Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis.
Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis.
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DOI：
10.1523/jneurosci.3095-08.2009
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发表时间：
2009-02-11
期刊：
影响因子：
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通讯作者：
Wu H
中科院分区：
文献类型：
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作者：
Gregorian C;Nakashima J;Le Belle J;Ohab J;Kim R;Liu A;Smith KB;Groszer M;Garcia AD;Sofroniew MV;Carmichael ST;Kornblum HI;Liu X;Wu H
在这里，我们表明，在室管膜下区（SEZ）的成体神经干细胞亚群中的PTEN的条件性缺失导致持续增强的神经干细胞自我更新，而没有疲惫的迹象。这些Pten无效的SEZ出生的神经干细胞和后代可以遵循内源性迁移，分化和整合途径，并有助于嗅球中的组成性神经发生。因此，Pten缺失的动物具有增加的嗅球质量和增强的嗅觉功能。嗅球内pten缺失细胞可与周围嗅上皮建立正常联系，帮助嗅球从急性损伤中恢复。在局灶性中风后，Pten无效祖细胞引起更多数量的神经母细胞迁移到梗死周围皮质。然而，与嗅球相反，没有观察到显著的长期存活和整合，表明中风后新生神经元的长期存活需要额外的因素。这些数据表明，操纵PTEN控制的信号传导途径可能是一个有用的步骤，在促进内源性神经干/祖细胞的扩增，用于治疗疾病或病变的区域与组成性神经发生。
Here we show that conditional deletion of PTEN in a subpopulation of adult neural stem cells in the subependymal zone (SEZ) leads to persistently enhanced neural stem cell self-renewal without sign of exhaustion. These Pten null SEZ-born neural stem cells and progenies can follow the endogenous migration, differentiation, and integration pathways and contribute to the constitutive neurogenesis in the olfactory bulb. As a result, the Pten deleted animals have increased olfactory bulb mass and enhanced olfactory function. Pten null cells in the olfactory bulb can establish normal connections with peripheral olfactory epithelium and help olfactory bulb recovery from acute damage. Following a focal stroke, Pten null progenitors give rise to greater numbers of neuroblasts that migrate to peri-infarct cortex. However, contrary to olfactory bulb, no significant long-term survival and integration can be observed, indicating that additional factors are necessary for long-term survival of newly born neurons after stroke. These data suggest that manipulating PTEN-controlled signaling pathways may be a useful step in facilitating endogenous neural stem/progenitor expansion for the treatment of disorders or lesions in regions associated with constitutive neurogenesis.