Pyramidal Neurons Derived from Human Pluripotent Stem Cells Integrate Efficiently into Mouse Brain Circuits In Vivo
Pyramidal Neurons Derived from Human Pluripotent Stem Cells Integrate Efficiently into Mouse Brain Circuits In Vivo
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DOI：
10.1016/j.neuron.2012.12.011
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发表时间：
2013-02-06
期刊：
影响因子：
16.2
通讯作者：
Vanderhaeghen, Pierre
中科院分区：
文献类型：
--
作者：
Espuny-Camacho, Ira;Michelsen, Kimmo A.;Vanderhaeghen, Pierre
人类皮质发育的研究对大脑进化和疾病具有重要意义，但由于缺乏实验模型，一直难以捉摸。在这里，我们发现，人胚胎干细胞(ESCs)和诱导多能干细胞(IPSCs)在没有添加形态原的情况下培养，重现皮质生成，导致所有六层身份的功能性锥体神经元的顺序生成。移植到新生小鼠脑内后，人胚胎干细胞来源的皮质神经元融合良好，并建立了与天然皮质神经元相对应的特异性轴突投射和树突模式。在体内，移植的人类皮质神经元的分化和连接在几个月后逐渐复杂化，最终与宿主回路建立功能性突触。我们的数据表明，ESC/IPSC在体外培养的人皮质神经元可以在体内形成具有大脑皮层特征的复杂的生物学特性，从而为人类皮质疾病的建模和脑修复提供了前所未有的机会。
The study of human cortical development has major implications for brain evolution and diseases but has remained elusive due to paucity of experimental models. Here we found that human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. After transplantation into mouse neonatal brain, human ESC-derived cortical neurons integrated robustly and established specific axonal projections and dendritic patterns corresponding to native cortical neurons. The differentiation and connectivity of the transplanted human cortical neurons complexified progressively over several months in vivo, culminating in the establishment of functional synapses with the host circuitry. Our data demonstrate that human cortical neurons generated in vitro from ESC/iPSC can develop complex hodological properties characteristic of the cerebral cortex in vivo, thereby offering unprecedented opportunities for the modeling of human cortex diseases and brain repair.