海马体外泌体诱导神经干细胞分化过程中Ndel1的表达及功能
Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomesticle.
作者信息
Li Wen, Wang Shanshan, He Hui, Qin Jianbing, Cheng Xiang, Zhao Heyan, Tian Meiling, Zhang Xinhua, Jin Guohua
机构信息
Department of Human Anatomy, Institute of Neurobiology, Medical School of Nantong University, No. 19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, No. 19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China.
出版信息
Stem Cell Res Ther. 2021 Jan 9;12(1):51. doi: 10.1186/s13287-020-02119-2.
BACKGROUND
In the brain of adult mammals, neural stem cells persist in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus, which are specialized niches with proliferative capacity. Most neural stem cells are in a quiescent state, but in response to extrinsic stimuli, they can exit from quiescence and become reactivated to produce new neurons, so neural stem cells are considered to be a potential source for cell replacement therapy of many nervous system diseases. We characterized the expression of Ndel1 during the differentiation of neural stem cells induced by hippocampus exosomes, and assessed the effect of Ndel1 on neural stem cells differentiation.
METHODS
Hippocampal exosomes were isolated and extracted, and co-cultured exosomes with neural stem cells. Western blot, flow cytometry, and immunofluorescence analyses were used to analyze expression of neuronal markers. Further, utilizing high-throughput RNA sequencing technology, we found that nudE neurodevelopment protein 1-like 1 was significantly upregulated in exosomes derived from denervated hippocampus, and then characterized its mechanism and function during neural stem cells differentiation by qRT-PCR, western blot, flow cytometry, and immunofluorescence analyses.
RESULTS
Our results revealed that exosomes of denervated hippocampus promoted the differentiation of neural stem cells into neuron. Hence, we identified that nudE neurodevelopment protein 1-like 1 was significantly upregulated and highly expressed in the nervous system. In addition, we found that miR-107-3p may regulate neural stem cell differentiation by targeting Ndel1.
CONCLUSIONS
Our results revealed that deafferentation of the hippocampal exosomes co-cultured with neural stem cells could promote them to differentiate into neurons. Hence, we found that miR-107-3p may regulate neural stem cells differentiation by targeting Ndel1. Importantly, Ndel1 enhanced spatial learning and hippocampal neurogenesis in rats after fimbria fornix transection in vivo. These findings set the stage for a better understanding of neurogenesis, a process that 1 day may inspire new treatments for central nervous system diseases.
背景
在成年哺乳动物大脑中，神经干细胞存在于侧脑室的室下区和齿状回的颗粒下区，这些是具有增殖能力的特殊微环境。大多数神经干细胞处于静止状态，但在外部刺激下，它们可以从静止状态退出并重新激活以产生新的神经元，因此神经干细胞被认为是许多神经系统疾病细胞替代治疗的潜在来源。我们对海马体外泌体诱导神经干细胞分化过程中Ndel1的表达进行了表征，并评估了Ndel1对神经干细胞分化的影响。
方法
分离并提取海马体外泌体，并将其与神经干细胞共培养。采用蛋白质免疫印迹法、流式细胞术和免疫荧光分析来分析神经元标志物的表达。此外，利用高通量RNA测序技术，我们发现神经发育蛋白nudE样蛋白1在去神经支配海马体来源的外泌体中显著上调，然后通过实时定量聚合酶链反应、蛋白质免疫印迹法、流式细胞术和免疫荧光分析来表征其在神经干细胞分化过程中的机制和功能。
结果
我们的结果表明，去神经支配海马体的外泌体促进神经干细胞向神经元分化。因此，我们确定神经发育蛋白nudE样蛋白1在神经系统中显著上调并高表达。此外，我们发现miR-107-3p可能通过靶向Ndel1来调节神经干细胞分化。
结论
我们的结果表明，与神经干细胞共培养的去传入海马体的外泌体可促进它们分化为神经元。因此，我们发现miR-107-3p可能通过靶向Ndel1来调节神经干细胞分化。重要的是，在体内穹窿海马伞横断后，Ndel1增强了大鼠的空间学习能力和海马神经发生。这些发现为更好地理解神经发生奠定了基础，这一过程有朝一日可能会激发中枢神经系统疾病的新治疗方法。
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