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SRP099191
Mus musculus
57 Downloadable Samples
Illumina HiSeq 2500
Description
We tested the gene expression difference between PDGFRa+ fibroblasts FACS sorted from nulliparous balb/c mouse mammary glands and 6 days post-weaning mammary glands Overall design: 2 biological replicates of fibroblasts from nulliparous mammary glands and 3 biological replicates of fibroblasts from 6 days post-weaning mammary glands were used for comparison.
Publication Title
Physiologically activated mammary fibroblasts promote postpartum mammary cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 104 Downloadable Samples
- Illumina HiSeq 2000
Description
Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction. Overall design: Endothelium from hypertensive mice were acutely extracted at two different ages (4 weeks and 22 weeks) and compared to endothelium from 22 week old normotensive mice.
Publication Title
Endothelial transcriptomics reveals activation of fibrosis-related pathways in hypertension.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease whose predominant neuropathological signature is the selective loss of medium spiny neurons in the striatum. Despite this selective neuropathology, the mutant protein (huntingtin) is found in virtually every cell so far studied, and, consequently, phenotypes are observed in a wide range of organ systems both inside and outside the central nervous system. We, and others, have suggested that peripheral dysfunction could contribute to the rate of progression of striatal phenotypes of HD. To test this hypothesis, we lowered levels of huntingtin by treating mice with antisense oligonucleotides (ASOs) targeting the murine Huntingtin gene. To study the relationship between peripheral huntingtin levels and striatal HD phenotypes, we utilized a knock-in model of the human HD mutation (the B6.HttQ111/+ mouse). We treated mice with ASOs from 2-10 months of age, a time period over which significant HD-relevant signs progressively develop in the brains of HttQ111/+ mice. Peripheral treatment with ASOs led to persistent reduction of huntingtin protein in peripheral organs, including liver (64% knockdown), brown adipose (66% knockdown), and white adipose tissues (71% knockdown). This reduction was not associated with alterations in the severity of HD-relevant signs in the striatum of HttQ111/+ mice at the end of the study, including transcriptional dysregulation, the accumulation of neuronal intranuclear inclusions, and behavioral changes such as subtle hypoactivity and reduced exploratory drive. These results suggest that the amount of peripheral reduction achieved in the current study does not significantly impact the progression of HD-relevant signs in the central nervous system. Overall design: HttQ111/+ and Htt+/+ mice were given weekly intraperitoneal injections of Htt ASO, control ASO, or saline from 2 to 10 months of age. Striatal mRNA was sequenced from and N of 5-6 per arm (N=35 total).
Publication Title
Peripheral huntingtin silencing does not ameliorate central signs of disease in the B6.HttQ111/+ mouse model of Huntington's disease.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We examined global gene expression patterns in response to PGC-1 expression in cells derived from liver or muscle.
Publication Title
Direct link between metabolic regulation and the heat-shock response through the transcriptional regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood.
Publication Title
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1 down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1 on expression of genes encoding secreted proteins. Interestingly, PGC-1 requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1 modulates the secretome of mouse embryonic fibroblasts (MEFs).
Publication Title
Control of Secreted Protein Gene Expression and the Mammalian Secretome by the Metabolic Regulator PGC-1α.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
The inhibitor of DNA binding 2 (Id2) is essential for NK cell development with its canonical role in this pathway being to antagonize E-proteins, silencing E-box gene expression and subsequent commitment to the T and B cell lineages. However, how E-box genes prevent NK cell development and homeostasis remains enigmatic. Here we identify a key role for Id2 in regulating the threshold for IL-15 receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Deletion of Id2 in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling. Id2-null NK cells displayed impaired IL-15 mediated JAK1/STAT5 phosphorylation, compromised metabolic function and enhanced apoptosis. Remarkably, Id2-null NK cell homeostasis could be fully rescued in vivo by IL-15 receptor stimulation and partially rescued by genetic ablation of Socs3. During normal NK cell maturation we observed an inverse correlation between the expression levels of E-protein target genes and Id2. These results shift the current paradigm on the role of Id2, indicating that it is not only required to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Overall design: Transcriptional profiling of wild type and Id2-null natural killer (NK) cells using RNA sequencing
Publication Title
The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Rattus norvegicus
- 38 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The expression levels of many genes show wide natural variation among strains or populations. This study investigated the potential for animal strain-related genotypic differences to confound gene expression profiles in acute cellular rejection (ACR). Additional analysis allowed for selection of 49 candidate genes uniquely associated with ACR, but only after accounting for the unexpectedly large effect of animal strain. Studies of ACR that examine gene expression in peripheral blood may be confounded by strain differences. These results indicate the need for study designs that eliminate or control for the large effect of genetic background on the transcriptome of immune cells.
Publication Title
Impact of animal strain on gene expression in a rat model of acute cardiac rejection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
- IlluminaHiSeq2500
Description
Tissue-resident memory T cells (Trm) are non-circulating memory T cells that localize to portals of pathogen entry such as the skin, gut and lung where they provide efficient early protection against reinfection. Trm are characterized by a molecular profile that actively prevents egress from peripheral sites including the constitutive expression of the lectin CD69 and down-regulation of the chemokine receptor (CCR)7 and sphingosine-1-phosphate receptor 1 (S1PR1). This program is partially mediated by down-regulation of the transcription factor KLF2; however, to date no transcriptional regulator specific to Trm has been identified. Here we show that the Blimp1 related transcription factor Hobit is specifically upregulated in Trm and together with Blimp1, mediates the development and maintenance of Trm in various tissues including skin, gut, liver and kidney. Importantly, we found that the Hobit/Blimp1 transcriptional module is also required for other tissue-resident lymphocytes including Natural Killer T (NKT) cells and liver tissue-resident NK cells (trNK). We show that these populations share a universal transcriptional program with Trm instructed by Hobit and Blimp1 that includes the repression of CCR7, S1PR1 and KLF2 thereby enforcing tissue retention. Our results identify Hobit and Blimp1 as major common regulators that drive the differentiation of distinct populations of tissue-resident lymphocytes. Overall design: RNA-seq data were generated for multiple tissues in mice to investigate global expression difference between resident and circulating cells.
Publication Title
Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 1500
Description
Lymphocytic Choriomeningitis Virus (LCMV) specific CD8+ T cells (P14) were transferred into congenic WT mice followed by LCMV(DOCILE) infection. CXCR5-expressing (CXCR5+) or CXCR5 non-expressing (CXCR5-) P14 were purified on day 8 after infection, and total mRNA were sequenced from these populations. mRNA of P14 from uninfected mice (Naive P14) was also sequenced. Overall design: Examination of mRNA level in CXCR5 expressing P14 (CXCR5+P14) and non-expressing P14 (CXCR5-P14) from LCMV infected mice day 8 post infection. mRNA of P14 from uninfected mice (Naïve P14) was also examined.
Publication Title
CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.
Sample Metadata Fields
Subject
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