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SRP047487
Mus musculus
20 Downloadable Samples
Description
Rationale: MicroRNAs play key roles in hypertrophic stress responses. miR-378(-3p) is a highly abundant, cardiomyocyte-enriched microRNA whose downregulation in pressure-overload has been suggested as detrimental to the heart. Previous studies have utilized systemic anti-miR or microRNA-encoding virus administration, and thus questions regarding the cardiomyocyte-autonomous roles of miR-378 remain. Objective: To examine whether persistent overexpression of miR-378 in cardiomyocytes alters the phenotype of the unstressed heart, whether its overexpression is beneficial or deleterious in the setting of pressure-overload, and to comprehensively identify its cardiomyocyte-specific effects on mRNA regulation. Methods and Results: Cardiac function was compared in young (10-12 week-old) mice overexpressing miR-378 in the heart under the control of the Myh6 promoter (alphaMHC-miR-378 mice), in older (40 week-old) mice and their age-matched wild-type controls. Older alphaMHC-miR-378 mice exhibited decreased fractional shortening and modest chamber dilation with an increase in cardiomyocyte length. When subjected to pressure-overload, cardiomyocyte length was increased in young alphaMHC-miR-378 mice, but fractional shortening declined precipitously over two weeks. Transcriptome profiling of wild-type and alphaMHC-miR-378 hearts in unstressed and pressure-overload conditions revealed dysregulation of several upstream metabolic and mitochondrial genes in alphaMHC-miR-378 hearts, compromising the reprogramming that occurs during early adaptation to pressure overload. Ago2 immunoprecipitation with mRNA sequencing revealed novel miR-378 cardiac mRNA targets including Akt1 and Epac2 and demonstrated the contextual nature of previously described miR-378 targeting events. Conclusions: Long-term upregulation of miR-378 levels in the heart is not innocuous and exacerbates contractile dysfunction in pressure-overload hypertrophy through numerous signaling mechanisms. Overall design: Cardiac polyadenylated RNA (mRNA) or RISC-seq (total RNA-seq of Ago2 immunoprecipitate) profiles were generated from nontransgenic and transgenic mouse hearts of FVB/N background, on Illumina HiSeq 2000 instruments. Male mice 8-12 weeks of age were used in these studies, and subjected to sham surgery or 2 weeks of pressure-overload via transverse aortic constriction (TAC). 3 nontransgenic sham, 3 transgenic sham, 7 nontransgenic TAC, 7 transgenic TAC, each with mRNA-seq and RISC-seq data.
Publication Title
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
Description
miR-133a-3p is a highly abundant cardiomyocyte-enriched microRNA whose expression is persistently decreased in response to pressure overload (or transverse aortic constriction, TAC) in mice. Overexpression of miR-133a in cardiomyocytes of mouse hearts in vivo (under the control of the Myh6 promoter) decreases pressure overload-induced apoptosis and fibrosis. In previous studies using microarray platforms, we detected numerous mRNAs whose transcript levels were altered by either or both of miR-133a overexpression and pressure overload. The data set presented here builds upon our previous study in these mice by examining mRNA-RISC associations (using Ago2-immunoprecipitated RNA) and global mRNA abundances via RNA-sequencing procedures, and tests the hypothesis that mRNAs targeted by overexpressed miR-133a are dissimilar between sham and TAC contexts. Overall design: Cardiac polyadenylated RNA (mRNA) profiles were generated from nontransgenic and transgenic mouse hearts of FVB/N background, on Illumina HiSeq 2000 instruments. Male mice 8-12 weeks of age were used in these studies, and subjected to sham surgery or 1 week of pressure-overload via transverse aortic constriction (TAC). 3 nontransgenic sham, 7 transgenic sham, 5 nontransgenic TAC, 4 transgenic TAC, each with mRNA-seq and RISC-seq (mRNA-seq of Ago2 immunoprecipitate) data.
Publication Title
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
A few reports have implicated specific lncRNAs in cardiac development or failure, but precise details of lncRNAs expressed in hearts and how their expression may be altered during embryonic heart development or by adult heart disease is unknown. By comparing lncRNA profiles of normal embryonic (~E14), normal adult, and hypertrophied adult hearts we defined a distinct fetal lncRNA abundance signature that includes 157 lncRNAs differentially expressed compared to adults (fold-change = 50%, FDR=0.02), and which was only poorly recapitulated in hypertrophied hearts (17 differentially expressed lncRNAs; 13 of these observed in embryonic hearts). Analysis of protein-coding mRNAs from the same samples identified 22 concordantly and 11 reciprocally regulated mRNAs within 10 kb of dynamically expressed lncRNAs, reciprocal relationships of lncRNA and mRNA levels was validated for the Mccc1 and Relb genes using in vitro lncRNA knockdown in C2C12 cells. Network analysis suggested a central role for lncRNAs in modulating NFkappaB- and CREB1-regulated genes during embryonic heart growth and identified multiple mRNAs within these pathways that are also regulated, but independently of lncRNAs. Overall design: Cardiac polyadenylated RNA (mRNA and lncRNA) profiles were generated from C57BL/6J mouse hearts were generated on Illumina HiSeq 2000 instruments. 7 independent E13.5 hearts, 12 adult hearts (6 at 6 weeks of age, 6 at 16 weeks of age), 4 sham-operated hearts at 12 weeks of age, and 4 hearts after 4 weeks of pressure overload (TAC) at 12 weeks of age.
Publication Title
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Cells from three adult, wild-type, FVB hearts were separated into cardiomyocyte and nonmyocyte fractions using Langendorff perfusion, collagenase digestion and gravity filtration. Total RNA was prepared immediately from myocytes, while nonmyocytes were passaged twice to yield a culture from which total RNA was prepared. Overall design: 6 cardiac polyadenylated RNA (mRNA and lncRNA) and small RNA (microRNA) profiles of isolated cardiomyocytes (CM) and nonmyocytes (fibro) from 12-wk FVB/NJ mouse hearts were generated on Illumina HiSeq 2000 instruments.
Publication Title
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Next-generation sequencing (NGS) provides for quantitation of RNA abundances and comparison of RNA abundances within tissues and cells in a manner not possible with previous microarray technologies. 5 female mice were subjected to a sham operation, and 5 female mice were subjected to transverse aortic constriction (TAC). After 1 week, hearts were harvested and polyadenylated RNAs were profiled. Analyzed data have been published in Hu et al., Proc Natl Acad Sci USA. 2012;109(48):19864-9, PMID: 23150554 Overall design: 10 cardiac polyA+-RNA profiles of 9 week-old FVB/NJ wild type (WT) mice (5 female sham, 5 female TAC) were generated on Illumina HiSeq 2000 instruments.
Publication Title
Epigenetic coordination of embryonic heart transcription by dynamically regulated long noncoding RNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared TET triple knockdown cells to control cells treated with non-targeting siRNAs to determine global gene expression changes.
Publication Title
Altering TET dioxygenase levels within physiological range affects DNA methylation dynamics of HEK293 cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Androgenic steroids are increasingly used for hormone therapy of postmenopausal women and abused as life style drugs and for doping purposes, though knowledge about associated health risks in females is very limited. In order to understand more about short- and long-term androgen effects on a molecular level, we have analyzed hepatic gene expression in female C57BL/6 mice immediately after subcutaneous treatment with testosterone for 3 weeks and after 12 weeks hormone withdrawal using Affymetrix array technology and quantitative real-time RT-PCR. Among about 14,000 genes examined, 48 were up- and 65 genes were downregulated by testosterone after 3-weeks treatment and about 50% of these changes persisted even 12 weeks after testostrone withdrawal. In addition to obvious risks such as induction of hepatocellular carcinomas and virilization of liver metabolism, testosterone induced a series of changes, as e.g. dysregulation of hepatic gene expression due to incomplete conversion of female to male phenotype in particular downregulation of cytochrom P450 isoforms and sulfotransferases. As a long-term testosterone effect, transcripts emerged in the liver that are normally specific for the exocine pancreas including amylase 2, ribonuclease 1, and several trypsin-, chymotrypsin-, and elastase-like proteases. This transdifferentiation of hepatic to exocrine pancreatic tissue indicates that testosterone can initiate long-lasting differentiation programs, which once induced progress even after androgen withdrawal. This may have far-reaching consequences difficult to foresee implying long-term hazards of testosterone-treatment for female health that have not been taken into account yet.
Publication Title
Testosterone-induced upregulation of miRNAs in the female mouse liver.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarray data to look for gene differentially expressed in the aorta of WT and L-PGDS ko male mice.
Publication Title
Lipocalin-Like Prostaglandin D Synthase but Not Hemopoietic Prostaglandin D Synthase Deletion Causes Hypertension and Accelerates Thrombogenesis in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples