Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences.

Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences.
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DOI:
10.1038/nn.3541
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发表时间:
2013-11
影响因子:
25
通讯作者:
Kriegstein, Arnold R.
Kriegstein, Arnold R.
中科院分区:
医学1区
文献类型:
--
作者:
Hansen, David V.;Lui, Jan H.;Flandin, Pierre;Yoshikawa, Kazuaki;Rubenstein, John L.;Alvarez-Buylla, Arturo;Kriegstein, Arnold R.

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GABA能皮质中间神经元是神经回路复杂性的基础,在人类中数量特别多且多样。在啮齿类动物中,皮质中间神经元起源于苍白球下神经节隆起,但它们在人类中的发育起源是有争议的。我们的特点是发展中的人类神经节隆起,并发现脑室下区(SVZ)在孕中期早期大量扩大,成为密集的神经干细胞和中间祖细胞。与皮质相反,大多数干细胞在神经节隆起SVZ没有保持径向纤维或方向。内侧神经节隆起表现出独特的祖细胞组织和聚类模式,标记物显示,尾神经节隆起产生的皮质中间神经元在人类比在啮齿类动物的比例更大。在切片培养中标记新生神经元和绘制增殖的中间神经元祖细胞的基础上,我们得出结论,绝大多数人皮质中间神经元产生于神经节隆起,包括来自非上皮SVZ干细胞的巨大贡献。
GABAergic cortical interneurons underlie the complexity of neural circuits and are particularly numerous and diverse in humans. In rodents, cortical interneurons originate in the subpallial ganglionic eminences, but their developmental origins in humans are controversial. We characterized the developing human ganglionic eminences and found that the subventricular zone (SVZ) expanded massively during the early second trimester, becoming densely populated with neural stem cells and intermediate progenitor cells. In contrast with the cortex, most stem cells in the ganglionic eminence SVZ did not maintain radial fibers or orientation. The medial ganglionic eminence exhibited unique patterns of progenitor cell organization and clustering, and markers revealed that the caudal ganglionic eminence generated a greater proportion of cortical interneurons in humans than in rodents. On the basis of labeling of newborn neurons in slice culture and mapping of proliferating interneuron progenitors, we conclude that the vast majority of human cortical interneurons are produced in the ganglionic eminences, including an enormous contribution from non-epithelial SVZ stem cells.
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