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SRP179743
Homo sapiens
18 Downloadable Samples
Illumina HiSeq 2000
Description
The PLZF transcription factor is essential for osteogenic differentiation of hMSCs, however, its regulation and molecular function during this process is not fully understood. Here we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naïve hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation. Overall design: Effect of PLZF knockdown on osteogenic differentiation of hMSC (RNAseq)
Publication Title
PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Skeletal muscle microRNA and messenger RNA profiling in cofilin-2 deficient mice reveals cell cycle dysregulation hindering muscle regeneration.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
mRNA Expression in Quadriceps Muscle from Cofilin-2 Null Mice Compared to WT Littermates on Day 7
Publication Title
Skeletal muscle microRNA and messenger RNA profiling in cofilin-2 deficient mice reveals cell cycle dysregulation hindering muscle regeneration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Dendritic cells (DCs) are major antigen-presenting cells that play a key role in initiating and regulating innate and adaptive immune responses. DCs are critical mediators of tolerance and immunity. The functional properties of DCs changes with age.
Publication Title
Alterations in gene array patterns in dendritic cells from aged humans.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: Personalized medicine is predicated on the notion that individual biochemical and genomic profiles are relatively constant in times of good health and to some extent predictive of disease or therapeutic response. We report a pilot study quantifying gene expression and methylation profile consistency over time, addressing the reasons for individual uniqueness, and its relation to N=1 phenotypes. Methods: Whole blood samples from 4 African American women, 4 Caucasian women, and 4 Caucasian men drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays. Standard regression approaches were used to evaluate the proportion of variance for each type of omic measure that is among individuals, and to quantify correlations among measures and with clinical attributes related to wellness. Results: Longitudinal omic profiles are in general highly consistent over time, with an average of 67% of the variance in transcript abundance, 42% of CpG methylation level (but 88% for the most differentiated CpG per gene), and 50% of miRNA abundance among individuals, which are all comparable to 74% of the variance among individuals for 74 clinical traits. One third of the variance can be attributed to differential blood cell type abundance, which is also fairly stable over time, and a lesser amount to eQTL effects, whereas seven conserved axes of covariance that capture diverse aspects of immune function explain over half of the variance. These axes also explain a considerable proportion of individually extreme transcript abundance, namely approximately 100 genes that are significantly up- or down-regulated in each person and are in some cases enriched for relevant gene activities that plausibly associate with clinical attributes. A similar fraction of genes have individually divergent methylation levels, but these do not overlap with the transcripts, and fewer than 20% of genes have significantly correlated methylation and gene expression. Conclusions: People express an “omic personality” consisting of peripheral blood transcriptional and epigenetic profiles that are constant over the course of a year and reflect various types of immune activity. Baseline genomic profiles can provide a window into the molecular basis of traits that might be useful for explaining medical conditions or guiding personalized health decisions. Overall design: Whole blood samples from 12 subjects drawn from the Atlanta Center for Health Discovery and Well Being study at three successive 6-month intervals were profiled by RNASeq, miRNASeq, and Illumina Methyl-450 arrays.
Publication Title
Omic personality: implications of stable transcript and methylation profiles for personalized medicine.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
To investigate the effects of TBI on affecting the gene expressions in the hippocampus of male SD rats by RNA-Seq.. Overall design: Male Sprague–Dawley (SD) rats weighing between 200 and 240 g were housed in cages and maintained in environmentally-controlled rooms (22–24C) with a 12-h light/dark cycle. After acclimatization for 1 week on standard rat chow, the rats were subjected to TBI by fluid percussion injury (FPI) or sham surgery. At 1 week post-surgery the rats were tested for learning abilities, and then were sacrificed by decapitation. The fresh tissues including the hippocampus were dissected out, flash frozen, and stored at -70°C for later transcriptome and DNA methylome sequencing experiments. All experiments were performed in accordance with the United States National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the University of California at Los Angeles Chancellor’s Animal Research Committee.
Publication Title
Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 86 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We tested the hypothesis that a set of differentially expressed genes could be used to predict cardiovascular phenotype in mice after prolonged catecholamine stress.
Publication Title
Gene expression profiling: classification of mice with left ventricle systolic dysfunction using microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 21 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
A comparison of microarray and MPSS technologies can help to establish the metrics for data comparisons across these technology platforms and determine some of the factors affecting the measurement of mRNA abundances using different platforms. Here, different Treatments/Conditions based on different Arabidopsis tissues were used for three different platforms include MPSS, Affymetrix and Agilent.
Publication Title
A comparison of microarray and MPSS technology platforms for expression analysis of Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Illumina HiSeq 2500
Description
Recurrent mutations in RNA splicing factors SF3B1, U2AF1, and SRSF2 have been reported in hematologic cancers including myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). However, SF3B1 is the only splicing associated gene to be found mutated in CLL and has been shown to induce aberrant splicing. To investigate if any other genomic aberration caused similar transcriptome changes, we clustered RNASeq samples based on an alternative 3' splice site (ss) pattern previously identified in SF3B1-mutant CLL patients. Out of 215 samples, we identified 37 (17%) with alternative 3' ss usage, the majority of which harbored known SF3B1 hotspot mutations. Interestingly, 3 patient samples carried previously unreported in-frame deletions in SF3B1 around K700, the most frequent mutation hotspot. To study the functional effects of these deletions, we used various minigenes demonstrating that recognition of canonical 3' ss and alternative branchsite are required for aberrant splicing, as observed for SF3B1 p.K700E. The common mechanism of action of these deletions and substitutions result in similar sensitivity of primary cells towards splicing inhibitor E7107. Altogether, these data demonstrate that novel SF3B1 in-frame deletion events identified in CLL result in aberrant splicing, a common biomarker in spliceosome-mutant cancers. Overall design: 13 CLL samples, 5 SF3B1 WT, 5 SF3B1 p.K700E, and 3 with in-frame deletions around the K700 position of SF3B1
Publication Title
Novel <i>SF3B1</i> in-frame deletions result in aberrant RNA splicing in CLL patients.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Rattus norvegicus
- 5 Downloadable Samples
Description
The heart adapts to increased workload through hypertrophic growth of cardiomyocytes. Although beneficial when induced physiologically by exercise, pathological cues including hypertension cause reexpression of fetal genes and dysfunctional hypertrophy, with lasting consequences for cardiac health. We hypothesised that these differences are driven by changes in chromatin-encoded cellular memory. We generated genome-wide maps of transcription and of two stable epigenetic marks, H3K9me2 and H3K27me3, specifically in hypertrophied cardiomyocytes, by selectively flow-sorting their nuclei. This demonstrated a pervasive loss of euchromatic H3K9me2 specifically upon pathological but not physiological hypertrophy, derepressing genes associated with pathological hypertrophy. Levels of the H3K9 methyltransferases, G9a and GLP, were correspondingly reduced. Importantly, pharmacological or genetic inactivation of these enzymes was sufficient to induce pathological hypertrophy and the dedifferentiation associated with it. These findings suggest novel therapeutic opportunities by defining an epigenetic state of cardiomyocytes, acquired during maturation, which is required for maintaining cardiac health. Overall design: Examination of 2 different histone modifications and RNA expression in cardiomyocyte nuclei flow-sorted from hypertrophic rat hearts
Publication Title
The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.
Sample Metadata Fields
No sample metadata fields
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