A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism.
Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.
Sex, Age, Specimen part
View SamplesGene expression changes in 3 human melanoma cell lines were compared to freshly isolated normal primary melanocytes Overall design: Three biological replicates for each melanoma cell line and primary melanocytes were labeled and run Illumina HiSeq2500. The transcriptome of melanocytes was compared to cell line SK-Mel-28, SK-Mel-147 or UACC-62.
Systems analysis identifies melanoma-enriched pro-oncogenic networks controlled by the RNA binding protein CELF1.
Specimen part, Subject
View SamplesThese data represents a microgenomic approach to dissect the response of the plant steroid hormone, brassinosteroid, in the provascular tissue of the arabidopsis thaliana primary roots. We used two different provascular markers, wooden leg (WOL) and corona (ATHB15) to profile the provascular response to BRs. We used a timecourse analysis with 4 different timepoint; 0.5, 1, 2 and 4 hours treated with BRs in the WOL domain. Additional trasncriptomic responses of the ATHB15 domain were analyzed after 2 hours BRs treatment.
Regulation of plant stem cell quiescence by a brassinosteroid signaling module.
Specimen part, Time
View SamplesAbstract: Drought is the primary cause of global agricultural losses and represents a major threat to worldwide food security. Currently, plant biotechnology stands out as the most promising strategy to increase crop growth in rain-fed conditions. The main mechanisms underlying drought resistance have been uncovered by studies of plant physiology and by engineering crops with drought-resistant genes. However, plants with enhanced drought resistance usually display lower levels of growth, highlighting the need to search for novel strategies capable of uncoupling drought resistance from growth. Here, we show that the brassinosteroid family of receptors, in addition to promoting growth, guides phenotypic adaptation to a great variety of drought stress traits analyzed herein. Whilst mutations in the ubiquitously localized BRI1 receptor pathway show an enhanced drought resistance at the expense of plant growth, we found that vascular-enriched BRL3 receptors confer drought tolerance without penalizing overall growth. Systematic analyses reveal that upon drought stress the BRL3 receptor pathway triggers the synthesis and mobilization of osmoprotectant metabolites, mainly proline and sugars. This preferentially occurs in the vascular tissues of the roots and favors overall plant growth. Altogether, our results uncover a new role for the spatial control of BR signaling in drought tolerance, and offer a novel strategy to address food security issues in an increasingly water-limited climate. Overall design: 28 days old root system were collected from soil, quickly washed in water and flash-frozen. Experiment with a bifactorial design. Factor one is the genotype, which include WT (Col-0) and 35S:BRL3. Factor two is the condition, which include control (Properly watered) and 5 days of drought (water-hold) conditions. 3 Biological replicates were collected per each genotype and condition.
Overexpression of the vascular brassinosteroid receptor BRL3 confers drought resistance without penalizing plant growth.
Specimen part, Subject
View SamplesWe have previously reported that tyrosol (TYR), one of the main phenols in extra virgin olive oil (EVOO), promotes lifespan extension in the nematode Caenorhabditis elegans, also inducing a stronger resistance to thermal and oxidative stress in this animal model. Although the influence of several longevity-related genes in these effects has been reported by our group, we decided to perform a whole genome DNA-microarray approach in order to identify other genes and molecular pathways further involved in TYR effects on C. elegans longevity. Microarray analysis identified 208 differentially expressed genes (206 overexpressed and 2 underexpressed) when comparing TYR-treated nematodes with non-treated controls. Many of these genes seem linked to processes such as regulation of growth, transcription, reproduction, lipid metabolism and body morphogenesis. Data obtained by microarray was validated by qRT-PCR analysis of selected genes. Our results confirm that several important cellular mechanisms related to longevity are influenced by TYR treatment in this animal model. Moreover, we detected an interesting overlap between the expression pattern elicited by TYR and those induced by other dietary polyphenols known to extend lifespan in C. elegans, such as quercetin and tannic acid.
Gene expression profiling to investigate tyrosol-induced lifespan extension in Caenorhabditis elegans.
Treatment
View SamplesExponentially growing cells and type II persister cells from the DS1-(hipQ)-strain
Novel protocol for persister cells isolation.
Specimen part, Disease, Cell line
View SamplesThe data presented is intended to analyse the changes in the expression profiles of human MSCs (Mesenchymal Stromal/Stem Cells) associated to different tissue specific stimulus.
Insights into the human mesenchymal stromal/stem cell identity through integrative transcriptomic profiling.
Specimen part
View SamplesCharacterization of genes associated with adipose tissue is key to understanding the pathogenesis of obesity and developing treatments for this disorder. Differential gene expression in the adipose tissue has been described in adulthood but none studies have been developed on childhood. The purpose of this study was to compare gene expression in omental adipose tissue from obese prepubertal and normal weight children. We selected 5 obese (BMI adjusted for age and sex z score >2) and 6 normal weight children. RNA was extracted from omental adipose tissue biopsies and cRNA was hybridizated on the human genome U133 Plus 2.0 Arrays (Affymetrix). Microarray experiments were performed for each sample, and selected group of gene expression values were confirmed with real-time RT-PCR in 10 obese and 10 normal weigth prepubertal children. 1276 genes were found to be differentially expressed at P<0.05. Of those differential genes, 201 were upregulated (Fc>2) and 42 were downregulated (Fc<-2). Genes involved in metabolic and signalling pathways were altered in childhood obesity.
Genome-wide expression in visceral adipose tissue from obese prepubertal children.
Sex, Age, Specimen part
View SamplesGene expression analysis in hLECs treated with gain of function or loss of function of MDK in human melanoma cells. Overall design: Biological triplicates of hLEC treated for 3 days with EGM-2 MV conditioned media of melanoma cells. Cell line SK-Mel-147 KD for MDK (shMDK) and its corresponding control (shCtrl (LoF) and WM164 cell line overexpressing MDK (MDK) or an empty vector (NEG) (GoF) were used to produce the conditioned media.
Whole-body imaging of lymphovascular niches identifies pre-metastatic roles of midkine.
Specimen part, Subject
View SamplesWe have found the existence of a Bmi1+ population in the adult heart contributing to the organ low-rate turnover and repair with the generation of new cardiomyocytes. We show that the Bmi1+ population is a sub-population of the cardiac Sca-1+ progenitor cells. We have analyzed the gene profile by deep-sequencing (RNA-Seq) of Bmi1+ and Sca-1+Bmi1- cells in homeostatic heart condition. On the other hand, we have compared gene profile by deep-sequencing (RNA-Seq) of Bmi1+ cells in homeostatic condition versus Bmi1+ cells 5 days after myocardial infarction (MI). Analysis of RNA-Seq data revealed a differential expression signature between both subsets of cardiac stem/progenitors cells in homeostatic condition and also differences between Bmi1+ cells after AMI versus homeostatic condition. Overall design: Examination of gene profile of 2 different cardiac stem /progenitors subsets (Bmi1+ and Sca-1+Bmi1-) co-existing inthe adult heart under steady state. Examination of gene profile of Bmi1+ cardiac stem cells in homeostatic condition versus MI
Age-related oxidative stress confines damage-responsive Bmi1<sup>+</sup> cells to perivascular regions in the murine adult heart.
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