Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions.
Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions.
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从多能干细胞生成人类神经元和少突胶质细胞，用于模拟神经元-少突胶质细胞相互作用。
DOI：
10.3791/61778
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发表时间：
2020-11-09
期刊：
影响因子：
--
通讯作者：
Huang YA
中科院分区：
文献类型：
--
作者：
Assetta B;Tang C;Bian J;O'Rourke R;Connolly K;Brickler T;Chetty S;Huang YA
在阿尔茨海默病(AD)和其他神经退行性疾病中，少突胶质细胞衰竭是常见的早期病理特征，但它如何促进疾病的发展和进展，特别是大脑灰质，在很大程度上仍不清楚。少突胶质细胞系细胞的功能障碍以髓鞘形成不足和少突胶质前体细胞(OPC)自我更新受损为特征。这两个缺陷至少部分是由神经元和少突胶质细胞之间的相互作用沿病理的建立中断引起的。OPC在中枢神经系统发育过程中形成髓鞘少突胶质细胞。在成熟的大脑皮层中，OPC是主要的增殖细胞(约占脑细胞总数的5%)，并以神经活动依赖的方式控制新髓鞘的形成。由于缺乏适当的工具，这种神经元到少突胶质细胞的通讯方式的研究严重不足，特别是在神经退行性疾病如阿尔茨海默病的背景下。近年来，我们的团队和其他人在改进目前可用的方案方面取得了重大进展，这些方案可以从人类多能干细胞单独生成功能神经元和少突胶质细胞。在这篇手稿中，我们描述了我们的优化程序，包括建立一个共培养系统来模拟神经元-少突胶质细胞连接。我们的说明性结果表明，OPC/少突胶质细胞对脑淀粉样变性和突触完整性有意想不到的贡献，并强调了这种方法在AD研究中的实用性。这种简化论的方法是一个强大的工具，可以从大脑内部固有的复杂性中剖析特定的异细胞相互作用。我们在这里描述的方案有望促进未来对神经变性发病机制中的少突胶质细胞缺陷的研究。由于工具和方法的不足，人们对神经退行性变中神经元-神经胶质细胞的相互作用还没有很好的了解。在这里，我们描述了从人类多能干细胞中获得诱导神经元、少突胶质前体细胞和少突胶质细胞的优化方案，并提供了这些方法在了解阿尔茨海默病细胞类型特异性贡献方面的价值的例子。
In Alzheimer’s disease (AD) and other neurodegenerative disorders, oligodendroglial failure is a common early pathological feature, but how it contributes to disease development and progression, particularly in the gray matter of the brain, remains largely unknown. The dysfunction of oligodendrocyte lineage cells is hallmarked by deficiencies in myelination and impaired self-renewal of oligodendrocyte precursor cells (OPCs). These two defects are caused at least in part by disruption of interactions between neuron and oligodendrocytes along the buildup of pathology. OPCs give rise to myelinating oligodendrocytes during CNS development. In the mature brain cortex, OPCs are the major proliferative cells (comprising ~5% of total brain cells) and control new myelin formation in a neural activity-dependent manner. Such neuron-to-oligodendrocyte communications are significantly understudied, especially in the context of neurodegenerative conditions such as AD, due to the lack of appropriate tools. In recent years, our group and others have made significant progress to improve currently available protocols to generate functional neurons and oligodendrocytes individually from human pluripotent stem cells. In this manuscript, we describe our optimized procedures, including the establishment of a co-culture system to model the neuron-oligodendrocyte connections. Our illustrative results suggest an unexpected contribution from OPCs/oligodendrocytes to the brain amyloidosis and synapse integrity, and highlight the utility of this methodology for AD research. This reductionist approach is a powerful tool to dissect the specific hetero-cellular interactions out of the inherent complexity inside the brain. The protocols we describe here are expected to facilitate future studies on oligodendroglial defects in the pathogenesis of neurodegeneration. The neuron-glial interactions in neurodegeneration are not well understood due to inadequate tools and methods. Here we describe optimized protocols to obtain induced neurons, oligodendrocyte precursor cells, and oligodendrocytes from human pluripotent stem cells and provide examples of the values of these methods in understanding cell-type-specific contributions in Alzheimer’s disease.
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影响因子：
23.9
作者：
Li L;Tian E;Chen X;Chao J;Klein J;Qu Q;Sun G;Sun G;Huang Y;Warden CD;Ye P;Feng L;Li X;Cui Q;Sultan A;Douvaras P;Fossati V;Sanjana NE;Riggs AD;Shi Y
通讯作者：
Shi Y
影响因子：
25
作者：
Hughes EG;Orthmann-Murphy JL;Langseth AJ;Bergles DE
通讯作者：
Bergles DE
影响因子：
5.9
作者：
Douvaras, Panagiotis;Wang, Jing;Zimmer, Matthew;Hanchuk, Stephanie;O'Bara, Melanie A.;Sadiq, Saud;Sim, Fraser J.;Goldman, James;Fossati, Valentina
通讯作者：
Fossati, Valentina
在人皮质球体中诱导髓鞘的少突胶质细胞。
影响因子：
48
作者：
Madhavan M;Nevin ZS;Shick HE;Garrison E;Clarkson-Paredes C;Karl M;Clayton BLL;Factor DC;Allan KC;Barbar L;Jain T;Douvaras P;Fossati V;Miller RH;Tesar PJ
通讯作者：
Tesar PJ
影响因子：
48
作者：
Chetty, Sundari;Pagliuca, Felicia Walton;Honore, Christian;Kweudjeu, Anastasie;Rezania, Alireza;Melton, Douglas A.
通讯作者：
Melton, Douglas A.