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SRP090696
Caenorhabditis elegans
20 Downloadable Samples
Illumina HiSeq 1500
Description
Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means. Overall design: Synchronized, starved L1 stage worms were grown on NGM plates under one of two conditions. Condition 1: growth was at 20°C (hpl-2, let-418, lin-61, met-2 set-25, and wild-type N2) until the L4 stage and then worms were shifted to 25°C for 15-18 hours until they reached young adult stage. Condition 2: growth was at 15°C (lin-13, prg-1, nrde-2, nrde-2; let-418, and wild-type N2) until the L4 stage, and then worms were shifted to 25°C for 15-18 hours until they reached young adult stage. Worms were then washed off plates, flash frozen in liquid nitrogen, and stored at -80°C until use. RNA was extracted from frozen worms using TriPure (Roche). RNA was purified with Zymo Research RNA Clean and Concentrator-5 (Cambridge Bioscience) following DNase I digestion. Ribosomal RNA was depleted using Ribo-Zero rRNA Removal Kit (Human/Mouse/Rat) (Illumina). Libraries were prepared using the NEBNext Ultra Directional RNA Library Prep Kit for Illumina (New England Biolabs). Two biological replicates were prepared for each strain.
Publication Title
A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 25 Downloadable Samples
- Illumina HiSeq 4000
Description
Women suffer chronic pain more frequently than men. It is not clear whether this is due to differences in higher level cognitive processes or basic nociceptive responses. This study used a mouse model to dissociate these factors and found no differences in peripheral afferent neurons or in the spinal cord immune response to neuropathic injury. However, it did identify potential sexual dimorphisms in peripheral adaptive immune responses. Overall design: RNA-seq of naïve FACS-purified DRG neurons and MACS-purified DRG neurons after partial sciatic nerve ligation (day 8): comparison of male versus female samples
Publication Title
Sex differences in peripheral not central immune responses to pain-inducing injury.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 199 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Notch signaling plays both oncogenic and tumor suppressor roles, depending on cell type. In contrast to T cell acute lymphoblastic leukemia (T-ALL), where Notch activation promotes leukemogenesis, induction of Notch signaling in B-ALL leads to growth arrest and apoptosis. The Notch target Hairy/Enhancer of Split1 (HES1) is sufficient to reproduce this tumor suppressor phenotype in B-ALL, however the mechanism is not yet known. Here we report that HES1 regulates pro-apoptotic signals via the novel interacting protein Poly ADP-Ribose Polymerase1 (PARP1) in a cell type-specific manner. The interaction of HES1 with PARP1 inhibits HES1 function, induces PARP1 activation and results in PARP1 cleavage in B-ALL. HES1-induced PARP1 activation leads to self-ADP ribosylation of PARP1, consumption of NAD+, diminished ATP levels, and translocation of the Apoptosis Inducing Factor (AIF) from mitochondria to the nucleus, resulting in apoptosis in B-ALL, but not T-ALL. Importantly, induction of Notch signaling via the Notch agonist peptide DSL can reproduce these events and leads to BALL apoptosis. The novel interaction of HES1 and PARP1 in B-ALL modulates the function of the HES1 transcriptional complex and signals through PARP1 to induce apoptosis. This mechanism reveals a cell type-specific pro-apoptotic pathway which may lead to Notch agonist-based cancer therapeutics.
Publication Title
Notch/HES1-mediated PARP1 activation: a cell type-specific mechanism for tumor suppression.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Understanding the molecular underpinnings of cancer is of critical importance to developing targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multi-faceted cellular phenotype thus only have been identified following signaling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signaling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state. Remarkably, 14 among 24 such 'cooperation response genes' (CRGs) were found to contribute to tumor formation in gene perturbation experiments. In contrast, only one in 14 perturbations of genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain and loss-of-function mutations.
Publication Title
Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Leukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown.
Publication Title
Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 335 Downloadable Samples
- NextSeq 500
Description
Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. The principal neural unit in the bowel encoding these stimuli is the visceral sensory neuron with endings at the mucosa, intramurally and along mesenteric blood vessels. Sensory neurons activate reflex pathways and give rise to conscious sensation, however, the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by the current paucity of molecular markers. Here we overcome these limitations by comprehensive transcriptomic profiling and unsupervised clustering of single colonic sensory neurons revealing 7 classes characterised from both lumbar splanchnic (LSN) and pelvic nerves (PN). We identify and classify neurons based on novel marker genes, confirm translation of patterning to protein expression and show subtype-selective differential agonist activation, describing sensory diversity encompassing all modalities of colonic neuronal sensitivity. Overall design: Sensory neurons innervating the mouse colorectum were labelled by retrograde tracer injection. Single-cell RNAseq was performed on 399 dissociated colonic sensory neurons isolated from thoracolumbar (T10-L1) and lumbosacral (L5-S2) dorsal root ganglia distributed over six 96-well plates. 13 additional negative controls were collected.
Publication Title
Single-cell RNAseq reveals seven classes of colonic sensory neuron.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- NextSeq 500
Description
mRNA-sequencing from ribosomal RNA-depleted cardiac total RNA was performed 9 weeks after injection of rAAV6-PLCb1a, rAAV6-PLCb1b or rAAV6-blank viri into the tail vein of C57BL/6 male mice (7-8 weeks of age at time of injection). Overall design: 6 biological replicates each of rAAV6-PLCb1a, rAAV6-PLCb1b or rAAV6-blank-treated mice.
Publication Title
Chronic Contractile Dysfunction without Hypertrophy Does Not Provoke a Compensatory Transcriptional Response in Mouse Hearts.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 59 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
This dataset is a time series (1 hour [h], 4 hours, 24 hours, 48 hours, 1 week [w], and 8 weeks) intended to compare normal functioning left ventricles [lv + lv2] with infarcted [ilv] and non-infarcted left ventricles [nilv]. Ilv samples are taken from the region between the LAD artery and the apex on a mouse with myocardial infarction. Lv2 samples are from the same region in a sham operated mouse. Nilv samples are taken from the region above the infartion and the left ventricle [lv] samples mimic that region in a sham mouse. The lv and lv2 samples can be compared as both are from normal functioning hearts. For more information visit http://cardiogenomics.med.harvard.edu/groups/proj1/pages/mi_home.html
Publication Title
Mouse cardiac surgery: comprehensive techniques for the generation of mouse models of human diseases and their application for genomic studies.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
Publication Title
Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
MYC is induced early in human adipose stem cells in response to a standard MDIR adipogenic cocktail. The objective of this experiment was to identify key gene networks impacted by MYC loss-of-function in a mixed donor pool of human derived adipose stem cells.
Publication Title
MYC is an early response regulator of human adipogenesis in adipose stem cells.
Sample Metadata Fields
Sex, Race
View Samples