Diminishing potential to replace damaged tissues is a hallmark for ageing of somatic stem cells, but the mechanisms leading to ageing remain elusive. We present a proteome-wide atlas of age-associated alterations in human haematopoietic stem and progenitor cells (HPCs) along with five other cell types that constitute the bone marrow niche. For each, the abundance of a large fraction of the ~12,000 proteins identified was assessed in a cohort of healthy human subjects from different age. As the HPCs became older, pathways in central carbon metabolism exhibited features reminiscent of the Warburg effect where glycolytic intermediates are rerouted towards anabolism. Simultaneously, altered abundance of early regulators of HPC differentiation revealed a reduced functionality and a bias towards myeloid differentiation at the expense of lymphoid development. Ageing caused significant alterations in the bone marrow niche too, such as functionality of the pathways involved in HPC homing and lineage differentiation. The data represents a valuable resource for further in-depth mechanistic analyses, and for validation of knowledge gained from animal models. Overall design: RNA-seq samples extracted from human bone marrow, from 6 cell populations (HPC, LYM, MON, ERP, GRA, MSC). Technical replicates are included for each donor and cell type. Technical replicates were produced by making independent libraries from the same RNA.
Glycogen accumulation, central carbon metabolism, and aging of hematopoietic stem and progenitor cells.
Sex, Age, Specimen part, Subject
View SamplesThis study was performed to understand what controls the aggressivity of the pancreatic infiltrate during type-I diabetes development. We used the BDC2.5 transgenic mouse model. Samples were obtained at the age of onset of insultis. Depending on their genetic background, mice transgenic for the BDC2.5 T cell receptor present very different forms of insulitis. The NOD genetic background leads to a benign insulitis whereas the C57Bl/6-H2g7/g7 leads to an aggressive insulitis. We first studied how antigen-specific T cells are affected by these differences by obtaining the transcriptional profiles of BDC2.5 T cells from pancreas and pancreatic lymph nodes. We also compared the gene expression profiles of the entire leukocyte population present in the pancreatic lesion.
Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity.
Age, Specimen part
View SamplesThe development of high-throughput genomic technologies has revealed that a large fraction of the genomes of eukaryotes is associated with the expression of noncoding RNAs. One class of noncoding RNA, the cis-natural antisense transcripts (cis-NATs), are particularly interesting as they are at least partially complementary to the protein-coding mRNAs. Although most studies described cis-NATs involved in the regulation of transcription, a few reports have shown recently that cis-NATs can also regulate translation of the cognate sense coding genes in plants and mammals. In order to identify novel examples of translation regulator cis-NATs in Arabidopsis thaliana, we designed a high-throughput experiment based on polysome profiling and RNA-sequencing. Expression of cis-NATs and translation efficiency of the cognate coding mRNAs were measured in roots and shoots in response to various conditions, including phosphate deficiency and treatment with phytohormones. We identified several promising candidates, and validated a few of them experimentally, in Arabidopsis thaliana transgenic lines over-expressing in trans the translation regulator candidate cis-NATs. Overall design: total RNA and polysomal RNA was sequenced from Arabidopsis thaliana whole seedlings grown in high or low pohsphate content, or from roots or shoots from seedlings treated or not with different phytohormones (Ctrl, IAA, ABA,MeJA and ACC). 3 biological replicates were analyzed for each of the 12 experimental conditions.
Prediction of regulatory long intergenic non-coding RNAs acting in trans through base-pairing interactions.
Specimen part, Treatment, Subject
View SamplesT2 progenies of two transgenic lines overexpressing ERF transcription factor WIN1 were grown on soil in parallel under identical conditions. mRNA was extracted from pooled leaves from multiple plants of each line for the microarray experiement.
WIN1, a transcriptional activator of epidermal wax accumulation in Arabidopsis.
No sample metadata fields
View SamplesThe molecular mechanism(s) leading to Purkinje neuron loss in the neurodegenerative disorder Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) are limited by the complex morphology of this cell type. Purkinje neurons are notoriously difficult to isolate and maintain in culture presenting considerable difficultly to identify molecular changes in response to riboCGG repeat-containing mRNA that induces neurotoxicity in FXTAS. Several studies have uncovered a number of RNA binding proteins involved in translation that aberrantly interact with the toxic RNA; however, whether these interactions alter the translational profile of cells has not been investigated. Here we employ bacTRAP translational profiling to demonstrate that Purkinje neurons ectopically expressing 90 CGG repeats exhibit a dramatic change in their translational profile even prior to the onset of riboCGG-induced phenotypes. This approach identified nearly 500 transcripts that are differentially associated with ribosomes in r(CGG)90-expressing mice. Functional annotation cluster analysis revealed broad ontologies enriched in the r(CGG)90 list, including RNA binding and response to stress. Intriguingly, a transcript for the Tardbp gene, implicated in a number of other neurodegenerative disorders, exhibits altered association with ribosomes in the presence of r(CGG)90 repeats. We therefore tested and showed that reduced association of Tardbp mRNA with the ribosomes results in a loss of TDP-43 protein expression in r(CGG)90expressing Purkinje neurons. Furthermore, we showed that TDP-43 could modulate the rCGG repeat-mediated toxicity in a Drosophila model that we developed previously. These findings together suggest translational dysregulation may be an underlying mechanism of riboCGG-induced neurotoxicity and provide insight into the pathogenicity of FXTASBAC-trap studies of Purkinje cels in normal and mutant mice
CGG repeats in RNA modulate expression of TDP-43 in mouse and fly models of fragile X tremor ataxia syndrome.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Performance comparison of two microarray platforms to assess differential gene expression in human monocyte and macrophage cells.
Sex, Age, Specimen part
View SamplesThis study provides the dectin-1 and NFAT responsive genes for 2h and 4h of curdlan treatment.
NFATc2 mediates epigenetic modification of dendritic cell cytokine and chemokine responses to dectin-1 stimulation.
Specimen part
View SamplesDendritic cells (DCs) are crucial for sensing pathogens and triggering immune response. GM-CSF myeloid dendritic cells (GM-DCs) secrete several cytokines including IL-2 upon activation by pathogen associated molecular pattern (PAMP) ligands. DC IL-2 has been shown to be important for innate and adaptive immune responses, however its importance in DC physiology has never been demonstrated. This is due to ambiguity in expression of the CD122 subunit of the IL-2 trimeric receptor complex crucial for signaling. We show here that autocrine IL-2 signaling is functional in GM-DCs in early time window of stimulation with PAMPs. IL-2 signaling selectively activates the JAK/STAT5 pathway by assembling holo-receptor complexs at the cell surface. Autocrine IL-2 signaling inhibits survival of PAMP matured GM-DCs which is crucial for maintaining immune tolerance and preventing autoimmunity. Our findings suggest immune regulation by a novel autocrine signaling pathway that can potentially be exploited in DC immunotherapy.
Dendritic cell derived IL-2 inhibits survival of terminally mature cells via an autocrine signaling pathway.
Specimen part
View SamplesThe present study was conducted to compare the ability of Affymetrix and Illumina microarray technologies to characterize the differential gene expression profiles of human monocytes and monocyte-derived-macrophages.
Performance comparison of two microarray platforms to assess differential gene expression in human monocyte and macrophage cells.
Sex, Age, Specimen part
View SamplesCharacterization of colon CD11chigh/MHCII+ myeloid cell subsets
Intestinal CD103(+)CD11b(-) dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells.
No sample metadata fields
View Samples