A competitive advantage by neonatally engrafted human glial progenitors yields mice whose brains are chimeric for human glia

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

SN - 0270-6474

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

IS - 48

ER -