One of the main obstacles for studying the molecular and cellular mechanisms underlying human neurodevelopment in vivo is the scarcity of experimental models. The discovery that neurons can be generated from human induced pluripotent stem cells (hiPSCs) paves the way for novel approaches that are stem cell-based. Here, we developed a technique to follow the development of transplanted hiPSC-derived neuronal precursors in the cortex of mice over time. Using post-mortem immunohistochemistry we quantified the differentiation and maturation of dendritic patterns of the human neurons over a total of six months. In addition, entirely hiPSC-derived neuronal parenchyma was followed over eight months using two-photon in vivo imaging through a cranial window. We found that transplanted hiPSC-derived neuronal precursors exhibit a "protracted" human developmental programme in different cortical areas. This offers novel possibilities for the sequential in vivo study of human cortical development and its alteration, followed in "real time".

中文翻译：

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人iPSC衍生的锥体神经元的长期发育在移植到新生小鼠皮层后进行了量化。

研究体内人类神经发育基础的分子和细胞机制的主要障碍之一是缺乏实验模型。神经元可以从人诱导的多能干细胞（hiPSC）生成的发现为基于干细胞的新方法铺平了道路。在这里，我们开发了一种技术，可以随着时间的推移跟踪在小鼠皮层中移植的hiPSC衍生的神经元前体的发育。使用死后免疫组织化学，我们量化了总共六个月中人类神经元树突模式的分化和成熟。另外，在整个八个月中，通过颅窗使用两光子体内成像对完全源自hiPSC的神经实质进行了追踪。我们发现，移植的hiPSC衍生的神经元前体表现出“持久” 不同皮质区域的人类发展计划。这为随后的“实时”体内人类皮层发育及其改变的顺序体内研究提供了新颖的可能性。