The differentiation of neuronal stem cells into polarized neurons is a well-coordinated process which has mostly been studied in classical non-human model systems, but to what extent these findings are recapitulated in human neurons remains unclear. To study neuronal polarization in human neurons, we cultured hiPSC-derived neurons, characterized early developmental stages, measured electrophysiological responses, and systematically profiled transcriptomic and proteomic dynamics during these steps. The neuron transcriptome and proteome shows extensive remodeling, with differential expression profiles of ~1100 transcripts and ~2200 proteins during neuronal differentiation and polarization. We also identified a distinct axon developmental stage marked by the relocation of axon initial segment proteins and increased microtubule remodeling from the distal (stage 3a) to the proximal (stage 3b) axon. This developmental transition coincides with action potential maturation. Our comprehensive characterization and quantitative map of transcriptome and proteome dynamics provides a solid framework for studying polarization in human neurons.

中文翻译：

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人类 iPSC 衍生神经元极化过程中转录组和蛋白质组动态的定量图谱


神经元干细胞分化为极化神经元是一个协调良好的过程，主要在经典的非人类模型系统中进行研究，但这些发现在人类神经元中的重现程度仍不清楚。为了研究人类神经元的神经元极化，我们培养了 hiPSC 衍生的神经元，表征了早期发育阶段，测量了电生理反应，并系统地分析了这些步骤中的转录组和蛋白质组动力学。神经元转录组和蛋白质组显示出广泛的重塑，在神经元分化和极化过程中具有约 1100 个转录物和约 2200 个蛋白质的差异表达谱。我们还确定了一个独特的轴突发育阶段，其特征是轴突初始片段蛋白的重新定位和从远端（3a 阶段）到近端（3b 阶段）轴突的微管重塑增加。这种发育转变与动作电位的成熟同时发生。我们对转录组和蛋白质组动力学的全面表征和定量图谱为研究人类神经元的极化提供了坚实的框架。