Glial progenitor cells comprise the most abundant population of progenitor cells in the adult human brain. They are responsible for CNS remyelination, and likely contribute to the astrogliotic response to brain injury and degeneration as well. Adult human GPCs are biased to differentiate as oligodendrocytes and elaborate new myelin, and yet they retain multilineage plasticity, and can give rise to neurons as well as astrocytes and oligodendrocytes once removed from the adult parenchymal environment. GPCs retain strong mechanisms for cell-autonomous self-renewal, and yet both their phenotype and fate may be dictated by their microenvironment. Using the transcriptional profiles of acutely isolated GPCs, we have begun to understand the operative ligand-receptor interactions involved in these processes, and have identified several key signaling pathways by which adult human GPCs may be reliably instructed to either oligodendrocytic or astrocytic fate. In addition, we have noted significant differences between the expressed genes and dominant signaling pathways of fetal and adult human GPCs, as well as between rodent and human GPCs. The latter data in particular call into question therapeutic strategies predicated solely upon data obtained using rodents, while perhaps highlighting the extent to which evolution has been attended by the phylogenetic modification of glial phenotype and function.
Fate determination of adult human glial progenitor cells.
Specimen part, Subject
View SamplesGlial progenitor cells (GPCs) pervade the human brain. These cells express gangliosides recognized by MAb A2B5, and some but not all can generate oligodendrocytes. Since some A2B5+ GPCs express PDGFa receptor (PDGFRa), which is critical to oligodendrocyte development, we asked if PDGFRa-directed sorting might isolate oligodendrocyte-competent progenitors. We used FACS to sort PDGFRa+ cells from the second trimester fetal human forebrain, based on expression of the PDGFRa epitope CD140a. CD140a+ cells could be maintained as mitotic progenitors that could be instructed to either oligodendrocyte or astrocyte phenotype. Transplanted CD140a+ cells robustly myelinated the hypomyelinated shiverer mouse brain. Microarray confirmed that CD140a+ cells differentially expressed PDGFRA, NG2, OLIG1/2, NKX2.2 and SOX2. Some expressed CD9, thereby defining a CD140a+/CD9+ fraction of oligodendrocyte-biased progenitors. CD140a+ cells differentially expressed genes of the PTN-PTPRZ1, wnt, notch and BMP pathways, suggesting the interaction of self-renewal and fate-restricting pathways in these cells, while identifying targets for their mobilization and instruction.
CD140a identifies a population of highly myelinogenic, migration-competent and efficiently engrafting human oligodendrocyte progenitor cells.
Specimen part
View SamplesIn order to test the hypothesis that fibroblasts from different tissues are phenotypically distinct from one another, we have subjected tendon, skin and corneal fibroblasts of fetal mouse to mechanical stimulation by fluid flow and analyzed the transcriptional responses of the cells using Affymetrix MOE430 chip set containing two arrays MOE430A and MOE430B.
Phenotypic responses to mechanical stress in fibroblasts from tendon, cornea and skin.
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View SamplesPhysiological effects of carbon dioxide and impact on genome-wide transcript profiles were analysed in chemostat cultures of Saccharomyces cerevisiae. In anaerobic, glucose-limited chemostat cultures grown at atmospheric pressure, cultivation under CO2-saturated conditions had only a marginal (<10%) impact on the biomass yield. Conversely, a 25% decrease of the biomass yield was found in aerobic, glucose-limited chemostat cultures aerated with a mixture of 79% CO2 and 21% O2. This observation indicated that respiratory metabolism is more sensitive to CO2 than fermentative metabolism. Consistent with the more pronounced physiological effects of CO2 in respiratory cultures, the number of CO2-responsive transcripts was higher in aerobic cultures than in anaerobic cultures. Many genes involved in mitochondrial functions showed a transcriptional response to elevated CO2 concentrations. This is consistent with an uncoupling effect of CO2 and/or intracellular bicarbonate on the mitochondrial inner membrane. Other transcripts that showed a significant transcriptional response to elevated CO2 included NCE103 (probably encoding carbonic anhydrase), PCK1 (encoding PEP carboxykinase) and members of the IMD gene family (encoding isozymes of inosine monophosphate dehydrogenase
Physiological and genome-wide transcriptional responses of Saccharomyces cerevisiae to high carbon dioxide concentrations.
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View SamplesProlonged cultivation (>25 generations) of Saccharomyces cerevisiae in aerobic, maltose-limited chemostat cultures led to profound physiological changes. Maltose hypersensitivity was observed when cells from prolonged cultivations were suddenly exposed to excess maltose. This substrate hypersensitivity was evident from massive cell lysis and loss of viability. During prolonged cultivation at a fixed specific growth rate, the affinity for the growth-limiting nutrient (i.e., maltose) increased, as evident from a decreasing residual maltose concentration. Furthermore, the capacity of maltose-dependent proton uptake increased up to 2.5-fold during prolonged cultivation. Genome-wide transcriptome analysis showed that the increased maltose transport capacity was not primarily due to increased transcript levels of maltose-permease genes upon prolonged cultivation. We propose that selection for improved substrate affinity (ratio of maximum substrate consumption rate and substrate saturation constant) in maltose-limited cultures leads to selection for cells with an increased capacity for maltose uptake. At the same time, the accumulative nature of maltose-proton symport in S. cerevisiae leads to unrestricted uptake when maltose-adapted cells are exposed to a substrate excess. These changes were retained after isolation of individual cell lines from the chemostat cultures and nonselective cultivation, indicating that mutations were involved. The observed trade-off between substrate affinity and substrate tolerance may be relevant for metabolic engineering and strain selection for utilization of substrates that are taken up by proton symport.
Prolonged maltose-limited cultivation of Saccharomyces cerevisiae selects for cells with improved maltose affinity and hypersensitivity.
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View SamplesMaggot ES is known to induce wound healing in vivo to improve chronic wound repair. The effects have been studies at the protein and molecular level but never before at the transcriptional level.
The transcriptional responses of cultured wound cells to the excretions and secretions of medicinal Lucilia sericata larvae.
Specimen part, Cell line
View SamplesThe capacity of respiring cultures of Saccharomyces cerevisiae to instantaneously switch to fast alcoholic fermentation upon a transfer to anaerobic sugar-excess conditions is a key characteristic of Saccharomyces cerevisiae in many of its industrial applications. This transition was studied by exposing aerobic glucose-limited chemostat cultures grown at a low specific growth rate to two simultaneous perturbations: oxygen depletion and relief of glucose limitation. This shift towards fully fermentative conditions caused a massive transcriptional response, where one third of all genes within the genome were transcribed differentially. During the first 30 min, most of these changes were driven by relief from glucose limitation. An anaerobic induction response was only observed after the initial response to glucose excess. By comparing this study with public datasets representing dynamic and steady conditions, 14 up-regulated and 11 down-regulated genes were determined to be anaerobiosis specific and can therefore be use as signature transcripts for anaerobicity under dynamic as well as under steady state conditions
New insights into the Saccharomyces cerevisiae fermentation switch: dynamic transcriptional response to anaerobicity and glucose-excess.
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View SamplesTo identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone (Crh), the GABA transporter (Slc6a1), and prodynorphin (Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G15 coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr, and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Further, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.
Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum.
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View SamplesAddition of 3 new arrays made from carbon limited chemostat of CENPK113-7D and 3 new arrays made from aerobic carbon limited chemostat of CENPK113-7D Complmentary data to the data of the serie GSE1723.
Exploiting combinatorial cultivation conditions to infer transcriptional regulation.
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View SamplesThe goal of this study was to study this interaction by analyzing genome-wide transcriptional responses to four different nutrient-limitation regimes under aerobic and anaerobic conditions in chemostat cultures of S. cerevisiae. This two-dimensional approach resulted in a new, robust set of anaerobic and aerobic signature transcripts for S. cerevisiae, as well as to a refinement of previous reports on nutrient-responsive genes. Moreover, the identification of genes regulated both by nutrient and oxygen availability provided new insight in cross-regulated network and hierarchy in the control of gene expression.
Two-dimensional transcriptome analysis in chemostat cultures. Combinatorial effects of oxygen availability and macronutrient limitation in Saccharomyces cerevisiae.
No sample metadata fields
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