Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC
Astrocytes Attenuate Mitochondrial Dysfunctions in Human Dopaminergic Neurons Derived from iPSC
复制标题
DOI：
10.1016/j.stemcr.2017.12.021
复制
发表时间：
2018-02-13
影响因子：
5.9
通讯作者：
Yan, Shirley ShiDu
中科院分区：
文献类型：
--
作者：
Du, Fang;Yu, Qing;Yan, Shirley ShiDu
星形胶质细胞是大脑中数量最多的胶质细胞类型，对于调节大脑微环境至关重要。在各种神经退行性疾病中，星形胶质细胞决定神经病理过程的进展和结果。我们最近揭示了人多能干细胞（hiPSC）衍生的多巴胺能（DA）神经元分化中线粒体功能的直接参与。使用星形胶质细胞-神经元共培养系统，我们在这里表明，星形胶质细胞有效地拯救缺陷的DA神经元的线粒体呼吸链中断的神经发生。星形胶质细胞与缺陷DA神经元的共培养完全恢复了线粒体毒素损伤的线粒体功能和动力学。这些结果表明，星形胶质细胞在维持线粒体发育和生物能量学的hiPSC衍生的DA神经元的分化过程中的意义。我们的研究也提供了一个积极的星形胶质细胞-神经元相互作用的模型，为未来的调查线粒体参与神经发生和神经退行性疾病。
Astrocytes, the most populous glial cell type in the brain, are critical for regulating the brain microenvironment. In various neurodegenerative diseases, astrocytes determine the progression and outcome of the neuropathological process. We have recently revealed the direct involvement of mitochondrial function in human pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neuronal differentiation. Using the astroglial-neuronal co-culture system, we show here that astrocytes effectively rescue defects in neurogenesis of DA neurons with mitochondrial respiratory chain disruption. Co-culture of astrocytes with defective DA neurons completely restored mitochondrial functions and dynamics insulted by mitochondrial toxins. These results suggest the significance of astroglia in maintaining mitochondrial development and bioenergetics during differentiation of hiPSC-derived DA neurons. Our study also provides an active astroglial-neuronal interaction model for future investigation of mitochondrial involvement in neurogenesis and neurodegenerative diseases.