Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to Wnt signalling

Oligodendrogliogenic and neurogenic adult subependymal zone neural stem cells constitute distinct lineages and exhibit differential responsiveness to Wnt signalling
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DOI:
10.1038/ncb2736
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发表时间:
2013-06-01
影响因子:
21.3
通讯作者:
Berninger, Benedikt
Berninger, Benedikt
中科院分区:
生物学1区
文献类型:
--
作者:
Ortega, Felipe;Gascon, Sergio;Berninger, Benedikt

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成年小鼠室管膜下区(SEZ)拥有成体神经干细胞(aNSCs),这些干细胞可以产生神经元和少突胶质后代。然而,尚不清楚相同的aNSC是否可以产生神经元和少突胶质后代,或者这些不同的后代是否构成完全独立的谱系。从小鼠SEZ中分离的aNSCs及其后代的连续实时成像和单细胞跟踪显示,aNSCs只产生少突胶质细胞或神经元,但从未在单一谱系中同时产生。此外,典型Wnt信号的激活选择性地刺激了少突胶质细胞谱系内的增殖,导致少突胶质细胞发生的大量增加,而不改变谱系选择或神经原性克隆内的增殖。体内激活或抑制典型Wnt信号分别增加或减少Olig2和pdgfr - α阳性细胞的数量,表明该途径有助于成人经济特区少突胶质细胞形成的微调。
The adult mouse subependymal zone (SEZ) harbours adult neural stem cells (aNSCs) that give rise to neuronal and oligodendroglial progeny. However it is not known whether the same aNSC can give rise to neuronal and oligodendroglial progeny or whether these distinct progenies constitute entirely separate lineages. Continuous live imaging and single-cell tracking of aNSCs and their progeny isolated from the mouse SEZ revealed that aNSCs exclusively generate oligodendroglia or neurons, but never both within a single lineage. Moreover, activation of canonical Wnt signalling selectively stimulated proliferation within the oligodendrogliogenic lineage, resulting in a massive increase in oligodendrogliogenesis without changing lineage choice or proliferation within neurogenic clones. In vivo activation or inhibition of canonical Wnt signalling respectively increased or decreased the number of Olig2 and PDGFR-alpha positive cells, suggesting that this pathway contributes to the fine tuning of oligodendrogliogenesis in the adult SEZ.