Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA.
Department of Pharmacology and Toxicology, and Higuchi Bioscience Center, School of Pharmacy, University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA.
Stem Cell Reports. 2018 Feb 13;10(2):366-374. doi: 10.1016/j.stemcr.2017.12.021. Epub 2018 Jan 27.
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.
星形胶质细胞是大脑中最丰富的神经胶质细胞类型，对调节大脑微环境至关重要。在各种神经退行性疾病中，星形胶质细胞决定了神经病理过程的进展和结果。我们最近揭示了线粒体功能在人多能干细胞（hiPSC）衍生的多巴胺能（DA）神经元分化中的直接参与。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可以有效地挽救线粒体呼吸链中断导致的 DA 神经元神经发生缺陷。与有缺陷的 DA 神经元共培养完全恢复了由线粒体毒素引起的线粒体功能和动力学损伤。这些结果表明星形胶质细胞在维持 hiPSC 衍生的 DA 神经元分化过程中线粒体发育和生物能量的重要性。我们的研究还为未来研究线粒体在神经发生和神经退行性疾病中的作用提供了一个活跃的星形胶质细胞-神经元相互作用模型。
