Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination

Emily Grace Baxi, Joseph Debruin, Jing Jin, Hayley J. Strasburger, Matthew D. Smith, Jennifer L. Orthmann-Murphy, Jason T. Schott, Amanda N. Fairchild, Dwight E Bergles, Peter Calabresi

Research output: Contribution to journalArticle

Abstract

The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.

Original languageEnglish (US)
JournalGLIA
DOIs
StateAccepted/In press - 2017

Fingerprint

Cuprizone
Oligodendroglia
Demyelinating Diseases
Stem Cells
Corpus Callosum
Multiple Sclerosis
Cell Differentiation
Platelet-Derived Growth Factor Receptors
Gyrus Cinguli
Myelin Sheath
Atrophy

Keywords

  • Demyelination
  • Gray matter
  • Multiple sclerosis
  • Oligodendrocyte progenitor cells
  • Remyelination

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination. / Baxi, Emily Grace; Debruin, Joseph; Jin, Jing; Strasburger, Hayley J.; Smith, Matthew D.; Orthmann-Murphy, Jennifer L.; Schott, Jason T.; Fairchild, Amanda N.; Bergles, Dwight E; Calabresi, Peter.

In: GLIA, 2017.

Research output: Contribution to journalArticle

Baxi, Emily Grace ; Debruin, Joseph ; Jin, Jing ; Strasburger, Hayley J. ; Smith, Matthew D. ; Orthmann-Murphy, Jennifer L. ; Schott, Jason T. ; Fairchild, Amanda N. ; Bergles, Dwight E ; Calabresi, Peter. / Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination. In: GLIA. 2017.
@article{ebd323e8e7fc4eaeafd02eb5769aa5fc,
title = "Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination",
abstract = "The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.",
keywords = "Demyelination, Gray matter, Multiple sclerosis, Oligodendrocyte progenitor cells, Remyelination",
author = "Baxi, {Emily Grace} and Joseph Debruin and Jing Jin and Strasburger, {Hayley J.} and Smith, {Matthew D.} and Orthmann-Murphy, {Jennifer L.} and Schott, {Jason T.} and Fairchild, {Amanda N.} and Bergles, {Dwight E} and Peter Calabresi",
year = "2017",
doi = "10.1002/glia.23229",
language = "English (US)",
journal = "GLIA",
issn = "0894-1491",
publisher = "John Wiley and Sons Inc.",

}

TY - JOUR

T1 - Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination

AU - Baxi, Emily Grace

AU - Debruin, Joseph

AU - Jin, Jing

AU - Strasburger, Hayley J.

AU - Smith, Matthew D.

AU - Orthmann-Murphy, Jennifer L.

AU - Schott, Jason T.

AU - Fairchild, Amanda N.

AU - Bergles, Dwight E

AU - Calabresi, Peter

PY - 2017

Y1 - 2017

N2 - The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.

AB - The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.

KW - Demyelination

KW - Gray matter

KW - Multiple sclerosis

KW - Oligodendrocyte progenitor cells

KW - Remyelination

UR - http://www.scopus.com/inward/record.url?scp=85030174585&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030174585&partnerID=8YFLogxK

U2 - 10.1002/glia.23229

DO - 10.1002/glia.23229

M3 - Article

C2 - 28940645

AN - SCOPUS:85030174585

JO - GLIA

JF - GLIA

SN - 0894-1491

ER -