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Myelinogenic Plasticity of Oligodendrocyte Precursor Cells following Spinal Cord Contusion Injury.

The Journal of neuroscience : the official journal of the Society for Neuroscience | 2017

Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping platelet-derived growth factor receptor α (PDGFRα), Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PDGFRα+) produced oligodendrocytes responsible for de novo ensheathment of ∼30% of myelinated spinal axons at injury epicenter 3 months after SCI, demonstrating that these resident cells are a major contributor to oligodendrocyte regeneration. OPCs also produced the majority of myelinating Schwann cells in the injured spinal cord; invasion of peripheral myelinating (P0+) Schwann cells made only a limited contribution. These findings reveal that PDGFRα+ cells perform diverse roles in CNS repair, as multipotential progenitors that generate both classes of myelinating cells. This endogenous repair might be exploited as a therapeutic target for CNS trauma and disease.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to profound functional deficits, though substantial numbers of axons often survive. One possible explanation for these deficits is loss of myelin, creating conduction block at the site of injury. SCI leads to oligodendrocyte death and demyelination, and clinical trials have tested glial transplants to promote myelin repair. However, the degree and duration of myelin loss, and the extent and mechanisms of endogenous repair, have been contentious issues. Here, we use genetic fate mapping to demonstrate that spontaneous myelin repair by endogenous oligodendrocyte precursors is much more robust than previously recognized. These findings are relevant to many types of CNS pathology, raising the possibility that CNS precursors could be manipulated to repair myelin in lieu of glial transplantation.

Pubmed ID: 28760862 RIS Download

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Antibodies used in this publication

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS051509
  • Agency: CIHR, Canada
    Id: MOP-130475

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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Anti-Nerve Growth Factor Receptor (NGFR p75) antibody produced in rabbit (antibody)

RRID:AB_260763

This unknown targets Nerve Growth Factor Receptor (NGFR p75)

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MOUSE ANTI RAT RECA-1 (antibody)

RRID:AB_323297

This monoclonal targets MOUSE ANTI RAT RECA-1

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Recombinant Anti-PDGFR beta antibody [Y92] - C-terminal (antibody)

RRID:AB_777165

This recombinant monoclonal targets PDGF Receptor beta

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Mouse PDGF R alpha Antibody (antibody)

RRID:AB_2236897

This polyclonal targets Mouse PDGF R alpha

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Anti-Nerve Growth Factor Receptor, p75 (antibody)

RRID:AB_11211656

This polyclonal targets Nerve Growth Factor Receptor p75

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Anti-P-Zero Myelin Protein Antibody (antibody)

RRID:AB_2313561

This polyclonal targets Myelin Protein Zero (Pz0)

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Anti-NG2 Chondroitin Sulfate Proteoglycan (antibody)

RRID:AB_11213678

This polyclonal targets NG2 Chondroitin Sulfate Proteoglycan

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RRID:AB_477257

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nestin (2Q178) (antibody)

RRID:AB_784786

This monoclonal targets nestin

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MBP (C-16) (antibody)

RRID:AB_648798

This polyclonal targets MBP

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Anti-Myelin Basic Protein Antibody (antibody)

RRID:AB_2313550

This polyclonal targets Myelin Basic Protein (MBP)

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Anti-Laminin antibody produced in rabbit (antibody)

RRID:AB_477163

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Glut1 (C-20) (antibody)

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This polyclonal targets SLC2A1

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Anti-Green Fluorescent Protein (antibody)

RRID:AB_94936

This monoclonal targets Green Fluorescent Protein

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Anti-GFP (antibody)

RRID:AB_10013361

This monoclonal targets GFP

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GFP-avictoria (antibody)

RRID:AB_303395

This polyclonal targets GFP

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Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

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Monoclonal Anti-Fibronectin antibody produced in mouse (antibody)

RRID:AB_476988

This monoclonal targets Fibronectin antibody produced in mouse

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Caspr antibody (antibody)

RRID:AB_869934

This polyclonal targets Rat Caspr

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Anti-alpha smooth muscle Actin antibody (antibody)

RRID:AB_2223021

This polyclonal targets alpha smooth muscle Actin

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NEW Anti-alpha-Actin (Smooth Muscle), clone EPR5368,Rabbit Monoclonal (antibody)

RRID:AB_11203118

This monoclonal targets NEW alpha-Actin (Smooth Muscle) clone EPR5368Rabbit

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RRID:IMSR_JAX:007669

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B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (organism)

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Mus musculus with name B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J from IMSR.

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STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (organism)

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Mus musculus with name STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.

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SPSS (software resource)

RRID:SCR_002865

Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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ZEISS ZEN Microscopy Software (software resource)

RRID:SCR_013672

User interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.

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B6N.Cg-Tg(Pdgfra-cre/ERT)467Dbe/J (organism)

RRID:IMSR_JAX:018280

Mus musculus with name B6N.Cg-Tg(Pdgfra-cre/ERT)467Dbe/J from IMSR.

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B6.129S4-Pdgfratm11(EGFP)Sor/J (organism)

RRID:IMSR_JAX:007669

Mus musculus with name B6.129S4-Pdgfratm11(EGFP)Sor/J from IMSR.

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STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (organism)

RRID:IMSR_JAX:007576

Mus musculus with name STOCK Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.

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B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (organism)

RRID:IMSR_JAX:006148

Mus musculus with name B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J from IMSR.

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