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Featured ArticleArticles, Development/Plasticity/Repair

A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia

Martha S. Windrem, Steven J. Schanz, Carolyn Morrow, Jared Munir, Devin Chandler-Militello, Su Wang and Steven A. Goldman
Journal of Neuroscience 26 November 2014, 34 (48) 16153-16161; DOI: https://doi.org/10.1523/JNEUROSCI.1510-14.2014
Martha S. Windrem
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
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Steven J. Schanz
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
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Carolyn Morrow
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
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Jared Munir
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
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Devin Chandler-Militello
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
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Su Wang
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
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Steven A. Goldman
1Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and
2Center for Basic and Translational Neuroscience, University of Copenhagen Faculty of Medicine, 2200 Copenhagen N, Denmark
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Abstract

Neonatally transplanted human glial progenitor cells (hGPCs) densely engraft and myelinate the hypomyelinated shiverer mouse. We found that, in hGPC-xenografted mice, the human donor cells continue to expand throughout the forebrain, systematically replacing the host murine glia. The differentiation of the donor cells is influenced by the host environment, such that more donor cells differentiated as oligodendrocytes in the hypomyelinated shiverer brain than in myelin wild-types, in which hGPCs were more likely to remain as progenitors. Yet in each recipient, both the number and relative proportion of mouse GPCs fell as a function of time, concomitant with the mitotic expansion and spread of donor hGPCs. By a year after neonatal xenograft, the forebrain GPC populations of implanted mice were largely, and often entirely, of human origin. Thus, neonatally implanted hGPCs outcompeted and ultimately replaced the host population of mouse GPCs, ultimately generating mice with a humanized glial progenitor population. These human glial chimeric mice should permit us to define the specific contributions of glia to a broad variety of neurological disorders, using human cells in vivo.

  • cell transplant
  • chimera
  • demyelinating disease
  • glial progenitor
  • neural stem cell
  • oligodendrocytic progenitor
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The Journal of Neuroscience: 34 (48)
Journal of Neuroscience
Vol. 34, Issue 48
26 Nov 2014
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A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia
Martha S. Windrem, Steven J. Schanz, Carolyn Morrow, Jared Munir, Devin Chandler-Militello, Su Wang, Steven A. Goldman
Journal of Neuroscience 26 November 2014, 34 (48) 16153-16161; DOI: 10.1523/JNEUROSCI.1510-14.2014

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A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia
Martha S. Windrem, Steven J. Schanz, Carolyn Morrow, Jared Munir, Devin Chandler-Militello, Su Wang, Steven A. Goldman
Journal of Neuroscience 26 November 2014, 34 (48) 16153-16161; DOI: 10.1523/JNEUROSCI.1510-14.2014
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Keywords

  • cell transplant
  • chimera
  • demyelinating disease
  • glial progenitor
  • neural stem cell
  • oligodendrocytic progenitor

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