Neural stem cells in the adult olfactory bulb core generate mature neurons in vivo,STEM CELLS

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Neural stem cells in the adult olfactory bulb core generate mature neurons in vivo
STEM CELLS ( IF 4.0 ) Pub Date : 2021-05-08 , DOI: 10.1002/stem.3393
Çağla Defteralı _{1,

2} , Mireia Moreno-Estellés _{3,

4} , Carlos Crespo ₅ , Eva Díaz-Guerra _{1,

2} , María Díaz-Moreno ₃ , Eva Vergaño-Vera _{1,

2} , Vanesa Nieto-Estévez _{1,

2} , Anahí Hurtado-Chong _{1,

2} , Antonella Consiglio _{6,

7} , Helena Mira _{3,

4} , Carlos Vicario _{1,

2}

Affiliation

Although previous studies suggest that neural stem cells (NSCs) exist in the adult olfactory bulb (OB), their location, identity, and capacity to generate mature neurons in vivo has been little explored. Here, we injected enhanced green fluorescent protein (EGFP)-expressing retroviral particles into the OB core of adult mice to label dividing cells and to track the differentiation/maturation of any neurons they might generate. EGFP-labeled cells initially expressed adult NSC markers on days 1 to 3 postinjection (dpi), including Nestin, GLAST, Sox2, Prominin-1, and GFAP. EGFP⁺-doublecortin (DCX) cells with a migratory morphology were also detected and their abundance increased over a 7-day period. Furthermore, EGFP-labeled cells progressively became NeuN⁺ neurons, they acquired neuronal morphologies, and they became immunoreactive for OB neuron subtype markers, the most abundant representing calretinin expressing interneurons. OB-NSCs also generated glial cells, suggesting they could be multipotent in vivo. Significantly, the newly generated neurons established and received synaptic contacts, and they expressed presynaptic proteins and the transcription factor pCREB. By contrast, when the retroviral particles were injected into the subventricular zone (SVZ), nearly all (98%) EGFP⁺-cells were postmitotic when they reached the OB core, implying that the vast majority of proliferating cells present in the OB are not derived from the SVZ. Furthermore, we detected slowly dividing label-retaining cells in this region that could correspond to the population of resident NSCs. This is the first time NSCs located in the adult OB core have been shown to generate neurons that incorporate into OB circuits in vivo.

中文翻译：

成人嗅球核心中的神经干细胞在体内产生成熟的神经元

尽管以前的研究表明神经干细胞 (NSC) 存在于成人嗅球 (OB) 中，但它们的位置、身份和在体内产生成熟神经元的能力几乎没有被探索过。在这里，我们将表达增强型绿色荧光蛋白 (EGFP) 的逆转录病毒颗粒注入成年小鼠的 OB 核心，以标记分裂细胞并跟踪它们可能产生的任何神经元的分化/成熟。EGFP 标记的细胞最初在注射后第 1 至 3 天 (dpi) 表达成人 NSC 标记，包括 Nestin、GLAST、Sox2、Prominin-1 和 GFAP。还检测到具有迁移形态的EGFP ⁺ -doublecortin (DCX) 细胞，并且它们的丰度在 7 天内增加。此外，EGFP 标记的细胞逐渐变成 NeuN ⁺神经元，它们获得了神经元形态，并且它们对 OB 神经元亚型标记物具有免疫反应性，最丰富的代表表达钙调蛋白的中间神经元。OB-NSCs 还产生神经胶质细胞，表明它们在体内可能是多能的。重要的是，新生成的神经元建立并接受了突触接触，它们表达突触前蛋白和转录因子 pCREB。相比之下，当逆转录病毒颗粒被注入脑室下区 (SVZ) 时，几乎所有 (98%) EGFP ⁺-细胞在到达 OB 核心时是有丝分裂后的，这意味着 OB 中存在的绝大多数增殖细胞不是来自 SVZ。此外，我们在该区域检测到缓慢分裂的标记保留细胞，这些细胞可能对应于常驻 NSC 的数量。这是第一次显示位于成人 OB 核心中的 NSCs 可以在体内产生并入 OB 回路的神经元。

更新日期：2021-05-08

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