Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells.
Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells.
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DOI：
10.1016/j.stem.2013.04.008
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发表时间：
2013-05-02
期刊：
影响因子：
23.9
通讯作者：
Studer, Lorenz
中科院分区：
文献类型：
--
作者：
Maroof, Asif M.;Keros, Sotirios;Tyson, Jennifer A.;Ying, Shui-Wang;Ganat, Yosif M.;Merkle, Florian T.;Liu, Becky;Goulburn, Adam;Stanley, Edouard G.;Elefanty, Andrew G.;Widmer, Hans Ruedi;Eggan, Kevin;Goldstein, Peter A.;Anderson, Stewart A.;Studer, Lorenz
人类多能干细胞（hPSC）是模拟大脑发育和疾病的有力工具。人类皮层由两个主要的神经元群组成，投射神经元和局部中间神经元。皮质中间神经元包括表达神经递质GABA的多种细胞类型。皮质中间神经元的功能障碍与神经精神疾病有关，包括精神分裂症、自闭症和癫痫。在这里，我们证明了在NKX2.1：：GFP hESC报告细胞系中高效衍生人皮质中间神经元。操纵SHH激活的时间产生三种不同的GFP+群体，具有特定的转录谱、神经递质表型和迁移行为。在鼠皮层环境中的进一步分化产生小清蛋白和生长抑素表达神经元，其表现出皮层中间神经元的突触输入和电生理特性。我们的研究定义了足以在体外模拟人类腹侧前脑发育的信号，并为研究皮质中间神经元参与人类疾病病理奠定了基础。
Human pluripotent stem cells (hPSCs) are a powerful tool for modeling brain development and disease. The human cortex is composed of two major neuronal populations, projection neurons and local interneurons. Cortical interneurons comprise a diverse class of cell types expressing the neurotransmitter GABA. Dysfunction of cortical interneurons has been implicated in neuropsychiatric diseases, including schizophrenia, autism and epilepsy. Here we demonstrate the highly efficient derivation of human cortical interneurons in a NKX2.1::GFP hESC reporter line. Manipulating the timing of SHH activation yields three distinct GFP+ populations with specific transcriptional profiles, neurotransmitter phenotypes and migratory behaviors. Further differentiation in a murine cortical environment yields parvalbumin and somatostatin expressing neurons that exhibit synaptic inputs and electrophysiological properties of cortical interneurons. Our study defines the signals sufficient to model human ventral forebrain development in vitro and lays the foundation for studying cortical interneuron involvement in human disease pathology.
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影响因子：
23.9
作者：
Fasano CA;Chambers SM;Lee G;Tomishima MJ;Studer L
通讯作者：
Studer L
影响因子：
64.8
作者：
Kriks, Sonja;Shim, Jae-Won;Piao, Jinghua;Ganat, Yosif M.;Wakeman, Dustin R.;Xie, Zhong;Carrillo-Reid, Luis;Auyeung, Gordon;Antonacci, Chris;Buch, Amanda;Yang, Lichuan;Beal, M. Flint;Surmeier, D. James;Kordower, Jeffrey H.;Tabar, Viviane;Studer, Lorenz
通讯作者：
Studer, Lorenz
DOI：
10.1073/pnas.0900141106
发表时间：
2009-09-08
影响因子：
11.1
作者：
Baraban, Scott C.;Southwell, Derek G.;Alvarez-Buylla, Arturo
通讯作者：
Alvarez-Buylla, Arturo
影响因子：
64.8
作者：
Insel, Thomas R.
通讯作者：
Insel, Thomas R.
DOI：
10.1073/pnas.0404474101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Kelly, S;Bliss, TM;Steinberg, GK
通讯作者：
Steinberg, GK