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少突胶质源性和神经源性成年室管膜下区神经干细胞构成不同谱系,并表现出对 Wnt 信号的不同反应性。

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

机构信息

Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, Munich, Germany.

出版信息

Nat Cell Biol. 2013 Jun;15(6):602-13. doi: 10.1038/ncb2736. Epub 2013 May 5.

DOI:10.1038/ncb2736
PMID:23644466
Abstract

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- α positive cells, suggesting that this pathway contributes to the fine tuning of oligodendrogliogenesis in the adult SEZ.

摘要

成年小鼠室管膜下区(SEZ)含有能够产生神经元和少突胶质细胞前体的成体神经干细胞(aNSC)。然而,目前尚不清楚同一个 aNSC 是否能够产生神经元和少突胶质细胞前体,或者这些不同的前体是否构成完全独立的谱系。通过对从小鼠 SEZ 分离出的 aNSC 及其后代进行连续的活体成像和单细胞追踪,研究人员发现 aNSC 仅产生少突胶质细胞或神经元,但在单个谱系中从未同时产生这两种细胞。此外,经典 Wnt 信号通路的激活选择性地刺激了少突胶质细胞谱系中的增殖,导致少突胶质细胞生成大量增加,而不改变神经发生克隆中的谱系选择或增殖。体内激活或抑制经典 Wnt 信号通路分别增加或减少了 Olig2 和 PDGFR-α阳性细胞的数量,这表明该通路有助于调节成年 SEZ 中的少突胶质细胞生成。

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