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SRP158103
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
Long-lived quiescent mammary stem cells (MaSCs) are presumed to coordinate the dramatic expansion of ductal epithelium that occurs through the different phases of postnatal development, but little is known about the molecular regulators that underpin the activation of MaSCs. Here we show that ablation of the transcription factor Foxp1 in the mammary gland profoundly impairs ductal morphogenesis, resulting in a rudimentary tree throughout adult life. Foxp1-deficient glands were highly enriched for quiescent Tspan8hi MaSCs, which failed to become activated, even in competitive transplantation assays, and therefore harbor a cell-intrinsic defect. Luminal cells aberrantly expressed basal genes, suggesting that Foxp1 may also contribute to cell-fate decisions. Notably, Foxp1 was uncovered as a direct repressor of the Tspan8 gene in basal cells and deletion of Tspan8 could rescue the profound defects in ductal morphogenesis elicited by Foxp1 loss. Thus, a single transcriptional regulator, Foxp1, can control the exit of MaSCs from dormancy to orchestrate differentiation and development. Overall design: Basal and luminal epithelial cells were extracted from the mammary glands of floxed Foxp1 control and Foxp1 mammary gland conditional knockout mice. mRNA from three biological replicates of each cell population was profiled by RNA sequencing. All mice were female.
Publication Title
Foxp1 Is Indispensable for Ductal Morphogenesis and Controls the Exit of Mammary Stem Cells from Quiescence.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 63 Downloadable Samples
- NextSeq 500
Description
Background and aims: Hepatitis C virus (HCV) infection is a major cause of liver disease including steatosis, fibrosis and liver cancer. Viral cure cannot fully eliminate the risk of disease progression and hepatocellular carcinoma (HCC) in advanced liver disease. The mechanisms for establishment of infection, liver disease progression and hepatocarcinogenesis are only partially understood. To address these questions, we probed the functional proteogenomic architecture of HCV infection within a hepatocyte-model. Methods: Time-resolved HCV infection of hepatocyte-like cells was analyzed by RNA sequencing, proteomics, metabolomics, and leveraged by integrative genomic analyses. Using differential expression, gene set enrichment analyses, and protein-protein interaction mapping we identified pathways relevant for liver disease pathogenesis that we validated in livers of 216 cirrhotic patients with HCV. Results: We uncovered marked changes in the protein expression of gene sets involved in innate immunity, metabolism and hepatocarcinogenesis. In infected cells, HCV enhances glucose metabolism and creates a Warburg-like shift of the lactate flux. HCV infection impaired the formation of peroxisomes -organelles required for long-chain fatty acid oxidation- causing intracellular fatty acid accumulation, which is a hallmark of non-alcoholic fatty liver disease (NAFLD). Ex vivo studies confirmed perturbed peroxisomes and revealed an association of hepatic catalase expression with clinical outcomes and phenotypes in HCV-associated cirrhosis, NAFLD and HCC cohorts. Conclusion: Our integrative analyses uncover how HCV perturbs the hepatocyte cell circuits to drive chronic liver disease and hepatocarcinogenesis. This proteogenomic atlas of HCV infection provides a model for the discovery of novel drivers for viral- and non-viral induced liver disease. Overall design: mRNA profiles of either mock or HCV-infected Huh7.5.1dif cells, performed in triplicates and collected every day between days 0 and 10 post infection. HCV infection reached plateau at day 7 post infection (pi). After day 7 pi unspecific effects cannot be excluded.
Publication Title
Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus-Infected Cells and Liver to Identify Pathways Associated With Disease Development.
Sample Metadata Fields
Cell line, Subject
View Samples- Xenopus laevis
- 3 Downloadable Samples
Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
We implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.
Publication Title
Probing the Xenopus laevis inner ear transcriptome for biological function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Comparison of LAPC cells isolated from naive PBS treated and influenza treated mice.
Publication Title
Identification of a novel antigen-presenting cell population modulating antiinfluenza type 2 immunity.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Human peroxisome biogenesis disorders are lethal genetic disease in which abnormal peroxisome assembly compromises overall peroxisome and cellular function. Peroxisomes are ubiquitous membrane-bound organelles involved in several important biochemical processes, notably lipid metabolism and the use of reactive oxygen species for detoxification. Using cultured cells, we systematically characterized the peroxisome assembly phenotypes associated with dsRNA-mediated knockdown of 14 predicted Drosophila homologs of PEX genes (encoding peroxins; required for peroxisome assembly and linked to peroxisome biogenesis disorders), and confirmed that at least 13 of them are required for normal peroxisome assembly. We also demonstrate the relevance of Drosophila as a genetic model for the early developmental defects associated with the human peroxisome biogenesis disorders. Mutation of the PEX1 gene is the most common cause of peroxisome biogenesis disorders and is one of the causes of the most severe form of the disease, Zellweger syndrome. Inherited mutations in Drosophila Pex1 correlate with reproducible defects during early development. Notably, Pex1 mutant larvae exhibit abnormalities that are analogous to those exhibited by Zellweger syndrome patients, including developmental delay, poor feeding, severe structural abnormalities in the peripheral and central nervous systems, and early death. Finally, microarray analysis defined clusters of genes whose expression varied significantly between wild-type and mutant larvae, implicating peroxisomal function in neuronal development, innate immunity, lipid and protein metabolism, gamete formation, and meiosis.
Publication Title
A Drosophila model for the Zellweger spectrum of peroxisome biogenesis disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Previous studies identified a role for latent herpesvirus infection in cross-protection to infection and exacerbation of chronic inflammatory diseases. Here, we compared the gene expression signature from livers, spleens and brains of mice infected with wild-type gammaherpesvirus 68 (MHV68), a mutant virus defective in the establishment of latency (ORF73.stop) or mockulum. We identified over 600 genes differentially expressed in organs of mice latently infected with MHV68 and found distinct sets of genes linked to different pathways were altered in spleen compared to liver. Several of the most differentially expressed latency-specific genes (e.g. IFN, Cxcl9, Ccl5) are associated with known latency-specific phenotypes.
Publication Title
Latent gammaherpesvirus 68 infection induces distinct transcriptional changes in different organs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina Genome Analyzer
Description
MicroRNA (miRNA) and endogenous siRNA (endo-siRNA) are two essential classes of small noncoding RNAs (sncRNAs) in eukaryotic organisms. The class of miRNA is diverse and there exist noncanonical miRNAs that bypass the canonical miRNA biogenesis pathway. In order to identify noncanonical miRNAs and endo-siRNAs responding to virus infection and study their potential function, we sequenced small-RNA species from cells lytically infected with murine gammaherpesvirus 68. In addition to 3 novel canonical miRNAs in mouse, two antisense miRNAs in virus and 25 novel noncanonical miRNAs, including miRNAs derived from tRNAs, snoRNAs and introns, in the host were identified. These noncanonical miRNAs exhibited features distinct from canonical miRNAs in the lengths and structures of miRNA hairpins as well as base pairings and first nucleotide preference. Many of the novel miRNAs are conserved in mammals. In addition to several known murine endo-siRNAs detected by the sequencing profiling, a novel locus in the mouse genome was identified to give rise to endo-siRNAs. This novel endo-siRNA locus is comprised of two tandem inverted B4 short interspersed nuclear elements (SINEs). Unexpectedly, the SINE-derived endo-siRNAs were found in a variety of sequencing data as well as virus-infected cells. Moreover, a murine miRNA was up-regulated more than 35 fold in infected than in mock-treated cells. The putative target genes of the viral and the up-regulated murine miRNAs were potentially involved in processes of gene transcription and protein phosphorylation and localized to membranes, suggesting their role in manipulating the host basal immune system during lytic infection. Our results extended the number of noncanonical miRNAs in mammals and shed new lights on their potential functions of lytic infection of MHV68. Overall design: Mouse NIH 3T12 cells infectd with MHV68 (3 samples) and mock-treated (2 samples) were examined. Noncanonical microRNAs and endogenous siRNAs discovery in lytic infection of murine gammaherpesvirus MHV68 (NC_001826.2).
Publication Title
Identification of novel microRNA-like molecules generated from herpesvirus and host tRNA transcripts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cumulus cells surrounding mature oocytes that developed to moruale/blastocyst stage on day 5 of IVF cycle were collected and used for gene expression profiling using Affymetrix Human Gene 1.0 ST Arrays in order to determine differences in gene expression between the modified natural and stimulated in vitro fertilization (IVF) procedures.
Publication Title
Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Mouse strains have been identified that are resistant (i.e. DBA/2) or susceptible (i.e. C57BL/6) to infection from pathogenic fungus Coccidioides immitis. However, the genetic and immunological basis for this difference has not been fully characterized.
Publication Title
Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute to responses that protect mice from Coccidioides immitis infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 57 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Subcutaneous adipose tissue gene expression and DNA methylation respond to both short- and long-term weight loss.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples