title: A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia.
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.
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and martha_windrem@urmc.rochester.edu steven_goldman@urmc.rochester.edu.
authors.forename: Martha S
authors.initials: MS
authors.lastname: Windrem
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schanz
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Morrow
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and.
authors.forename: Jared
authors.initials: J
authors.lastname: Munir
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and.
authors.forename: Devin
authors.initials: D
authors.lastname: Chandler-Militello
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and.
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.affiliation: Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York 14642, and Center for Basic and Translational Neuroscience, University of Copenhagen Faculty of Medicine, 2200 Copenhagen N, Denmark martha_windrem@urmc.rochester.edu steven_goldman@urmc.rochester.edu.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Goldman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002678:Chimera / Q000502:physiology*; D005260:Female; D053686:Fetal Stem Cells / Q000502:physiology* / Q000637:transplantation*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000502:physiology* / Q000637:transplantation*; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods
keywords: cell transplant; chimera; demyelinating disease; glial progenitor; neural stem cell; oligodendrocytic progenitor