Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization.
Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization.
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DOI：
10.3390/cells11091411
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发表时间：
2022-04-21
期刊：
影响因子：
6
通讯作者：
Keung, Albert J.
中科院分区：
文献类型：
--
作者：
Tam, Ryan W.;Keung, Albert J.
关键词：
对重复刺激的基因脱敏反应是一种复杂的表型，在包括成瘾、学习和记忆在内的稳态和疾病过程中都很重要。这些复杂的表型在啮齿动物系统中被表征并与重要的生理相关功能联系在一起，但在人类模型中很难捕捉到，因为人类对重要神经递质的急性反应尚未得到充分研究。通过转录组学分析，我们绘制了人类干细胞衍生的培养基棘神经元样细胞（hsmn样细胞）对多巴胺的动态反应。此外，我们表明这些人类神经元可以反映和捕获细胞对慢性和急性多巴胺管理的脱敏。这些人类细胞进一步能够捕捉复杂的受体串扰，以响应不同多巴胺受体亚型的药理学扰动。这项研究证明了利用人类干细胞来源的神经元来捕获和研究大脑复杂的动态机制的潜在效用和仍然存在的挑战。
Gene desensitization in response to a repeated stimulus is a complex phenotype important across homeostatic and disease processes, including addiction, learning, and memory. These complex phenotypes are being characterized and connected to important physiologically relevant functions in rodent systems but are difficult to capture in human models where even acute responses to important neurotransmitters are understudied. Here through transcriptomic analysis, we map the dynamic responses of human stem cell-derived medium spiny neuron-like cells (hMSN-like cells) to dopamine. Furthermore, we show that these human neurons can reflect and capture cellular desensitization to chronic versus acute administration of dopamine. These human cells are further able to capture complex receptor crosstalk in response to the pharmacological perturbations of distinct dopamine receptor subtypes. This study demonstrates the potential utility and remaining challenges of using human stem cell-derived neurons to capture and study the complex dynamic mechanisms of the brain.
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影响因子：
4.7
作者：
Diana M
通讯作者：
Diana M
DOI：
10.1073/pnas.89.13.5764
发表时间：
1992-07-01
影响因子：
11.1
作者：
HOPE, B;KOSOFSKY, B;NESTLER, EJ
通讯作者：
NESTLER, EJ
影响因子：
2.2
作者：
Grigor'eva, Elena, V;Malankhanova, Tuyana B.;Malakhova, Anastasia A.
通讯作者：
Malakhova, Anastasia A.
影响因子：
8.8
作者：
Iannielli, Angelo;Ugolini, Giovanni Stefano;Broccoli, Vania
通讯作者：
Broccoli, Vania
影响因子：
25
作者：
Heller, Elizabeth A.;Cates, Hannah M.;Pena, Catherine J.;Sun, Haosheng;Shao, Ningyi;Feng, Jian;Golden, Sam A.;Herman, James P.;Walsh, Jessica J.;Mazei-Robison, Michelle;Ferguson, Deveroux;Knight, Scott;Gerber, Mark A.;Nievera, Christian;Han, Ming-Hu;Russo, Scott J.;Tamminga, Carol S.;Neve, Rachael L.;Shen, Li;Zhang, H. Steve;Zhang, Feng;Nestler, Eric J.
通讯作者：
Nestler, Eric J.