The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that 50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedbut not normaladult white matter. We report that -catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of -catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
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View SamplesGene expression analysis of 7d-old Arabidopsis seedlings exposed to short term (2 h) hypoxia, long term (9 h) hypoxia, and 1 h reoxygenation after long term (9 h) hypoxia to evaluate the regulation of gene expression at the level of translation.
Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana.
Age
View SamplesWe investigated the effects of diabetes, physical training, and their combination on the gene expression of cardiac muscle. Mice were divided to control (C), training (T), streptozotocin-induced diabetic (D), and diabetic training (DT) groups. Training groups performed 1, 3, or 5 weeks of endurance training on a motor-driven treadmill. Muscle samples from T and DT groups together with respective controls were collected 24 hours after the last training session. Gene expression of cardiac muscles were analyzed using Affymetrix Gene chip MG U74Av2 (Affymetrix , Inc., Santa Clara, CA).
Effects of streptozotocin-induced diabetes and physical training on gene expression of titin-based stretch-sensing complexes in mouse striated muscle.
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View SamplesExperiment protocol:
Effects of streptozotocin-induced diabetes and physical training on gene expression of extracellular matrix proteins in mouse skeletal muscle.
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View SamplesCerebral malaria (CM) is a leading cause of death in the world. Better understanding of the pathogenesis of this disease is critical for the development of novel therapies. In this work, we investigated temporal gene expression profiles in the brains of CM-susceptible and CM-resistant mice during infection with P. Berghia ANKA (PbA).
Expression microarray analysis implicates apoptosis and interferon-responsive mechanisms in susceptibility to experimental cerebral malaria.
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View SamplesTransient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sex, Specimen part
View Samples18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChip Human Gene 2.0 ST Array.
Molecular biomarker candidates of acute kidney injury in zero-hour renal transplant needle biopsies.
Specimen part
View SamplesThe root epidermis of Arabidopsis provides a simple and experimentally useful model for studying the molecular basis of cell fate and differentiation. The goal of this study was to define the transcript changes in the root epidermis of mutants associated with root epidermis cell specification, including mutants that lack a visible phenotypic alteration (try, egl3, myb23, and ttg2). Transcript levels were assessed by purifying populations of root epidermal cells using fluorescence-based cell-sorting with the WER::GFP transgene. These microarray results were used to compare the effects of single and double mutants on the gene regulatory network that controls root epidermal cell fate and differentiation in Arabidopsis.
Tissue-specific profiling reveals transcriptome alterations in Arabidopsis mutants lacking morphological phenotypes.
Specimen part
View SamplesEffects of hyperglycaemia and genetic background differences on renal gene expression
Comparative analysis of methods for gene transcription profiling data derived from different microarray technologies in rat and mouse models of diabetes.
Sex, Age, Specimen part, Disease, Subject
View SamplesAim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined.
Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial.
Specimen part, Treatment
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