Hosseini Kimia, Philippot Gaëtan, Salomonsson Sara B, Cediel-Ulloa Andrea, Gholizadeh Elnaz, Fredriksson Robert
Department of Pharmaceutical Bioscience, Uppsala University, Sweden.
Department of Organismal Biology, Uppsala University, Sweden.
IBRO Neurosci Rep. 2025 Apr 17;18:679-689. doi: 10.1016/j.ibneur.2025.04.013. eCollection 2025 Jun.
Neurodevelopmental studies employing animal models encounter challenges due to interspecies differences and ethical concerns. Maturing neurons of human origin, undergoing several developmental stages, present a powerful alternative. In this study, human embryonic stem cell (H9 cell line) was differentiated into neural stem cells and subsequently matured into neurons over 30 days. Ion AmpliSeq™ was used for transcriptomic characterization of human stem cell-derived neurons at multiple time points. Data analysis revealed a progressive increase of markers associated with neuronal development and astrocyte markers, indicating the establishment of a co-culture accommodating both glial and neurons. Transcriptomic and pathway enrichment analysis also revealed a more pronounced GABAergic phenotype in the neurons, signifying their specialization toward this cell type. The findings confirm the robustness of these cells across different passages and demonstrate detailed progression through stages of development. The model is intended for neurodevelopmental applications and can be adapted to investigate how genetic modifications or exposure to chemicals, pharmaceuticals, and other environmental factors influence neurons and glial maturation.
由于种间差异和伦理问题，利用动物模型进行神经发育研究面临挑战。源自人类的成熟神经元要经历几个发育阶段，是一种强大的替代方案。在本研究中，人类胚胎干细胞（H9细胞系）被分化为神经干细胞，随后在30天内成熟为神经元。Ion AmpliSeq™用于在多个时间点对人类干细胞衍生神经元进行转录组学表征。数据分析显示，与神经元发育相关的标志物和星形胶质细胞标志物逐渐增加，表明建立了一种同时容纳神经胶质细胞和神经元的共培养体系。转录组学和通路富集分析还显示，神经元中GABA能表型更为明显，表明它们向这种细胞类型特化。这些发现证实了这些细胞在不同传代中的稳健性，并展示了其在发育阶段的详细进展。该模型旨在用于神经发育应用，可用于研究基因修饰或接触化学物质、药物和其他环境因素如何影响神经元和神经胶质细胞的成熟。
