Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells.
Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells.
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DOI：
10.1016/j.scr.2013.05.002
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发表时间：
2013-09
影响因子：
1.2
通讯作者：
Chen, Gong
中科院分区：
文献类型：
--
作者：
Tang, Xin;Zhou, Li;Wagner, Alecia M.;Marchetto, Maria C. N.;Muotri, Alysson R.;Gage, Fred H.;Chen, Gong
来源于人诱导多能干细胞（hiPSC）的神经元已被用于模拟各种神经系统疾病。不同的方案已被用于将hiPSC分化为神经元，但它们的功能成熟过程在不同的研究中有很大差异。在这里，我们证明，层粘连蛋白，一种常用的基板iPSC的文化，是低效的，以促进hiPSC衍生的神经元的完全功能成熟。相反，星形胶质细胞基质大大加速了hiPSC衍生神经元的神经发育过程。将hiPSC衍生的神经祖细胞（hNPC）接种在层粘连蛋白或星形胶质细胞上后，我们监测了长达两个月的神经分化和成熟过程。我们发现，一个星期后铺板hNPC，有21倍以上的星形胶质细胞比层粘连蛋白的新分化的神经元。接种hNPC两周后，在星形胶质细胞上培养的神经元中的树突状分支比在层粘连蛋白上培养的神经元中的树突状分支多12倍。6周后，接种hNPC，Na+和K+电流，以及谷氨酸和GABA受体电流，在星形胶质细胞上培养的神经元比在层粘连蛋白上培养的神经元大3倍。接种hNPC两个月后，星形胶质细胞上培养的神经元自发突触事件是层粘连蛋白上培养的神经元的8倍。这些结果突出了星形胶质细胞在促进源自hiPSC的人神经元的神经分化和功能成熟中的关键作用。此外，我们的数据提供了培养中hiPSC衍生神经元的完整发育时间轴，为未来疾病建模和药物筛选研究提供了重要基准。
Neurons derived from human induced-pluripotent stem cells (hiPSCs) have been used to model a variety of neurological disorders. Different protocols have been used to differentiate hiPSCs into neurons, but their functional maturation process has varied greatly among different studies. Here, we demonstrate that laminin, a commonly used substrate for iPSC cultures, was inefficient to promote fully functional maturation of hiPSC-derived neurons. In contrast, astroglial substrate greatly accelerated neurodevelopmental processes of hiPSC-derived neurons. We have monitored the neural differentiation and maturation process for up to two months after plating hiPSC-derived neuroprogenitor cells (hNPCs) on laminin or astrocytes. We found that one week after plating hNPCs, there were 21-fold more newly differentiated neurons on astrocytes than on laminin. Two weeks after plating hNPCs, there were 12-fold more dendritic branches in neurons cultured on astrocytes than on laminin. Six weeks after plating hNPCs, the Na+ and K+ currents, as well as glutamate and GABA receptor currents, were 3-fold larger in neurons cultured on astrocytes than on laminin. And two months after plating hNPCs, the spontaneous synaptic events were 8-fold more in neurons cultured on astrocytes than on laminin. These results highlight a critical role of astrocytes in promoting neural differentiation and functional maturation of human neurons derived from hiPSCs. Moreover, our data presents a thorough developmental timeline of hiPSC-derived neurons in culture, providing important benchmarks for future studies on disease modeling and drug screening.
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影响因子：
64.8
作者：
Israel, Mason A.;Yuan, Shauna H.;Bardy, Cedric;Reyna, Sol M.;Mu, Yangling;Herrera, Cheryl;Hefferan, Michael P.;Van Gorp, Sebastiaan;Nazor, Kristopher L.;Boscolo, Francesca S.;Carson, Christian T.;Laurent, Louise C.;Marsala, Martin;Gage, Fred H.;Remes, Anne M.;Koo, Edward H.;Goldstein, Lawrence S. B.
通讯作者：
Goldstein, Lawrence S. B.
影响因子：
25
作者：
Ballas, Nurit;Lioy, Daniel T.;Grunseich, Christopher;Mandel, Gail
通讯作者：
Mandel, Gail
影响因子：
64.8
作者：
Itzhaki, Ilanit;Maizels, Leonid;Gepstein, Lior
通讯作者：
Gepstein, Lior
影响因子：
5.3
作者：
Jiang, Min;Chen, Gong
通讯作者：
Chen, Gong
DOI：
10.1073/pnas.1202922109
发表时间：
2012-04-10
影响因子：
11.1
作者：
Bilican, Bilada;Serio, Andrea;Chandran, Siddharthan
通讯作者：
Chandran, Siddharthan