Institut Pasteur, Neurobiologie Intégrative des Systèmes Cholinergiques, Département de Neuroscience, CNRS UMR 3571, 25 rue du Dr Roux, 75724, Paris Cedex 15, France.
Institut Pasteur, Neurobiologie Intégrative des Systèmes Cholinergiques, Département de Neuroscience, CNRS UMR 3571, 25 rue du Dr Roux, 75724, Paris Cedex 15, France; Sorbonne Université, Collège Doctoral, 75005, Paris, France.
Dev Biol. 2020 May 1;461(1):86-95. doi: 10.1016/j.ydbio.2020.01.009. Epub 2020 Jan 23.
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".
在体内研究人类神经发育的分子和细胞机制的主要障碍之一是实验模型的稀缺。人类诱导多能干细胞（hiPSC）可以生成神经元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在小鼠大脑皮层中追踪移植的 hiPSC 衍生神经元前体的发育。通过死后免疫组织化学，我们在总共六个月的时间内量化了人类神经元树突模式的分化和成熟。此外，我们还使用颅窗的双光子体内成像技术，在八个月的时间内跟踪整个 hiPSC 衍生的神经元实质。我们发现，移植的 hiPSC 衍生神经元前体在不同的大脑皮层区域表现出“延长”的人类发育程序。这为“实时”进行人类皮质发育及其变化的连续体内研究提供了新的可能性。
