Microglial colonisation of the developing brain is facilitated by clonal expansion of highly proliferative progenitors and follows an allometric scaling

Microglial colonisation of the developing brain is facilitated by clonal expansion of highly proliferative progenitors and follows an allometric scaling
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高度增殖的祖细胞的克隆扩张促进了发育中大脑的小胶质细胞定植,并遵循异速生长缩放

DOI:
10.1101/2022.09.15.507569
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发表时间:
2022
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通讯作者:
Barry-Carroll L
Barry-Carroll L
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作者:
Barry-Carroll L

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小胶质细胞在胚胎发育早期从卵黄囊产生并进入大脑。进入后,小胶质细胞进行原位增殖,并最终在小鼠出生后第三周定植在整个大脑中。然而,其发展扩张的复杂性仍不清楚。在这里,我们的特点在胚胎和出生后的发展过程中,使用互补的命运映射技术的小胶质细胞的增殖动力学。我们证明,大脑的发育殖民化是由高度增殖的小胶质祖细胞占据整个大脑的空间龛克隆扩张促进的。此外,小胶质细胞的空间分布开关从一个集群的随机模式之间的胚胎和后期出生后的发展。有趣的是,小胶质细胞数量的发育增加遵循大脑以异速生长的方式成比例增长,直到建立马赛克分布。总的来说,我们的研究结果提供了深入了解空间竞争如何通过发育过程中的克隆扩张来驱动小胶质细胞定植。
Microglia arise from the yolk sac and enter the brain during early embryogenesis. Upon entry, microglia undergoin situproliferation and eventually colonize the entire brain by the third postnatal week in mice. However, the intricacies of their developmental expansion remain unclear. Here, we characterize the proliferative dynamics of microglia during embryonic and postnatal development using complementary fate-mapping techniques. We demonstrate that the developmental colonization of the brain is facilitated by clonal expansion of highly proliferative microglial progenitors that occupy spatial niches throughout the brain. Moreover, the spatial distribution of microglia switches from a clustered to a random pattern between embryonic and late postnatal development. Interestingly, the developmental increase in microglial numbers follows the proportional growth of the brain in an allometric manner until a mosaic distribution has been established. Overall, our findings offer insight into how the competition for space may drive microglial colonization by clonal expansion during development.
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