Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.
Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits.
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DOI：
10.1038/nbt.2565
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发表时间：
2013-05
影响因子：
46.9
通讯作者：
中科院分区：
文献类型：
--
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基底前脑胆碱能神经元（BFCNs）和源自内侧神经节隆起（MGE）的γ - 氨基丁酸（GABA）中间神经元的功能障碍与学习和记忆障碍有关。在此我们提出一种将人胚胎干细胞（hESCs）分化为近乎均一的NKX2.1⁺ MGE样祖细胞群的方法。在将BFCNs和内侧隔区的一些GABA神经元被mu P75 - 皂草素破坏的小鼠海马体中进行移植后，人MGE样祖细胞（而非腹侧脊髓祖细胞）产生了与内源性神经元形成突触连接的BFCNs，而两种祖细胞都产生了相似的GABA神经元群。移植了MGE样祖细胞而非脊髓祖细胞的小鼠在学习和记忆缺陷方面有所改善。这些结果表明，MGE样祖细胞的后代，特别是BFCNs，对学习和记忆有贡献。我们的研究结果支持在开发治疗学习和记忆神经障碍的疗法中使用人干细胞衍生的MGE样祖细胞的前景。
Dysfunction of basal forebrain cholinergic neurons (BFCNs) and γ-aminobutyric acid (GABA) interneurons, derived from medial ganglionic eminence (MGE), is implicated in disorders of learning and memory. Here we present a method for differentiating human embryonic stem cells (hESCs) to a nearly uniform population of NKX2.1+ MGE-like progenitor cells. After transplantation into the hippocampus of mice in which BFCNs and some GABA neurons in the medial septum had been destroyed by mu P75-saporin, human MGE-like progenitors, but not ventral spinal progenitors, produced BFCNs that synaptically connected with endogenous neurons, whereas both progenitors generated similar populations of GABA neurons. Mice transplanted with MGE-like but not spinal progenitors showed improvements in learning and memory deficits. These results suggest that progeny of the MGE-like progenitors, particularly BFCNs, contributed to learning and memory. Our findings support the prospect of using human stem cell–derived MGE-like progenitors in developing therapies for neurological disorders of learning and memory.
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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.0808488105
发表时间：
2008-10-28
影响因子：
11.1
作者：
Aubry, Laetitia;Bugi, Aurore;Perrier, Anselme L.
通讯作者：
Perrier, Anselme L.
影响因子：
46.9
作者：
Lee, SH;Lumelsky, N;McKay, RD
通讯作者：
McKay, RD
影响因子：
5.3
作者：
Danjo, Teruko;Eiraku, Mototsugu;Sasai, Yoshiki
通讯作者：
Sasai, Yoshiki
影响因子：
5.3
作者：
Flames, Nuria;Pla, Ramon;Marin, Oscar
通讯作者：
Marin, Oscar