Dynamic gene expression in Schwann cell for regulating myelination
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ABSTRACT:
PROVIDER: PRJNA685041 | ENA |
REPOSITORIES: ENA
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Project description:To obtain the dynamic gene expression of myelinating Schwann cells, we have employed gene expression profiling microarray as a discovery platform to analyze the gene expression of Schwann cells in different stages of myelination in an DRG neuron and SC co-culture myelinating model. Rat Schwann cells and dorsal root ganglion (DRG) neurons were cocultured and induced myelination in DMEM medium containing 15% FBS, 50 ng/ml NGF and 50 μg/ml L-ascorbic acid for 21d. During the co-cultivation, myelinating SCs at different stages dissected by Laser microdissection (LMD) in myelination model (i.e. co-culture 1d, 3d, 7d, 14d, 21d), the Schwann cells without co-culture as control samples (i.e. co-culture 0d). The results from Euclidean distance matrix, principal component analysis, and hierarchical clustering indicated that 2 nodal transitions in temporal gene expressions could segregate 3 distinct transcriptional phases within the period of DRG/SC co-culture 21 days. The 3 phases were designated as “premyelination”, “myelination”, and “mature phase”, respectively, by referring to morphological observation of post co-culture changes and gene ontology (GO) analysis.
2022-09-21 | GSE163132 | GEO
Project description:Myelination is essential for nervous system function. Schwann cells interact with neurons and with the basal lamina to sort and myelinate axons, using known receptors and signaling pathways. In contrast, the transcriptional control of axonal sorting and the role of mechano-transduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. Here, we describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice we show that Taz is required in Schwann cells for radial sorting and myelination. Yap is redundant with Taz as ablation of both Yap and Taz abolishes radial sorting. Yap/Taz regulate Schwann cell proliferation and transcription of basal lamina receptors, both necessary for proper radial sorting of axons, and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.
2016-06-06 | GSE79115 | GEO
Project description:The myelin sheaths that surround the thick axons of the peripheral nervous system are produced by the highly specialized Schwann cells. Differentiation of Schwann cells and myelination occur in discrete steps. Each of these requires coordinated expression of specific proteins in a precise sequence, yet the regulatory mechanisms controlling protein expression during these events are incompletely understood. Here we report that Schwann cell-specific ablation of the enzyme Dicer1, which is required for the production of small non-coding regulatory microRNAs, fully arrests Schwann cell differentiation, resulting in early postnatal lethality. Dicer-/- Schwann cells had lost their ability to myelinate, yet were still capable of sorting axons. Both cell death and, paradoxically, proliferation of immature Schwann cells was vastly enhanced, suggesting that their terminal differentiation is triggered by growth-arresting regulatory microRNAs. Using microRNA microarrays, we identified 16 miRNAs that are upregulated upon myelination and whose expression is controlled by Dicer in Schwann cells. This set of microRNAs appears to drive Schwann cell differentiation and myelination of peripheral nerves, thereby fulfilling a crucial function for survival of the organism. Samples representing Schwann cell-specific ablation of the enzyme Dicer1 and wild type controls at developmental stages E17 and P4. Geometric mean-averaged data linked below as supplementary file.
2010-12-01 | E-GEOD-22023 | biostudies-arrayexpress
Project description:The myelin sheaths that surround the thick axons of the peripheral nervous system are produced by the highly specialized Schwann cells. Differentiation of Schwann cells and myelination occur in discrete steps. Each of these requires coordinated expression of specific proteins in a precise sequence, yet the regulatory mechanisms controlling protein expression during these events are incompletely understood. Here we report that Schwann cell-specific ablation of the enzyme Dicer1, which is required for the production of small non-coding regulatory microRNAs, fully arrests Schwann cell differentiation, resulting in early postnatal lethality. Dicer-/- Schwann cells had lost their ability to myelinate, yet were still capable of sorting axons. Both cell death and, paradoxically, proliferation of immature Schwann cells was vastly enhanced, suggesting that their terminal differentiation is triggered by growth-arresting regulatory microRNAs. Using microRNA microarrays, we identified 16 miRNAs that are upregulated upon myelination and whose expression is controlled by Dicer in Schwann cells. This set of microRNAs appears to drive Schwann cell differentiation and myelination of peripheral nerves, thereby fulfilling a crucial function for survival of the organism.
2010-12-01 | GSE22023 | GEO
Project description:Axonal myelination is essential for neuronal function and health. In peripheral nerves, deficient myelination is responsible for the morbidity of various forms of inherited or acquired neuropathies, including Charcot-Marie-Tooth disease and diabetic neuropathy. Decades of research have uncovered a complex transcriptional and post-transcriptional program that co-ordinates the formation and maintenance of the myelin sheath. In contrast, much less is known about the functional role of post-translational modification (PTM) of proteins in this remarkable biogenic process. Neddylation, a PTM that involves the conjugation of the ubiquitin-like protein Nedd8 to protein targets, has recently emerged as a central and versatile regulator of many cellular processes, including gene transcription, metabolism, and cellular differentiation. In this study, we show that genetic and pharmacological inhibition of neddylation in vivo in developing Schwann cells lead to striking nerve defects that exhibit the classical hallmarks of a severe neuropathy, including gait abnormalities, muscle weakness, and hindlimb clasping, ultimately leading to early death. The mutant mice lack peripheral myelin and develop secondary axonal loss, and we demonstrate, at the mechanistic level, that neddylation regulates multiple critical myelination-related pathways. Together, our findings identify neddylation as a central regulatory hub of control of peripheral myelination and delineate the potential pathogenetic mechanisms in inherited human PNS disorders, characterized by mutations in genes related to the neddylation pathway.
2024-06-16 | PXD043917 | Pride
Project description:Using pangenomic cDNA microarrays and qPCR techniques, we identified the genes regulated by calcitriol (1,25 (OH)D3, 10 nM) in dorsal root ganglia and/or Schwann cells. After 24 hours of calcitriol supplementation, we found a modified expression of many genes involved in axogenesis and myelination.
2012-04-07 | E-MEXP-3491 | biostudies-arrayexpress
Project description:Myelin sheath formation in the peripheral nervous system is a complex event resulting from spatially and temporally regulated reciprocal interactions between the neuron and myelin-forming Schwann cells. Although many of the components of the sheath have been identified and well-characterized, our knowledge of the dynamic cellular and molecular processes and of the protein functional networks that participate in its formation is still weak. This paper describes a robust approach, combining transcriptomics, proteomics and immunocytochemistry analyses of myelinating dorsal root ganglion cultures derived from C57BL/6J mice, which can be exploited to identify protein networks, and their constituent modules, involved in peripheral nerve myelin formation. The approach allows distinguishing clear, reproducible and predictable differences between the structural properties of the cultures and their genome-wide and proteomic expression profiles at different stages of the myelination process. The expression profiles of selected neuronal and Schwann cell genes and proteins in the cultures reflect those observed in vivo, and the structural and ultrastructural properties and myelination schedule of the cultures closely resemble those observed in peripheral nerves in situ. The approach provides a unique and powerful tool to study comprehensive transcriptome and proteomic changes taking place simultaneously in Schwann cells and neurons during PNS myelination.
2015-08-16 | GSE60345 | GEO
Project description:DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe. Axonal myelination by Schwann cells in the peripheral nervous system is essential for rapid saltatory impulse conduction, and malformation or destruction of myelin sheaths can lead to severe motor and sensory disabilities (peripheral neuropathies). Using high-resolution genome-scale methylome maps, we found that DNA methylation could play a critical role in the generation of myelinated Schwann cells. This process was accompanied by a global DNA demethylation at most genomic elements. Notably, demethylation at gene-regulatory regions was associated with activation of critical myelination-specific genes. Furthermore, we found an aberrant DNA methylation pattern in a mouse model of diabetic neuropathy, which could be involved in the pathogenesis of the disease. Importantly, we found that these methylation patterns in both situations could be regulated by levels of S-adenosylmethionine (SAMe), the principal biological methyl donor. Together with recent studies on the influence of SAMe on histone methylation in diverse biological processes, we conclude that the methylation landscape of cells could be critically dependent on levels of SAMe. These provide a mechanistic link between metabolism and gene regulatory networks in normal and pathological situations. Sciatic nerves from post natal day 90 GNMT (wt and KO) mice of either sex were dissected and pooled together, 2 replicates per sample group.
2014-01-27 | E-GEOD-45701 | biostudies-arrayexpress
Project description:DNA methylation is a key epigenetic regulator of mammalian embryogenesis and somatic cell differentiation. Using high-resolution genome-scale maps of methylation patterns, we show that the formation of myelin in the peripheral nervous system, proceeds with progressive DNA demethylation, which coincides with an upregulation of critical genes of the myelination process. More importantly, we found that, in addition to expression of DNA methyltransferases and demethylases, the levels of S-adenosylmethionine (SAMe), the principal biological methyl donor, could also play a critical role in regulating DNA methylation during myelination and in the pathogenesis of diabetic neuropathy. In summary, this study provides compelling evidence that SAMe levels need to be tightly controlled to prevent aberrant DNA methylation patterns, and together with recently published studies on the influence of SAMe on histone methylation in cancer and embryonic stem cell differentiation show that in diverse biological processes, the methylome, and consequently gene expression patterns, are critically dependent on levels of SAMe. Axonal myelination by Schwann cells in the peripheral nervous system is essential for rapid saltatory impulse conduction, and malformation or destruction of myelin sheaths can lead to severe motor and sensory disabilities (peripheral neuropathies). Using high-resolution genome-scale methylome maps, we found that DNA methylation could play a critical role in the generation of myelinated Schwann cells. This process was accompanied by a global DNA demethylation at most genomic elements. Notably, demethylation at gene-regulatory regions was associated with activation of critical myelination-specific genes. Furthermore, we found an aberrant DNA methylation pattern in a mouse model of diabetic neuropathy, which could be involved in the pathogenesis of the disease. Importantly, we found that these methylation patterns in both situations could be regulated by levels of S-adenosylmethionine (SAMe), the principal biological methyl donor. Together with recent studies on the influence of SAMe on histone methylation in diverse biological processes, we conclude that the methylation landscape of cells could be critically dependent on levels of SAMe. These provide a mechanistic link between metabolism and gene regulatory networks in normal and pathological situations. Sciatic nerves from C57Bl6J mice of either sex, were dissected and pooled together at different developmental stages, 3 replicates per sample group.
2014-01-27 | E-GEOD-45700 | biostudies-arrayexpress
Project description:Disorders that disrupt myelin during development or in adulthood, such as multiple sclerosis and peripheral neuropathies, lead to severe pathologies, illustrating myelin’s crucial role in normal neural functioning. However, although our understanding of Schwann cell and oligodendrocyte biology is increasing, the signals that emanate from axons and regulate myelination remain largely unknown. To identify the core components of the myelination process, we adopted a microarray analysis approach combined with laser capture microdissection of spinal motoneurons (MNs) during the myelinogenic phase of development.
2020-07-09 | GSE133744 | GEO