Pro-maturational Effects of Human iPSC-Derived Cortical Astrocytes upon iPSC-Derived Cortical Neurons
Pro-maturational Effects of Human iPSC-Derived Cortical Astrocytes upon iPSC-Derived Cortical Neurons
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DOI：
10.1016/j.stemcr.2020.05.003
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发表时间：
2020-07-14
影响因子：
5.9
通讯作者：
Akerman, Colin J.
中科院分区：
文献类型：
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作者：
Hedegaard, Anne;Monzon-Sandoval, Jimena;Akerman, Colin J.
星形胶质细胞通过提供营养支持、调节细胞外环境和调节突触信号传导来影响神经元的成熟和功能。诱导多能干细胞（iPSC）技术的出现为验证和重新评估动物研究的见解提供了一个人类系统。在这里，我们着手研究人类星形胶质细胞和神经元之间的相互作用，来自一个共同的皮质祖细胞池，从而概括在体内皮质发育方面。我们发现，皮质iPSC衍生的星形胶质细胞表现出许多星形胶质细胞的分子和功能特征。此外，光遗传学和电生理学共培养实验表明，iPSC-星形胶质细胞可以主动调节正在进行的突触传递，并对iPSC衍生的皮层神经元的发育网络发挥促成熟作用。最后，转录组学分析暗示了星形胶质细胞对iPSC衍生的神经元的促成熟作用中的突触相关细胞外信号传导。这项工作有助于为未来研究人类健康和疾病中星形胶质细胞与神经元的相互作用奠定基础。
Astrocytes influence neuronal maturation and function by providing trophic support, regulating the extracellular environment, and modulating signaling at synapses. The emergence of induced pluripotent stem cell (iPSC) technology offers a human system with which to validate and re-evaluate insights from animal studies. Here, we set out to examine interactions between human astrocytes and neurons derived from a common cortical progenitor pool, thereby recapitulating aspects of in vivo cortical development. We show that the cortical iPSC-derived astrocytes exhibit many of the molecular and functional hallmarks of astrocytes. Furthermore, optogenetic and electrophys-iological co-culture experiments reveal that the iPSC-astrocytes can actively modulate ongoing synaptic transmission and exert pro-maturational effects upon developing networks of iPSC-derived cortical neurons. Finally, transcriptomic analyses implicate syn-apse-associated extracellular signaling in the astrocytes' pro-maturational effects upon the iPSC-derived neurons. This work helps lay the foundation for future investigations into astrocyte-to-neuron interactions in human health and disease.