Demyelination Causes Adult CNS Progenitors to Revert to an Immature State and Express Immune Cues That Support Their Migration
Open Access
- 7 January 2015
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 35 (1), 4-20
- https://doi.org/10.1523/jneurosci.0849-14.2015
Abstract
The declining efficiency of myelin regeneration in individuals with multiple sclerosis has stimulated a search for ways by which it might be therapeutically enhanced. Here we have used gene expression profiling on purified murine oligodendrocyte progenitor cells (OPCs), the remyelinating cells of the adult CNS, to obtain a comprehensive picture of how they become activated after demyelination and how this enables them to contribute to remyelination. We find that adult OPCs have a transcriptome more similar to that of oligodendrocytes than to neonatal OPCs, but revert to a neonatal-like transcriptome when activated. Part of the activation response involves increased expression of two genes of the innate immune system,IL1β andCCL2, which enhance the mobilization of OPCs. Our results add a new dimension to the role of the innate immune system in CNS regeneration, revealing how OPCs themselves contribute to the postinjury inflammatory milieu by producing cytokines that directly enhance their repopulation of areas of demyelination and hence their ability to contribute to remyelination.Keywords
This publication has 43 references indexed in Scilit:
- A Real Time Chemotaxis Assay Unveils Unique Migratory Profiles amongst Different Primary Murine MacrophagesPLOS ONE, 2013
- Activation of Thromboxane A2 Receptor (TP) Increases the Expression of Monocyte Chemoattractant Protein -1 (MCP-1)/Chemokine (C-C motif) Ligand 2 (CCL2) and Recruits Macrophages to Promote Invasion of Lung Cancer CellsPLOS ONE, 2013
- CCL2/MCP-1 modulation of microglial activation and proliferationJournal of Neuroinflammation, 2011
- Axin2 as regulatory and therapeutic target in newborn brain injury and remyelinationNature Neuroscience, 2011
- Myelin Gene Regulatory Factor Is a Critical Transcriptional Regulator Required for CNS MyelinationCell, 2009
- Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNSGenes & Development, 2009
- Neonatal and adult O4+ oligodendrocyte lineage cells display different growth factor responses and different gene expression patternsJournal of Neuroscience Research, 2009
- Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiencyNature Neuroscience, 2008
- A Transcriptome Database for Astrocytes, Neurons, and Oligodendrocytes: A New Resource for Understanding Brain Development and FunctionJournal of Neuroscience, 2008
- Alveolar macrophages lack CCR2 expression and do not migrate to CCL2Journal of Inflammation, 2007