Circumventricular organs: a novel site of neural stem cells in the adult brain.

Circumventricular organs: a novel site of neural stem cells in the adult brain.
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DOI:
10.1016/j.mcn.2009.04.007
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发表时间:
2009-07
影响因子:
3.5
通讯作者:
Lacovitti, Lorraine
Lacovitti, Lorraine
中科院分区:
医学3区
文献类型:
--
作者:
Bennett, Lori;Yang, Ming;Enikolopov, Grigori;Lacovitti, Lorraine

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成年哺乳动物神经系统中的神经发生在前侧脑室的室下区和海马的颗粒下区已得到很好的建立。在这些区域中,神经元被认为起源于神经干细胞,通过其特定中间丝蛋白(巢蛋白、波形蛋白、GFAP)和转录因子(Sox2)的表达来识别。在本研究中,我们发现成年大鼠和小鼠的心室周围器官(CVO)富含表达 Sox2 和细胞周期调节蛋白 Ki67 的巢蛋白 +、GFAP +、波形蛋白 + 细胞。在培养中,这些细胞增殖为神经球并表达神经元(双皮质素+、β-微管蛋白 III+)和神经胶质(S100β+、GFAP+、RIP+)表型特征。此外,我们使用溴脱氧尿苷的体内研究表明,CVO 细胞增殖并经历组成性神经发生和胶质细胞生成。这些发现表明,CVO 可能构成了迄今为止未知的干细胞/祖细胞来源,能够在成人大脑中产生新的神经元和/或神经胶质细胞。
Neurogenesis in the adult mammalian nervous system is now well established in the subventricular zone of the anterolateral ventricle and subgranular zone of the hippocampus. In these regions, neurons are thought to arise from neural stem cells, identified by their expression of specific intermediate filament proteins (nestin, vimentin, GFAP) and transcription factors (Sox2). In the present study, we show that in adult rat and mouse, the circumventricular organs (CVOs) are rich in nestin+, GFAP+, vimentin+ cells which express Sox2 and the cell cycle-regulating protein Ki67. In culture, these cells proliferate as neurospheres and express neuronal (doublecortin+, β-tubulin III+) and glial (S100β+, GFAP+, RIP+) phenotypic traits. Further, our in vivo studies using bromodeoxyuridine show that CVO cells proliferate and undergo constitutive neurogenesis and gliogenesis. These findings suggest that CVOs may constitute a heretofore unknown source of stem/progenitor cells, capable of giving rise to new neurons and/or glia in the adult brain.
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