Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke
Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke
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DOI：
10.1038/nn.2268
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发表时间：
2009-03-01
影响因子：
25
通讯作者：
Frisen, Jonas
中科院分区：
文献类型：
--
作者：
Carlen, Marie;Meletis, Konstantinos;Frisen, Jonas
在成年哺乳动物脑中的离散区域中，神经元由干细胞连续产生。我们发现侧脑室的室管膜细胞是静止的，在正常条件下对小鼠的成年神经发生没有贡献，而是在中风时产生成神经细胞和星形胶质细胞。室管膜细胞的静止是由典型的Notch信号转导积极维持的。在未受伤的动物中抑制这一通路允许室管膜细胞进入细胞周期并产生嗅球神经元，而强迫Notch信号传导足以阻断室管膜细胞对中风的反应。室管膜细胞因中风而耗尽，无法充分自我更新以维持其自身数量。因此，尽管室管膜细胞在中风后作为神经谱系中的原代细胞产生神经元和神经胶质细胞，但它们在这些条件下不满足干细胞的定义标准，而是作为损伤招募的储库。
Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.