Paavilainen Tanja, Pelkonen Anssi, Mäkinen Meeri E-L, Peltola Marja, Huhtala Heini, Fayuk Dmitriy, Narkilahti Susanna
NeuroGroup, BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland.
Faculty of Social Sciences, University of Tampere, Arvo Ylpön katu 34, 33520 Tampere, Finland.
Stem Cell Res. 2018 Mar;27:151-161. doi: 10.1016/j.scr.2018.01.018. Epub 2018 Jan 31.
Long-term neural differentiation of human pluripotent stem cells (hPSCs) is associated with enhanced neuronal maturation, which is a necessity for creation of representative in vitro models. It also induces neurogenic-to-gliogenic fate switch, increasing proportion of endogenous astrocytes formed from the common neural progenitors. However, the significance of prolonged differentiation on the neural cell type composition and functional development of hPSC-derived neuronal cells has not been well characterized. Here, we studied two hPSC lines, both of which initially showed good neuronal differentiation capacity. However, the propensity for endogenous astrogenesis and maturation state after extended differentiation varied. Live cell calcium imaging revealed that prolonged differentiation facilitated maturation of GABAergic signaling. According to extracellular recordings with microelectrode array (MEA), neuronal activity was limited to fewer areas of the culture, which expressed more frequent burst activity. Efficient maturation after prolonged differentiation also promoted organization of spontaneous activity by burst compaction. These results suggest that although prolonged neural differentiation can be challenging, it has beneficial effect on functional maturation, which can also improve transition to different neural in vitro models and applications.
人类多能干细胞（hPSC）的长期神经分化与神经元成熟的增强相关，这是创建具有代表性的体外模型所必需的。它还会诱导神经源性向胶质源性命运转换，增加由共同神经祖细胞形成的内源性星形胶质细胞的比例。然而，延长分化对hPSC衍生神经元细胞的神经细胞类型组成和功能发育的意义尚未得到充分表征。在这里，我们研究了两条hPSC系，它们最初都表现出良好的神经元分化能力。然而，延长分化后的内源性星形胶质细胞生成倾向和成熟状态各不相同。活细胞钙成像显示，延长分化促进了GABA能信号的成熟。根据微电极阵列（MEA）的细胞外记录，神经元活动局限于培养物中较少的区域，这些区域表现出更频繁的爆发活动。延长分化后的有效成熟还通过爆发压缩促进了自发活动的组织。这些结果表明，尽管延长神经分化可能具有挑战性，但它对功能成熟具有有益影响，这也可以改善向不同神经体外模型和应用的转换。
