NZB/WF1 female mice spontaneously develop autoimmune lupus nephritis. Expression profiling of kidney tissue from (a) 12 week NZB/W F1 female mice defined as asymptomatic for lupus nephritis, (b) 36 and 42 week NZB/W F1 female mice defined as diseased/symptomatic for lupus nephritis and (c) 36 and 42 week NZB/W F1 female mice that are diseased/symptomatic for lupus nephritis and treated with Sirolimus was carried out. The goal of the study was to identify genes associated with lupus nephritis and modulated by Sirolimus, an inhibitor of mTOR. In addition, lupus nephritis genes resistant to Sirolimus therapy were also identfied
Mapping similarities in mTOR pathway perturbations in mouse lupus nephritis models and human lupus nephritis.
Sex, Specimen part, Disease, Treatment, Time
View SamplesBackground. Vaginal atrophy (VA) is the thinning of the vaginal epithelial lining, typically the result of lowered estrogen levels during menopause. Some of the consequences of VA include increased susceptibility to bacterial infection, pain during sexual intercourse, and vaginal burning or itching. Although estrogen treatment is highly effective, alternative therapies are also desired for women who are not candidates for hormone replacement therapy (HRT). The ovariectomized (OVX) rat is widely accepted as an appropriate animal model for many estrogen-dependent responses in humans; however, since reproductive biology can vary significantly between mammalian systems, this study examined how well the OVX rat recapitulates human biology at the transcriptional level. This report describes an analysis of expression profiling data, comparing the responses of rat and human vaginae to estrogen treatment. Results. The level of differential expression between pre- vs. post- estrogen treatment was calculated for each of the human and OVX rat datasets. Probe sets corresponding to orthologous rat and human genes were mapped to each other using NCBI Homologene. A positive correlation was observed between the rat and human responses to estrogen. Genes belonging to several biological pathways and GO categories were similarly differentially expressed in rat and human. A large number of the coordinately regulated biological processes are already known to be involved in human VA, such as inflammation, epithelial development, and EGF pathway activation. Conclusions. At the transcriptional level, there is evidence of significant overlap of the effects of estrogen treatment between the OVX rat and human VA samples.
Molecular analysis of the vaginal response to estrogens in the ovariectomized rat and postmenopausal woman.
Age
View SamplesRNA-sequencing performed on petals and inflorescence of Arabidopsis plants. The study provides insight into the role of the TCP5 transcription factor and its molecular mechanism underlying petal growth, using knock-out, overexpression and induction lines on which RNA-sequencing was performed. Overall design: Analysis of differential gene expression using petals from TCP5 overexpression and knockout lines, as well as inflorescences of an inducible TCP5 mutant.
Novel functions of the Arabidopsis transcription factor TCP5 in petal development and ethylene biosynthesis.
Specimen part, Subject
View SamplesThe behavior of yeast cells during industrial processes such as the production of beer, wine and bioethanol has been extensively studied. By contrast, our knowledge about yeast physiology during solid state processes, such as bread dough, cheese or cocoa fermentation remains limited. We investigated changes in the transcriptome of three genetically distinct Saccharomyces cerevisiae strains during bread dough fermentation. Our results show that regardless of the genetic background, all three strains exhibit similar changes in expression patterns. At the onset of fermentation, expression of glucose-regulated genes changes dramatically, and the osmotic stress response is activated. The middle fermentation phase is characterized by the induction of genes involved in amino acid metabolism. Finally, at the latest time point, cells suffer from nutrient depletion and activate pathways associated with starvation and stress response. Further analysis shows that genes regulated by the High Osmolarity Glycerol (HOG) pathway, the major pathway involved in the response to osmotic stress and glycerol homeostasis, are among the most differentially expressed genes at the onset of fermentation. More importantly, deletion of HOG1 and other genes of this pathway significantly reduces fermentation capacity. Together, our results demonstrate that cells embedded in a solid matrix such as bread dough suffer severe osmotic stress, and that a proper induction of the HOG pathway is critical for an optimal fermentation.
Dynamics of the Saccharomyces cerevisiae transcriptome during bread dough fermentation.
No sample metadata fields
View SamplesPurpose: 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. We have made widespread use of Illumina sequencing technologies for RNA quantitation in several publications involving mouse hearts, dating from 2010, and wish to share both high-quality raw sequencing data and data processed to quantitate mRNA abundances from wild-type mice, male and female, at a variety of ages. These data will provide a resource for investigators using microarrays to understand the concentration of transcripts of interest relative to other cardiac RNAs, and will permit deeper interpretation of previous microarray studies. Overall design: 39 cardiac small RNA (microRNA) profiles of 4- to 16 week-old FVB/NJ wild type (WT) mice were generated on Illumina HiSeq 2000 instruments.
Great Expectations: MicroRNA-30d and Cardiac Resynchronization Therapy.
No sample metadata fields
View SamplesAdult mice bearing homozygous floxed Parkin alleles (PMIDs 15249681, 21376232; T M Dawson), with or without the Myh6-driven MERCreMER transgene, were administered tamoxifen at 6-10 wks of age. Tissues were obtained from euthanized mice 9-10 weeks after tamoxifen induction. Overall design: 6 floxed, non-Cre (noninduced) mouse hearts; 6 floxed, MERCreMer, adult-induced, Parkin knockout mouse hearts
Central Parkin: The evolving role of Parkin in the heart.
Specimen part, Subject, Time
View SamplesDysfunctional Parkin-mediated mitophagic culling of senescent or damaged mitochondria is a major pathological process underlying Parkinson disease and a potential genetic mechanism of cardiomyopathy. Despite epidemiological associations between Parkinson disease and heart failure, the role of Parkin and mitophagic quality control in maintaining normal cardiac homeostasis is poorly understood.We used germline mutants and cardiac-specific RNA interference to interrogate Parkin regulation of cardiomyocyte mitochondria and examine functional crosstalk between mitophagy and mitochondrial dynamics in Drosophila heart tubes. Overall design: 5 wild-type mouse hearts; 4 germline Parkin knockout mouse hearts Please note that the mouse cardiac examples were an adjunct to the Drosophila studies that comprised most of the associated publication. However, mRNA-sequencing was only performed on the mouse samples, not the Drosophila heart tubes.
Central Parkin: The evolving role of Parkin in the heart.
Specimen part, Subject
View SamplesPurpose: 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. We have made widespread use of Illumina sequencing technologies for RNA quantitation in several publications involving mouse hearts, dating from 2010, and wish to share both high-quality raw sequencing data and data processed to quantitate mRNA abundances from wild-type mice, male and female, at a variety of ages. These data will provide a resource for investigators using microarrays to understand the concentration of transcripts of interest relative to other cardiac RNAs, and will permit deeper interpretation of previous microarray studies. Overall design: 6 cardiac small RNA (microRNA) profiles of 18 week-old C57BL/6J wild type (WT) mice were generated on Illumina HiSeq 2000 instruments.
Menage a Trois: intimate relationship among a microRNA, long noncoding RNA, and mRNA.
No sample metadata fields
View SamplesPurpose: 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. We have made widespread use of Illumina sequencing technologies for RNA quantitation in several publications involving mouse hearts, dating from 2010, and wish to share both high-quality raw sequencing data and data processed to quantitate mRNA abundances from wild-type mice, male and female, at a variety of ages (see our FVB/NJ data submission). These data will provide a resource for investigators using microarrays to understand the concentration of transcripts of interest relative to other cardiac RNAs, and will permit deeper interpretation of previous microarray studies. Overall design: 4 cardiac polyA+-RNA profiles of 12 week-old C57BL/6J wild type (WT) mice were generated on Illumina HiSeq 2000 instruments.
Menage a Trois: intimate relationship among a microRNA, long noncoding RNA, and mRNA.
No sample metadata fields
View SamplesRationale: 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.
Cardiac Disease Status Dictates Functional mRNA Targeting Profiles of Individual MicroRNAs.
No sample metadata fields
View Samples