A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia
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A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia. / Windrem, Martha S; Schanz, Steven J; Morrow, Carolyn; Munir, Jared; Chandler-Militello, Devin; Wang, Su; Goldman, Steven A.
In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 34, No. 48, 26.11.2014, p. 16153-61.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia
AU - Windrem, Martha S
AU - Schanz, Steven J
AU - Morrow, Carolyn
AU - Munir, Jared
AU - Chandler-Militello, Devin
AU - Wang, Su
AU - Goldman, Steven A
N1 - Copyright © 2014 the authors 0270-6474/14/3416153-09$15.00/0.
PY - 2014/11/26
Y1 - 2014/11/26
N2 - 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.
AB - 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.
KW - Animals
KW - Animals, Newborn
KW - Chimera
KW - Female
KW - Fetal Stem Cells
KW - Humans
KW - Male
KW - Mice
KW - Mice, Transgenic
KW - Neuroglia
KW - Prosencephalon
KW - Stem Cell Transplantation
U2 - 10.1523/JNEUROSCI.1510-14.2014
DO - 10.1523/JNEUROSCI.1510-14.2014
M3 - Journal article
C2 - 25429155
VL - 34
SP - 16153
EP - 16161
JO - The Journal of neuroscience : the official journal of the Society for Neuroscience
JF - The Journal of neuroscience : the official journal of the Society for Neuroscience
SN - 0270-6474
IS - 48
ER -
ID: 152956021