Phenotypic and functional changes seen in the aged adaptive immune system are primarily driven by aging of hematopoietic stem cells (HSCs), pharmacological rejuvenated aged HSCs were able to reconstituted a youthful immune system Overall design: We employed RNA-seq to assess similarities/differences between naive CD4+ T cells and CD19+ B cells isolated from RAG1-/- recipients transplanted with either young, old or old rejuvenated (CASIN treated) HSCs
Aged murine hematopoietic stem cells drive aging-associated immune remodeling.
Specimen part, Cell line, Subject
View SamplesOf the members of mitochondrial transcription termination factors (mTERFs) found in metazoans and plants known to regulate organellar gene expression at various levels, plant mTERF6 promotes maturation of a tRNA
Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.
No sample metadata fields
View SamplesComparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy
Distinct cardiac transcriptional profiles defining pregnancy and exercise.
Sex, Specimen part
View SamplesPurpose:Heart disease is the number one killer of men and women, but not much is known about baseline differences in the heart between males and females Method: Adult rat ventricular myocytes (ARVMs) were isolated from male and female rats and then RNA was isolated and RNA sequencing was performed. Results: We identified ~ 600 transcripts that were differentially expressed in cardiac myocytes from either sex. We also observed that enriched pathways from this data set were sexually dimorphic Overall design: ARVMs were isolated, plated for 45 minutes and then frozen with liquid nitrogen. We had at least 5 biological replicates for each sex; n=6 males and n=5 females
Transcriptome and Functional Profile of Cardiac Myocytes Is Influenced by Biological Sex.
No sample metadata fields
View SamplesFibrotic diseases have significant health impact and have been associated with differentiation of the resident fibroblasts into myofibroblasts. In particular, stiffened extracellular matrix and TGF-1 in fibrotic lesions have been shown to promote pathogenic myofibroblast activation and progression of fibrosis in various tissues. To better understand the roles of mechanical and chemical cues on myofibroblast differentiation and how they may crosstalk, we cultured primary valvular interstitial cells (VICs) isolated from porcine aortic valves and studied how traditional TCPS culture, which presents a non-physiologically stiff environment, and TGF-1 affect native VIC phenotypes.
Hydrogels preserve native phenotypes of valvular fibroblasts through an elasticity-regulated PI3K/AKT pathway.
Specimen part, Treatment
View SamplesThe perception that soy food products and dietary supplements will have beneficial effects on heart health has led to a massive consumer market. However, we have previously noted that diet has a profound effect on disease progression in a genetic model of hypertrophic cardiomyopathy (HCM). In this model, a soy-based diet negatively impacts cardiac function in male mice.
Remodeling the cardiac transcriptional landscape with diet.
Sex, Specimen part
View SamplesGUN1 integrates retrograde signals in the chloroplast but the underlying mechanism is elusive. FUG1, a chloroplast translation initiation factor, and GUN1 are co-expressed at the transcript level, and FUG1 co-immunoprecipitates with GUN1. We used mutants of GUN1 (gun1-103) and FUG1 (fug1-3) to analyse their functional relationship at the physiological and systems-wide level, the latter including transcriptome and proteome analyses. Absence of GUN1 aggravates the effects of decreased FUG1 levels on chloroplast protein translation, resulting in transient additive phenotypes with respect to photosynthesis, leaf coloration, growth and cold acclimation. Variegation of the var2 mutant is enhanced by gun1-103 in terms of increasing the fraction of white sectors, in contrast to fug1-3 that acts as suppressor. The transcriptomes of fug1-3 and gun1-103 are very similar, but absence of GUN1 alone has almost no effects on protein levels, whereas chloroplast protein accumulation is markedly decreased in fug1-3. In gun1 fug1 double mutants, effects on transcriptomes and particularly proteomes are enhanced. Our results show that GUN1 function becomes critical when chloroplast proteostasis is perturbed by decreased translation (fug1) or degradation (var2) of chloroplast proteins. The functions of FUG1 and GUN1 appear to be related, corroborating the view that GUN1 operates in chloroplast proteostasis. Overall design: Examination of differential gene expression in the Arabdidopsis thaliana gun1, fug1 and gun1 fug1 mutants compared to wild type in three replicates
Relationship of GUN1 to FUG1 in chloroplast protein homeostasis.
Subject
View SamplesChanges ins organellar gene expression trigger retrograde signalling. Prolyl-tRNA synthetase (PRORS1) is located in chloroplasts and mitochondria. Thus, prors1-2 mutants are impaired in chloroplast and mitochondrial gene expression.
Identification of target genes and transcription factors implicated in translation-dependent retrograde signaling in Arabidopsis.
Age, Specimen part
View SamplesA soy diet worsens the progression of an inherited form of hypertrophic cardiomyopathy (HCM) in male mice when compared to casein-fed mice. Females are largely resistant to this diet effect and better preserve cardiac function. We hypothesized that the abundant phytoestrogens found in soy are mainly responsible for this diet-dependent phenotype. Indeed, feeding male mice a phytoestrogen-supplemented casein-based diet can recapitulate the negative outcome seen when male mice are fed a standard soy-based diet.
Estrogenic compounds are not always cardioprotective and can be lethal in males with genetic heart disease.
Sex, Specimen part
View SamplesThe in vitro test battery of the European research consortium ESNATS (novel stem cell-based test systems) has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/ dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test.
Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration.
Sex, Specimen part
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