Wen Li1,2,3, Shanshan Wang1,2,3, Hui He1,2,3, Jianbing Qin1,2,3, Xiang Cheng1,2,3, Heyan Zhao1,2,3, Meiling Tian1,2,3, Xinhua Zhang4,5,6,7, Guohua Jin8,9,10,11. 1. 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. 2. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, No. 19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China. 3. Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, No.19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China. 4. 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. zhangxinhua@ntu.edu.cn. 5. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, No. 19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China. zhangxinhua@ntu.edu.cn. 6. Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, No.19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China. zhangxinhua@ntu.edu.cn. 7. Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong, Jiangsu, China. zhangxinhua@ntu.edu.cn. 8. 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. jguohua@ntu.edu.cn. 9. Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, No. 19 Qixiu Road, No.3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China. jguohua@ntu.edu.cn. 10. Co-Innovation Center of Neuroregeneration, Medical School of Nantong University, No.19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China. jguohua@ntu.edu.cn. 11. Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Medical School of Nantong University, Nantong, Jiangsu, China. jguohua@ntu.edu.cn.
Abstract
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.
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.
Authors: Daniel Saucier; Gabriel Wajnberg; Jeremy Roy; Annie-Pier Beauregard; Simi Chacko; Nicolas Crapoulet; Sébastien Fournier; Anirban Ghosh; Stephen M Lewis; Alier Marrero; Colleen O'Connell; Rodney J Ouellette; Pier Jr Morin Journal: Brain Res Date: 2018-12-12 Impact factor: 3.252
Authors: Yulan Jiang; Cezar Gavrilovici; Mathieu Chansard; Rui Han Liu; Ivana Kiroski; Kari Parsons; Sang Ki Park; G Campbell Teskey; Jong M Rho; Minh Dang Nguyen Journal: J Neurosci Date: 2016-06-15 Impact factor: 6.167