Cerebral organoids model human brain development and microcephaly.
Cerebral organoids model human brain development and microcephaly.
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作者：
人类大脑的复杂性使得在模型生物中研究许多大脑疾病变得困难，并突出了对人类大脑发育体外模型的需求。我们已经开发了一种人多能干细胞衍生的3D类器官培养系统，称为脑类器官，其开发了各种离散但相互依赖的脑区域。这些包括含有组织和产生成熟皮质神经元亚型的祖细胞群体的大脑皮质。此外，脑类器官概括了人类皮质发育的特征，即具有丰富的外部放射状胶质干细胞的特征性祖细胞区组织。最后，我们使用RNAi和患者特异性iPS细胞来模拟小头畸形，这是一种难以在小鼠中重现的疾病。我们证明了患者类器官中的过早神经元分化，这是一种可以解释疾病表型的缺陷。我们的数据表明，3D类器官甚至可以重现这种最复杂的人体组织的发育和疾病。
The complexity of the human brain has made it difficult to study many brain disorders in model organisms, and highlights the need for an in vitro model of human brain development. We have developed a human pluripotent stem cell-derived 3D organoid culture system, termed cerebral organoid, which develops various discrete though interdependent brain regions. These include cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNAi and patient-specific iPS cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could explain the disease phenotype. Our data demonstrate that 3D organoids can recapitulate development and disease of even this most complex human tissue.
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影响因子：
21.3
作者：
Gruber, Ralph;Zhou, Zhongwei;Wang, Zhao-Qi
通讯作者：
Wang, Zhao-Qi
DOI：
10.1073/pnas.1002285107
发表时间：
2010-07-20
影响因子：
11.1
作者：
Bedogni, Francesco;Hodge, Rebecca D.;Hevner, Robert F.
通讯作者：
Hevner, Robert F.
影响因子：
16.2
作者：
Hevner, RF;Shi, LM;Rubenstein, JLR
通讯作者：
Rubenstein, JLR
影响因子：
64.5
作者：
CHENN, A;MCCONNELL, SK
通讯作者：
MCCONNELL, SK
影响因子：
64.5
作者：
Lui JH;Hansen DV;Kriegstein AR
通讯作者：
Kriegstein AR