A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia
A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia
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DOI：
10.1523/jneurosci.1510-14.2014
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发表时间：
2014-11-26
影响因子：
5.3
通讯作者：
Goldman, Steven A.
中科院分区：
文献类型：
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作者：
Windrem, Martha S.;Schanz, Steven J.;Goldman, Steven A.
新生儿移植的人神经胶质祖细胞（hGPCs）密集地植入低髓鞘的颤颤鼠。我们发现，在hgpc异种移植小鼠中，人类供体细胞继续在整个前脑扩展，系统地取代宿主小鼠胶质细胞。供体细胞的分化受到宿主环境的影响，因此在低髓鞘性颤脑中，更多的供体细胞分化为少突胶质细胞，而在髓鞘野生型中，hGPCs更有可能保持祖细胞的地位。然而，在每个受体中，小鼠GPCs的数量和相对比例都随着时间的推移而下降，伴随着供体hGPCs的有丝分裂扩张和扩散。在新生儿异种移植一年后，移植小鼠的前脑GPC群体大部分，甚至完全是人类起源。因此，新生植入的hGPCs竞争并最终取代小鼠GPCs的宿主群体，最终产生具有人源化胶质祖细胞群体的小鼠。这些人类神经胶质嵌合小鼠应该允许我们在体内使用人类细胞来确定神经胶质对各种神经系统疾病的具体贡献。
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.