Targeted Differentiation of Regional Ventral Neuroprogenitors and Related Neuronal Subtypes from Human Pluripotent Stem Cells.
Targeted Differentiation of Regional Ventral Neuroprogenitors and Related Neuronal Subtypes from Human Pluripotent Stem Cells.
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人多能干细胞定向分化区域腹侧神经祖细胞和相关神经元亚型
DOI：
10.1016/j.stemcr.2016.09.003
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发表时间：
2016-11-08
影响因子：
5.9
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Chi L;Fan B;Zhang K;Du Y;Liu Z;Fang Y;Chen Z;Ren X;Xu X;Jiang C;Li S;Ma L;Gao L;Liu L;Zhang X
胚状体（EB）形成和贴壁培养（AD）模式被认为同样适用于人类多能干细胞的神经规范。在这里，我们报道了在EB条件下，音刺猬诱导的腹侧神经祖细胞被注定为内侧神经节隆起（MGE），而AD细胞大多采用底板（FP）命运。EB-MGE随后分化为GABA和胆碱能神经元，而AD-FP倾向于多巴胺能神经元。AD和EB细胞不同的发育、代谢和粘附特性可能解释了它们不同的模式效力。基因靶向结合小分子筛选实验发现，在AD条件下，同时抑制wnt、STAT3和p38通路（3i）可以在很大程度上将FP转化为MGE。因此，分化范式和信号调节因子可以整合在一起，以指定不同的神经元亚型，用于研究和治疗相关的神经系统疾病，如癫痫、阿尔茨海默病和帕金森病。EB和AD模式在SHH模式下产生FP来源的DA神经元在AD条件下在SHH模式下产生Wnts/STAT3/p38抑制有利于在AD条件下形成MGE来源的GABA和CHAT神经元在EB或AD/3i条件下产生MGE来源的GABA和CHAT神经元在这篇文章中，Zhang, Liu， Gao和同事发现在EB条件下sh诱导的腹侧神经祖细胞被决定为MGE，而AD细胞被决定为FP。wnt /STAT3/p38通路与MGE和FP规范密切相关。因此，无论是MGE还是FP起源的GABA、胆碱能和多巴胺能神经元都可以通过适当的分化范式和信号调节因子的整合而产生。
Embryoid body (EB) formation and adherent culture (AD) paradigms are equivalently thought to be applicable for neural specification of human pluripotent stem cells. Here, we report that sonic hedgehog-induced ventral neuroprogenitors under EB conditions are fated to medial ganglionic eminence (MGE), while the AD cells mostly adopt a floor-plate (FP) fate. The EB-MGE later on differentiates into GABA and cholinergic neurons, while the AD-FP favors dopaminergic neuron specification. Distinct developmental, metabolic, and adhesion traits in AD and EB cells may potentially account for their differential patterning potency. Gene targeting combined with small-molecule screening experiments identified that concomitant inhibition of Wnts, STAT3, and p38 pathways (3i) could largely convert FP to MGE under AD conditions. Thus, differentiation paradigms and signaling regulators can be integrated together to specify distinct neuronal subtypes for studying and treating related neurological diseases, such as epilepsy, Alzheimer's disease, and Parkinson's disease. EB and AD paradigms yield different ventral neuroprogenitors upon SHH patterning DA neurons of FP origin are generated in AD conditions upon SHH patterning Wnts/STAT3/p38 inhibition benefits MGE specification under AD conditions GABA and CHAT neurons of MGE origin are generated in EB or AD/3i conditions In this article, Zhang, Liu, Gao, and colleagues show that SHH-induced ventral neuroprogenitors under EB conditions are fated to MGE, while the AD cells are fated to FP. Wnts/STAT3/p38 pathways are closely involved in MGE and FP specification. GABA, cholinergic, and dopaminergic neurons of either MGE or FP origin could therefore be generated through integration of appropriate differentiation paradigms and signaling regulators.
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影响因子：
46.9
作者：
通讯作者：
--
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
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Studer, Lorenz
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影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
23.9
作者：
Longmire, Tyler A.;Ikonomou, Laertis;Hawkins, Finn;Christodoulou, Constantina;Cao, Yuxia;Jean, J. C.;Kwok, Letty W.;Mou, Hongmei;Rajagopal, Jayaraj;Shen, Steven S.;Dowton, Anne A.;Serra, Maria;Weiss, Daniel J.;Green, Michael D.;Snoeck, Hans-Willem;Ramirez, Maria I.;Kotton, Darrell N.
通讯作者：
Kotton, Darrell N.
影响因子：
16.6
作者：
Du, Zhong-Wei;Chen, Hong;Liu, Huisheng;Lu, Jianfeng;Qian, Kun;Huang, CindyTzu-Ling;Zhong, Xiaofen;Fan, Frank;Zhang, Su-Chun
通讯作者：
Zhang, Su-Chun