36l2, and to deduce direct targets of these RNA binding proteins. Methods: RNAseq libraries were prepared from 0.1 µg of RNA from sorted control and DCKO late pre-B cells using TruSeq RNA sample preparation kit v2 modified to be strand specific using the dUTP method. Libraries were sequenced by an Illumina genome analyzer II measuring 54bp single-end reads. Over 30 million reads were measured from each sample. The reads were trimmed to remove adapter sequences using Trim Galore then mapped using Tophat (version 1.1.4) to the NCBIm37 mouse assembly (April 2007, strain C57BL/6J); reads with an identical sequence to more than one genomic locus were not mapped. Quality control analysis was carried out with FastQC. Results: Read counts for each gene were generated in SeqMonk: transcripts from the same gene were collapsed into a single transcript containing all exons, so total reads were counted without considering alternative splice forms. Since the libraries were strand-specific only reads on the opposing strand were counted. Differences in the abundance of transcripts between DCKO and control late pre-B cells were calculated in the R/Bioconductor program DESeq (version 1.12.1). Adjusted P values for differential expression were calculated in DESeq using a Benjamini-Hochberg correction: genes with an adjusted p-value of less than 5% were considered significant. Differentially expressed mouse transcripts identified using DESeq were analyzed for gene set enrichment using Toppfun. Conclusions: We identified an enrichment of mRNAs involved in cell cycle progression within Zfp36l1 Zfp36l2 double conditional knockouts. Overall design: RNAseq of late pre-B cells from control and Zfp36l1, Zfp36l2 double conditional knockout mice.
Publication Title
RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 113 Downloadable Samples
Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Homeodomain interacting protein kinase 2 (Hipk2) has previously been implicated in control of several transcription factors involved in embryonic development, apoptosis, cell proliferation and tumour development13. Analysis of gene expression in tissues from genetically heterogeneous mouse or human populations can reveal motifs associated with the structural or functional components of the tissue, and may predict roles for genes of unknown function4,5. Here we have applied this network strategy to uncover a novel role for the Hipk2 gene in the transcriptional system controlling adipogenesis. Both in vitro and in vivo models were used to show that knockdown or loss of Hipk2 specifically inhibits white adipose cell differentiation and tissue development. In addition, loss of Hipk2 leads to induction of pockets of multilocular brown fat-like cells in remaining white adipose depots. These cells express markers of brown and beige fat such as uncoupling protein 1 (Ucp1) and transmembrane protein 26 (Tmem26), and thermogenic genes including PPAR- coactivator 1a (Ppargc1a), and cell death-inducing DFFA-like effector a (Cidea). These changes are accompanied by increased insulin sensitivity in Hipk2 knock-out mice and reduced high fat diet-induced weight gain, highlighting a potential role for this kinase in diseases such as diabetes and obesity. Our study underscores the versatility and power of a readily available tissue, such as skin, for network modelling of systemic transcriptional programs involved in multiple pathways, including lipid metabolism and adipogenesis.
Publication Title
Identification of Hipk2 as an essential regulator of white fat development.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 1021 Downloadable Samples
- Illumina HiSeq 4000
Description
RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals in order to assess associated signatures Overall design: RNA-seq count data at 3 timepoints was generated for Zika-exposed and Zika-naïve individuals, extracted from PAXgene RNA blood solution with the PAXgene Blood RNA Kit using DNase digestion and an additional clean-up using RNEasy MinElute kit.
Publication Title
Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection.
Sample Metadata Fields
Sex, Age, Subject, Time
View Samples- Mus musculus, Mus musculus x mus spretus, Mus spretus
- 132 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility.
Sample Metadata Fields
Sex
View Samples- Mus musculus, Mus musculus x mus spretus, Mus spretus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression in self-renewing epithelial tissues is controlled by cis- and trans-activating regulatory factors that mediate responses to exogenous agents capable of causing tissue damage, infection, inflammation, or tumorigenesis. We used network construction methods to analyze the genetic architecture of gene expression in normal mouse skin in a cross between tumor-susceptible Mus musculus and tumor-resistant Mus spretus. We demonstrate that gene expression motifs representing different constituent cell types within the skin such as hair follicle cells, haematopoietic cells, and melanocytes are under separate genetic control. Motifs associated with inflammation, epidermal barrier function and proliferation are differentially regulated in mice susceptible or resistant to tumor development. The intestinal stem cell marker Lgr5 is identified as a candidate master regulator of hair follicle gene expression, and the Vitamin D receptor (Vdr) links epidermal barrier function, inflammation, and tumor susceptibility.
Publication Title
Genetic architecture of mouse skin inflammation and tumour susceptibility.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 68 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence.
Publication Title
Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Germline polymorphisms influence gene expression networks in normal mammalian tissues. Analysis of this genetic architecture can identify single genes and whole pathways that influence to complex traits including inflammation and cancer susceptibility. Changes in the genetic architecture during the development of benign and malignant tumours have not been investigated. Here, we document major changes in germline control of gene expression during skin tumour development as a consequence of cell selection, somatic genetic events, and changes in tumour microenvironment. Immune response genes such as Interleukin 18 and Granzyme E are under germline control in tumours but not in normal skin. Gene expression networks linked to tumour susceptibility and hair follicle stem cell markers in normal skin undergo significant reorganization during tumour progression. Our data highlight opposing roles of Interleukin-1 signaling networks in tumour susceptibility and tumour progression and have implications for the development of chemopreventive strategies to reduce cancer incidence.
Publication Title
Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in nave hosts.
Publication Title
Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
It was the purpose to analyse the changes in gene expression which occur in the mouse small intestine from the pre-weaning to the post-weaning stage. The gene expression was accordingly followed from postnatal day 4 to postnatal day 32.
Publication Title
Cellular cross talk in the small intestinal mucosa: postnatal lymphocytic immigration elicits a specific epithelial transcriptional response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 109 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Human tumours show a high level of clonal heterogeneity that contributes to malignant progression and metastasis, but the processes that influence the timing of metastatic dissemination of subclones are unknown. Here, we have used whole exome sequencing of 98 matched benign, malignant, and metastatic skin tumours from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumour, but then evolve separately, acquiring an additional set of mutations during growth at distant sites. Shared mutations between primary carcinomas and their matched metastases have the distinct A>T signature of the initiating carcinogen Dimethylbanzanthracene (DMBA), but non-shared mutations are primarily G>T or C>T substitutions, associated with oxidative stress. We found recurrent point mutations in several hundred genes, including several in the Ras (Hras, Kras, and Pik3ca) pathway. We propose that carcinogen-driven mouse tumour models can aid our understanding of the forces that shape clonal and genetic evolution of human cancers.
Publication Title
Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers.
Sample Metadata Fields
Sex
View Samples