Filters
Technology
Platform
SRP048535
Mus musculus
17 Downloadable Samples
Illumina HiSeq 2000
Description
We sequenced mRNA from three age groups (3months (3M), 24 months (24M) and 29 months (29M)) from the full hippocampus Overall design: There were two independent experiments: 3M vs 24M (n=5 to 6, single-end sequencing) and 3M vs 29M (n=3, paired-end sequencing))
Publication Title
De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
Cultured pluripotent stem cells are a cornerstone of regenerative medicine due to their ability to give rise to all cell types of the body. While pluripotent stem cells can be propagated indefinitely in vitro, pluripotency is paradoxically a very transient state in vivo, lasting 2-3 days around the time of blastocyst implantation. The exception to this rule is embryonic diapause, a reversible state of suspended development triggered by unfavorable conditions. Diapause is a strategy widely employed across the animal kingdom, including in mammals, but its regulation remains poorly understood. Here we report that inhibition of mechanistic target of rapamycin (mTor), a major nutrient sensor and promoter of growth, induces reversible pausing of mouse blastocyst development and allows their prolonged culture ex vivo. Paused blastocysts remain pluripotent and competent to give rise to embryonic stem (ES) cells and mice. We show that both natural diapause blastocysts in vivo and paused blastocysts ex vivo display pronounced reductions in mTor activity, translation and transcription. In addition, pausing can be induced directly in cultured ES cells and sustained for weeks in the absence of cell death or deviations from cell cycle distributions. We show that paused ES cells remain pluripotent, display a remarkable global suppression of transcription, and maintain a gene expression signature of diapaused blastocysts. These results allow for the first time the sustained suspension of development of a mammalian embryo in the laboratory, and shed light on the regulation of diapause and the origins of ES cells. Our findings have important implications in the fields of assisted reproduction, regenerative medicine, cancer, metabolic disorders and aging. Overall design: Examination of RNA expression profiles of embryonic stem cells in serum, 2i and paused states by RNA-seq
Publication Title
Inhibition of mTOR induces a paused pluripotent state.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer’s disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia. Overall design: Role of Fmn2 gene for PTSD like phenotypes and impairments of synaptic plasticity.
Publication Title
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Homo sapiens
- 42 Downloadable Samples
- IlluminaHiSeq2000
Description
Roberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2. We previously reported that mTORC1 was inhibited and overall translation was reduced in RBS cells. Treatment of RBS cells with L-leucine partially rescued mTOR function and protein synthesis, correlating with increased cell division. In this study, we use RBS as a model for mTOR inhibition and analyze transcription and translation with ribosome profiling to determine genome-wide effects of L-leucine. The translational efficiency of many genes is increased with Lleucine in RBS cells including genes involved in ribosome biogenesis, translation, and mitochondrial function. snoRNAs are strongly upregulated in RBS cells, but decreased with L-leucine. Imprinted genes, including H19 and GTL2, are differentially expressed in RBS cells consistent with contribution to mTORC1 control. This study reveals dramatic effects of L-leucine stimulation of mTORC1 and supports that ESCO2 function is required for normal gene expression and translation. Overall design: 42 samples of human fibroblast cell lines with various genotypes (wt, corrected, and esco2 mutants) are treated with l-leucine or d-leucine (control) for 3 or 24 hours. Biological replicates are present.
Publication Title
Improved transcription and translation with L-leucine stimulation of mTORC1 in Roberts syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to impact gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that can prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor a binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of different ERBS combinations identified supportive ERBS that contribute only when predominant sites are active. Using mathematical modeling, we find strong evidence for collaboration between predominant and supportive ERBS. Overall, our findings expose a complex functional hierarchy of enhancers, where multiple loci bound by the same transcription factor combine to fine tune the expression of target genes. Overall design: The effects of Enhancer interference (Enhancer-i) and control guide RNA treatment on the transcriptome before and after estrogen treatment, with 2 replicates per condition.
Publication Title
Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Cohesinopathies are characterized by mutations in the cohesin complex. Mutations in NIPBL, a cohesin loader, result in Cornelia de Lange syndrome (CdLS). CdLS is a congenital genetic disorder distinguished by craniofacial dysmorphism, abnormal upper limb development, delayed growth, severe cognitive retardation, and multiple organ malformations.It has been suggested that CdLS is caused by defects in the cohesin network that alter gene expression and genome organization. However, the precise molecular etiology of CdLS is largely unclear. To gain insights, we sequenced mRNAs isolated from mouse embryonic fibroblasts of both WT and NIPBL-haploinsufficient mice and compared their transcriptomes. Overall design: Examination of gene expression of WT and NIPBL+/- mice by RNA-seq
Publication Title
NIPBL Controls RNA Biogenesis to Prevent Activation of the Stress Kinase PKR.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Condensin complexes are highly conserved for chromosome compaction to ensure their faithful segregation in mitosis. Condensin II is present in the nucleus throughout the cell cycle, including interphase. The aim of these experiments is to investigate the changes of gene expression in knockdown of NCAPH2, a condensin II subunit, in mouse embryonic stem cells compared to their control cells. Overall design: Examination of gene expression of controls and NCAPH2 knockdown cells by RNA-seq
Publication Title
Condensin II is anchored by TFIIIC and H3K4me3 in the mammalian genome and supports the expression of active dense gene clusters.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 292 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 282 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to profile the expression levels of 285 ovarian samples in order to identify molecular subtypes of the tumour
Publication Title
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to profile the expression levels of 5 tumour samples
Publication Title
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
Sample Metadata Fields
No sample metadata fields
View Samples