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首页> 外文期刊>The European Journal of Neuroscience >Targeted activation of primitive neural stem cells in the mouse brain
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Targeted activation of primitive neural stem cells in the mouse brain

机译：小鼠脑中原始神经干细胞的靶向激活

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Primitive neural stem cells (pNSCs) are the earliest NSCs to appear in the developing forebrain. They persist into the adult forebrain where they can generate all cells in the neural lineage and therefore hold great potential for brain regeneration. Thus, pNSCs are an ideal population to target to promote endogenous NSC activation. pNSCs can be isolated from the periventricular region as leukaemia inhibitory factor-responsive cells, and comprise a rare population in the adult mouse brain. We hypothesized that the pup periventricular region gives rise to more clonal pNSC-derived neurospheres but that pup-derived pNSCs are otherwise comparable to adult-derived pNSCs, and can be used to identify selective markers and activators of endogenous pNSCs. We tested the self-renewal ability, differentiation capacity and gene expression profile of pup-derived pNSCs and found them each to be comparable to adult-derived pNSCs, including being GFAP(-), nestin(mid), Oct4(+). Next, we used pup pNSCs to test pharmacological compounds to activate pNSCs to promote endogenous brain repair. We hypothesized that pNSCs could be activated by targeting the cell surface proteins C-Kit and ErbB2, which were enriched in pNSCs relative to definitive NSCs (dNSCs) in an invitro screen. C-Kit and ErbB2 signalling inhibition had distinct effects on pNSCs and dNSCs invitro, and when infused directly into the adult brain invivo. Targeted activation of pNSCs with C-Kit and ErbB2 modulation is a valuable strategy to activate the earliest cell in the neural lineage to contribute to endogenous brain regeneration.
机译：原始神经干细胞（pNSC）是最早出现在发育中的前脑的NSC。它们持续进入成年前脑，在那里它们可以产生神经谱系中的所有细胞，因此具有巨大的脑再生潜力。因此，pNSC是靶向促进内源性NSC活化的理想人群。可以从脑室周围区域分离出pNSCs作为白血病抑制因子反应性细胞，并且在成年小鼠脑中包含罕见的种群。我们假设，幼犬的脑室周围区域会产生更多的克隆性pNSC来源的神经球，但是幼犬的pNSCs可以与成人来源的pNSCs相比，并且可以用于鉴定内源性pNSCs的选择性标记和激活剂。我们测试了幼犬衍生的pNSC的自我更新能力，分化能力和基因表达谱，发现它们每个都与成人衍生的pNSC相当，包括GFAP（-），nestin（mid），Oct4（+）。接下来，我们使用幼崽pNSC来测试药理化合物以激活pNSC来促进内源性脑修复。我们假设可以通过靶向细胞表面蛋白C-Kit和ErbB2来激活pNSC，C-Kit和ErbB2在体外筛选中相对于确定的NSC（dNSC）富含pNSC。 C-Kit和ErbB2信号传导抑制对pNSCs和dNSCs体外具有明显的影响，当直接注入成年大脑的体内时也是如此。用C-Kit和ErbB2调节靶向激活pNSCs是激活神经谱系中最早的细胞以促进内源性大脑再生的有价值的策略。

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