Abstract：
Germinal activity persists throughout life within the ventricular-subventricular zone (V-SVZ) of the postnatal forebrain due to the presence of neural stem cells (NSCs). Accumulating evidence points to a recruitment for these cells following early brain injuries and suggests their amenability to manipulations. We used chronic hypoxia as a rodent model of early brain injury to investigate the reactivation of cortical progenitors at postnatal times. Our results reveal an increased proliferation and production of glutamatergic progenitors within the dorsal V-SVZ. Fate mapping of V-SVZ NSCs demonstrates their contribution to de novo cortical neurogenesis. Transcriptional analysis of glutamatergic progenitors shows parallel changes in methyltransferase 14 (Mettl14) and Wnt/β-catenin signaling. In agreement, manipulations through genetic and pharmacological activation of Mettl14 and the Wnt/β-catenin pathway, respectively, induce neurogenesis and promote newly-formed cell maturation. Finally, labeling of young adult NSCs demonstrates that pharmacological NSC activation has no adverse effects on the reservoir of V-SVZ NSCs and on their germinal activity.
摘要：
由于神经干细胞（NSC）的存在，生发活动在出生后前脑的心室-心室下区（V-SVZ）中持续存在。越来越多的证据表明，早期脑损伤后这些细胞被募集，并表明它们对操纵的适应性。我们使用慢性缺氧作为早期脑损伤的啮齿动物模型，以研究出生后皮质祖细胞的再激活。我们的结果表明，背侧V-SVZ中谷氨酸能祖细胞的增殖和产生增加。V-SVZNSC的命运作图证明了它们对从头皮质神经发生的贡献。谷氨酸能祖细胞的转录分析显示甲基转移酶14（Mettl14）和Wnt/β-catenin信号传导的平行变化。在协议中,通过Mettl14和Wnt/β-catenin途径的遗传和药理激活进行操作，分别,诱导神经发生并促进新形成的细胞成熟。最后,年轻成年NSC的标记表明，药理NSC激活对V-SVZNSC的储库及其生发活性没有不利影响。
