Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes.
Systematic Three-Dimensional Coculture Rapidly Recapitulates Interactions between Human Neurons and Astrocytes.
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系统的三维共培养迅速概括了人类神经元与星形胶质细胞之间的相互作用。
DOI：
10.1016/j.stemcr.2017.10.026
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发表时间：
2017-12-12
影响因子：
5.9
通讯作者：
Ullian EM
中科院分区：
文献类型：
--
作者：
Krencik R;Seo K;van Asperen JV;Basu N;Cvetkovic C;Barlas S;Chen R;Ludwig C;Wang C;Ward ME;Gan L;Horner PJ;Rowitch DH;Ullian EM
人类星形胶质细胞以动态方式与神经元网络，这种方式仍然很难定义。由于缺乏相关和方便的工具来概括这种复杂的相互作用，我们对这种关系进行建模的能力受到了阻碍。为了解决这一障碍，我们设计了有效的共培养系统，其利用3D类器官样球体（称为小行星），其含有预分化的人多能干细胞（hPSC）衍生的星形胶质细胞（hAstros）与从hPSC衍生的神经干细胞（hNeurons）产生的或通过Neurogenin 2过表达直接诱导的神经元（iNeurons）组合。我们的系统方法快速产生结构复杂的hAstros和突触与iNeurons在高密度共培养精确的数字，允许神经回路功能，疾病建模和药物筛选的改进研究。我们的结论是，这些生物工程神经电路模型系统是可靠的和可扩展的工具，以准确地研究人类星形胶质细胞-神经元功能特性的各个方面，同时易于获得细胞类型特定的操作和观察。描述了一种新的三维“小行星”共培养系统在体外产生了复杂的人类星形胶质细胞特异性形态。该系统产生了星形胶质细胞与突触的快速和紧密的结合。在这篇文章中，Krencik和他的同事们表明，预分化的人类星形胶质细胞与来自多能干细胞的诱导神经元的高密度共培养物在3-5周内诱导成熟特征。这为研究人类神经回路功能的类器官培养提供了一种更快、更明确的替代方法。
Human astrocytes network with neurons in dynamic ways that are still poorly defined. Our ability to model this relationship is hampered by the lack of relevant and convenient tools to recapitulate this complex interaction. To address this barrier, we have devised efficient coculture systems utilizing 3D organoid-like spheres, termed asteroids, containing pre-differentiated human pluripotent stem cell (hPSC)-derived astrocytes (hAstros) combined with neurons generated from hPSC-derived neural stem cells (hNeurons) or directly induced via Neurogenin 2 overexpression (iNeurons). Our systematic methods rapidly produce structurally complex hAstros and synapses in high-density coculture with iNeurons in precise numbers, allowing for improved studies of neural circuit function, disease modeling, and drug screening. We conclude that these bioengineered neural circuit model systems are reliable and scalable tools to accurately study aspects of human astrocyte-neuron functional properties while being easily accessible for cell-type-specific manipulations and observations. Novel three-dimensional “asteroid” coculture system is described Complex human astrocyte-specific morphology is generated in vitro This system produces rapid and tight association of astrocytes with synapses In this article, Krencik and colleagues show that high-density cocultures of pre-differentiated human astrocytes with induced neurons, from pluripotent stem cells, elicit mature characteristics by 3–5 weeks. This provides a faster and more defined alternative method to organoid cultures for investigating human neural circuit function.
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DOI：
10.1523/jneurosci.4707-08.2009
发表时间：
2009-03-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Oberheim NA;Takano T;Han X;He W;Lin JH;Wang F;Xu Q;Wyatt JD;Pilcher W;Ojemann JG;Ransom BR;Goldman SA;Nedergaard M
通讯作者：
Nedergaard M
DOI：
10.1083/jcb.201610056
发表时间：
2017-01-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Simian M;Bissell MJ
通讯作者：
Bissell MJ
影响因子：
56.9
作者：
Bindocci, Erika;Savtchouk, Iaroslav;Volterra, Andrea
通讯作者：
Volterra, Andrea
影响因子：
23.9
作者：
Han, Xiaoning;Chen, Michael;Wang, Fushun;Windrem, Martha;Wang, Su;Shanz, Steven;Xu, Qiwu;Oberheim, Nancy Ann;Bekar, Lane;Betstadt, Sarah;Silva, Alcino J.;Takano, Takahiro;Goldman, Steven A.;Nedergaard, Maiken
通讯作者：
Nedergaard, Maiken
影响因子：
64.8
作者：
Birey F;Andersen J;Makinson CD;Islam S;Wei W;Huber N;Fan HC;Metzler KRC;Panagiotakos G;Thom N;O'Rourke NA;Steinmetz LM;Bernstein JA;Hallmayer J;Huguenard JR;Paşca SP
通讯作者：
Paşca SP