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SRP012411
Bos taurus
47 Downloadable Samples
Illumina Genome Analyzer II
Description
Background: Weaning of beef calves is a necessary husbandry practice and involves separating the calf from its mother, resulting in numerous stressful events including dietary change, social reorganisation and the cessation of the maternal-offspring bond and is often accompanied by housing. While much recent research has focused on the physiological response of the bovine immune system to stress in recent years, little is known about the molecular mechanisms modulating the immune response. Therefore, the objective of this study was to provide new insights into the molecular mechanisms underlying the physiological response to weaning at housing in beef calves using Illumina RNA-seq. Results: The leukocyte transcriptome was significantly altered for at least 7 days following either housing or weaning at housing. Analysis of differentially expressed genes revealed that four main pathways, cytokine signalling, transmembrane transport, haemostasis and G-protein-coupled receptor (GPRC) signalling, were differentially regulated between control and weaned calves and underwent significant transcriptomic alterations in response to weaning stress on day 1, 2 and 7. Of particular note, chemokines, cytokines and integrins were consistently found to be up-regulated on each day following weaning. Evidence for alternative splicing of genes was also detected, indicating that a number of genes involved in the innate and adaptive immune response may be alternatively transcribed, including those responsible for toll receptor cascades and T cell receptor signalling. Conclusions: This study represents the first application of RNA-Seq technology for genomic studies in bovine leukocytes in response to weaning stress. Weaning stress induces the activation of a number of cytokine, chemokine and integrin transcripts and may alter the immune system whereby the ability of a number of cells of the innate and adaptive immune system to locate and destroy pathogens is transcriptionally enhanced. Stress alters the homeostasis of the transcriptomic environment of leukocytes for at least 7 days following weaning, indicating long-term effects of stress exposure in the bovine. The identification of gene signature networks that are stress activated provides a mechanistic framework to characterise the multifaceted nature of weaning stress adaptation in beef calves. Thus, capturing subtle transcriptomic changes provides insight into the molecular mechanisms that underlie the physiological response to weaning stress. Overall design: Examination of a time course (day 0, 1, 2 and 7) for 2 treatments, calves either housed with their dam (control) or housed and simultaneously weaned, using RNA-seq. The supplementary processed data file 'read_counts.txt' contains unnormalized read counts for each Ensembl bovine gene in each of the 48 samples. Unnormalized counts are required for input to EdgeR. Genome build: Btau4.0
Publication Title
Transcriptomic analysis of the stress response to weaning at housing in bovine leukocytes using RNA-seq technology.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We identified 201 genes that are consistently upregulated more than 20%, and 108 genes that are consistently downregulated more than 20% in the miR-205 KO samples in two sets of biological duplicates.
Publication Title
MicroRNA-205 controls neonatal expansion of skin stem cells by modulating the PI(3)K pathway.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA.
Publication Title
Rapid and widespread suppression of self-renewal by microRNA-203 during epidermal differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
- NextSeq 500
Description
Microglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
Publication Title
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- NextSeq 500
Description
Microglia play a pivotal role in the maintenance of brain homeostasis, but lose their homeostatic function during the course of neurodegenerative disorders. We identified a specific APOE-dependent molecular signature in microglia isolated from mouse models of amyotrophic lateral sclerosis, multiple sclerosis and Alzheimer’s disease (SOD1, EAE and APP-PS1) and in microglia surrounding neuritic A?-plaques in human Alzheimer’s disease brain. This is mediated by a switch from a (M0)-homeostatic to (MGnD)-neurodegenerative phenotype following phagocytosis of apoptotic neurons via the TREM2-APOE pathway. TREM2 induces APOE signaling which is a negative regulator of the transcription program in M0-homeostatic microglia. Targeting the TREM2-APOE pathway restores the M0-homeostatic signature of microglia in APP-PS1 and SOD1 mice and prevents from neuronal loss in an acute model of neurodegeneration. In SOD1 mice, TREM2 regulates MGnD in a gender-dependent manner. APOE-mediated MGnD microglia lose their tolerogenic function. Taken together, our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target to restore homeostatic microglia. Overall design: Illumina NextSeq500 was used to identify disease-associated vs. homeostatic molecular microglia signature in microglia in different disease models and transgenic models. Bulk microglia (1,000 cells/sample) FCRLS+ sorted microglia.
Publication Title
The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
SOX2 is an oncogene and a core pluripotency transcription factor. SOX2 has multiple roles in various malignancies, in the maintainance of pluripotency and during various stages of embryonic development. Human embryonal carcinoma cells express SOX2 and the loss of this results in their differentiation.
Publication Title
An integrated analysis of the SOX2 microRNA response program in human pluripotent and nullipotent stem cell lines.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Analysis of mouse placenta retrieved at day 18.5pc from vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr) knockout, heterozygous and wild-type mice. Results provide insight into the molecular mechanisms underlying the effect of vitamin D on placental function.
Publication Title
Vitamin D Receptor Gene Ablation in the Conceptus Has Limited Effects on Placental Morphology, Function and Pregnancy Outcome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors alpha (ERalpha) and beta (ERbeta), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene sets the expression of which is regulated by long-term (1 wk) estrogen treatment. The ER subtype dependence of the alterations in gene expression was characterized by parallel gene expression profiling experiments in ERalpha-deficient [ERalpha knockout (ERalphaKO)] and ERbeta-deficient (ERbetaKO) mice.
Publication Title
Estrogen receptors alpha and beta mediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
RNA-directed DNA methylation (RdDM) is a transcriptional silencing mechanism mediated by small and long noncoding RNAs produced by the plant-specific RNA polymerases Pol IV and Pol V, respectively. Through a chemical genetics screen with a luciferase-based DNA methylation reporter, LUCL, we found that camptothecin, a compound with anti-cancer properties that targets DNA topoisomerase 1a (TOP1a) was able to de-repress LUCL by reducing its DNA methylation and H3K9 dimethylation (H3K9me2) levels. Further studies with Arabidopsis top1a mutants showed that TOP1a promotes RdDM by facilitating the production of Pol V-dependent long non-coding RNAs, AGONAUTE4 recruitment and H3K9me2 deposition at transposable elements (TEs). Overall design: 5 small RNA libraries were sequenced
Publication Title
DNA topoisomerase 1α promotes transcriptional silencing of transposable elements through DNA methylation and histone lysine 9 dimethylation in Arabidopsis.
Sample Metadata Fields
Specimen part, Subject
View Samples