Antonov S A, Novosadova E V, Kobylyansky A G, Illarioshkin S N, Tarantul V Z, Grivennikov I A
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
Research Center of Neurology, Moscow, 125367, Russia.
Biochemistry (Mosc). 2019 Mar;84(3):310-320. doi: 10.1134/S0006297919030131.
Ionotropic glutamate and GABA receptors regulate the differentiation and determine the functional properties of mature neurons. Both insufficient and excessive activity of these neurotransmission systems are associated with various nervous system diseases. Our knowledge regarding the expression profiles of these receptors and the mechanisms of their regulation during the differentiation of specialized human neuron subtypes is limited. Here the expression profiles of the NMDA and GABA receptor subunits were explored during in vitro differentiation of human induced pluripotent stem cells (iPSCs) into ventral mesencephalic neurons. The correlation between the neuronal maturation and the expression dynamics of these genes was investigated, and the functional activity of these receptors was assessed by calcium imaging. The role of NMDA and GABA receptors in neurite outgrowth and the development of spontaneous activity was analyzed using the viral transduction of neural progenitors with the reporter genes TagGFP and TagRFP. The data indicate that agonists of the investigated receptors can be employed for optimization of existing protocols for neural differentiation of iPSCs, in particular for acceleration of neuronal maturation.
离子型谷氨酸和GABA受体调节成熟神经元的分化并决定其功能特性。这些神经传递系统的活性不足和过度都与各种神经系统疾病有关。我们对于这些受体在特定人类神经元亚型分化过程中的表达谱及其调控机制的了解有限。在此，我们探索了人类诱导多能干细胞（iPSC）在体外分化为腹侧中脑神经元过程中NMDA和GABA受体亚基的表达谱。研究了神经元成熟与这些基因表达动态之间的相关性，并通过钙成像评估了这些受体的功能活性。使用带有报告基因TagGFP和TagRFP的病毒转导神经祖细胞，分析了NMDA和GABA受体在神经突生长和自发活动发展中的作用。数据表明，所研究受体的激动剂可用于优化现有的iPSC神经分化方案，特别是用于加速神经元成熟。
