Cells constantly adapt to changes in their environment. In the majority of cases, the environment shifts between conditions that were previously encountered during the course of evolution, thus enabling evolutionary-programmed responses. In rare cases, however, cells may encounter a new environment to which a novel response is required. To characterize the first steps in adaptation to a novel condition, we studied budding yeast growth on xylulose, a sugar that is very rarely found in the wild. We previously reported that growth on xylulose induces the expression of amino-acid biosynthesis genes, in multiple natural yeast isolates. This induction occurs despite the presence of amino acids in the growth medium and is a unique response to xylulose, not triggered by any of the naturally available carbon sources tested. Propagating these strains for ~300 generations on xylulose significantly improved their growth rate. Notably, the most significant change in gene expression was the loss of amino acid biosynthesis gene induction. Furthermore, the reduction in amino-acid biosynthesis gene expression on xylulose was strongly correlated with the improvement in growth rate, suggesting that internal depletion of amino-acids presented the major bottleneck limiting growth in xylulose. We discuss the possible implications of our results for explaining how cells maintain the balance between supply and demand of amino acids during growth in evolutionary 'familiar' vs. 'novel' conditions. Overall design: mRNA profiles of 12 wt S. cerevisiae strains grown on either YPD or YP-xylulose, before and after 300 generations evolution on YP-xylulose
Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source.
Cell line, Subject
View SamplesWe carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sex, Age, Specimen part
View SamplesWe conducted a set of lab-evolution experiments in yeast and followed the long-term dynamics of aneuploidy under diverse conditions including heat shock and high PH.
Chromosomal duplication is a transient evolutionary solution to stress.
No sample metadata fields
View SamplesWe purified by magnet assisted cell sorting microglial cells from brains of adult Rab7 null mutant, aged mice and respective controls, isolated total RNA and performed RNAseq to determine the transciptome profiles. Overall design: Examination of transcriptomes of Rab7 null mutants and control (2 replicates each) and aged mice and young controls (3 replicates each)
Age-related myelin degradation burdens the clearance function of microglia during aging.
Age, Specimen part, Cell line, Subject
View SamplesInterleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome wide association studies and experimental animal models point at a central role of the IL-10 axis in Inflammatory Bowel Diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10R) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1hi-expressingmacrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages, but resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning factor in the colon and define intestinal CX3CR1hi macrophages as a decisive factor that determines gut health or inflammation.
Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis.
Age, Specimen part
View Samples2 types of dendritic cells (DCs) can be generated in vitro in the presence of Flt3-L: CD4+ equivalent CD24- DCs and CD8+ equivalent CD24+ DCs. miR-142-/- mice show a severe defect in the generation of CD4+ equivalent CD24- DCs. To understand the underlying mechanism, RNA expression was analyzed by Affymetrix microarray from the 2 in vitro subtypes of DCs derived from miR-142+/+ and miR-142-/- bone marrow cells.
Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis.
Specimen part
View SamplesGene expression profile of squamous lung cancer cells are used to identify genes that are differentially regulated.
Interactome-transcriptome analysis reveals the high centrality of genes differentially expressed in lung cancer tissues.
No sample metadata fields
View SamplesWe show that aneuploidy is common in wild isolates of yeast, which are inherently tolerant to chromosome amplification and down-regulate expression at 40% of amplified genes. To dissect the mechanism of this dosage response, we generated isogenic strain panels in which diploid cells carried either two, three, or four copies of the affected chromosomes. Using a mixture of linear regression (MLR) model to classify genes, we find that expression is actively down regulated in proportion to increased gene copy at up to 30% of genes. Genes subject to dosage control are under higher expression constraint – but show elevated rates of gene amplification – in wild populations, suggesting that dosage compensation buffers copy number variation (CNV) at toxic genes Overall design: RNA-seq and transcriptome analysis of S. cerevisiae natural isolates having aneuploidy. Technical triplicate was performed for isogenic diploid strains having 2, 3 and 4 copies of a given chromosome (strain panels), while technical duplicate or singulate was performed on all other aneuploids.
Dosage compensation can buffer copy-number variation in wild yeast.
Subject
View SamplesThe ERK family of MAP kinase plays a critical role in growth factor-stimulated cell cycle progression from G0/G1 to S phase. But, how sustained activation of ERK promotes G1 progression has remained unclear. Here, our systematic analysis on the temporal program of ERK-dependent gene expression shows that sustained activation of ERK is required for induction and maintenance of the decreased expression levels of a set of genes. Moreover, our cell biological analysis reveals that these ERK-dependent downregulated genes have the ability to block S phase entry. Cessation of ERK activation at mid or late G1 leads to a rapid increase of these anti-proliferative genes and results in the inhibition of S phase entry. These findings uncover an important mechanism by which the duration of ERK activation regulates cell cycle progression through dynamic changes in gene expression, and identify novel ERK target genes crucial for the regulation of cell cycle progression.
Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
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