Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
Neuroscience and Mental Health Research Institute, School of Medicine, Cardiff University, Cardiff CF24 4HQ, UK; School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
Stem Cell Reports. 2019 Feb 12;12(2):191-200. doi: 10.1016/j.stemcr.2018.12.014. Epub 2019 Jan 17.
Striatal interneurons are born in the medial and caudal ganglionic eminences (MGE and CGE) and play an important role in human striatal function and dysfunction in Huntington's disease and dystonia. MGE/CGE-like neural progenitors have been generated from human pluripotent stem cells (hPSCs) for studying cortical interneuron development and cell therapy for epilepsy and other neurodevelopmental disorders. Here, we report the capacity of hPSC-derived MGE/CGE-like progenitors to differentiate into functional striatal interneurons. In vitro, these hPSC neuronal derivatives expressed cortical and striatal interneuron markers at the mRNA and protein level and displayed maturing electrophysiological properties. Following transplantation into neonatal rat striatum, progenitors differentiated into striatal interneuron subtypes and were consistently found in the nearby septum and hippocampus. These findings highlight the potential for hPSC-derived striatal interneurons as an invaluable tool in modeling striatal development and function in vitro or as a source of cells for regenerative medicine.
纹状体中间神经元起源于内侧和尾状神经节隆起（MGE 和 CGE），在亨廷顿病和肌张力障碍中对人类纹状体功能和功能障碍起着重要作用。已经从人多能干细胞（hPSC）中产生了 MGE/CGE 样神经祖细胞，用于研究皮质中间神经元的发育和癫痫及其他神经发育障碍的细胞治疗。在这里，我们报告了 hPSC 衍生的 MGE/CGE 样祖细胞分化为功能性纹状体中间神经元的能力。在体外，这些 hPSC 神经元衍生物在 mRNA 和蛋白质水平上表达皮质和纹状体中间神经元标志物，并表现出成熟的电生理特性。移植到新生大鼠纹状体后，祖细胞分化为纹状体中间神经元亚型，并在附近的隔室和海马中始终存在。这些发现强调了 hPSC 衍生的纹状体中间神经元作为体外模拟纹状体发育和功能的宝贵工具的潜力，或者作为再生医学中细胞来源的潜力。
