Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds.
Mapping Astrocyte Transcriptional Signatures in Response to Neuroactive Compounds.
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响应神经活性化合物的映射星形胶质细胞转录特征。
DOI：
10.3390/ijms22083975
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发表时间：
2021-04-12
影响因子：
5.6
通讯作者：
Deneen B
中科院分区：
文献类型：
--
作者：
Sardar D;Lozzi B;Woo J;Huang TW;Cvetkovic C;Creighton CJ;Krencik R;Deneen B
星形胶质细胞在正常的大脑功能中起着核心作用，是监督行为输出的突触网络的关键组成部分。尽管它们与神经元密切相关，但神经元源性信号如何在基因表达水平上影响星形胶质细胞功能仍然缺乏特征，这主要是由于与解剖神经元与星形胶质细胞特异性效应相关的困难。在这里，我们使用干细胞衍生的星形胶质细胞的体外系统，以确定基因表达谱的星形胶质细胞，神经元的影响和调节星形胶质细胞的发展。此外，我们表明，神经递质和神经调质诱导不同的转录组和染色质的可及性变化的星形胶质细胞是独特的每一个这些神经活性化合物。与谷氨酸、γ-氨基丁酸（GABA）、乙酰胆碱和5-羟色胺相比，去甲肾上腺素对星形胶质细胞的转录谱有更深远的影响，这一观察结果突出了这些发现。这通过体外增强的去甲肾上腺素诱导的转录组和染色质可及性变化以及体内增强的钙信号传导来证明。总之，我们的研究揭示了星形胶质细胞对神经元衍生的神经活性化合物反应的不同转录组和染色质结构特征。由于星形胶质细胞的功能在所有神经系统疾病中都会受到影响，因此这项研究为探索星形胶质细胞-神经元通讯的遗传机制提供了一个新的切入点，该机制可能在疾病中失调。
Astrocytes play central roles in normal brain function and are critical components of synaptic networks that oversee behavioral outputs. Despite their close affiliation with neurons, how neuronal-derived signals influence astrocyte function at the gene expression level remains poorly characterized, largely due to difficulties associated with dissecting neuron- versus astrocyte-specific effects. Here, we use an in vitro system of stem cell-derived astrocytes to identify gene expression profiles in astrocytes that are influenced by neurons and regulate astrocyte development. Furthermore, we show that neurotransmitters and neuromodulators induce distinct transcriptomic and chromatin accessibility changes in astrocytes that are unique to each of these neuroactive compounds. These findings are highlighted by the observation that noradrenaline has a more profound effect on transcriptional profiles of astrocytes compared to glutamate, gamma-aminobutyric acid (GABA), acetylcholine, and serotonin. This is demonstrated through enhanced noradrenaline-induced transcriptomic and chromatin accessibility changes in vitro and through enhanced calcium signaling in vivo. Taken together, our study reveals distinct transcriptomic and chromatin architecture signatures in astrocytes in response to neuronal-derived neuroactive compounds. Since astrocyte function is affected in all neurological disorders, this study provides a new entry point for exploring genetic mechanisms of astrocyte–neuron communication that may be dysregulated in disease.
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星形胶质细胞诱导的突触发生的分子机制。
影响因子：
5.7
作者：
Baldwin KT;Eroglu C
通讯作者：
Eroglu C
影响因子：
16.6
作者：
Batiuk, Mykhailo Y.;Martirosyan, Araks;Holt, Matthew G.
通讯作者：
Holt, Matthew G.
影响因子：
16.2
作者：
Corkrum, Michelle;Covelo, Ana;Araque, Alfonso
通讯作者：
Araque, Alfonso
影响因子：
16.2
作者：
Huang AY;Woo J;Sardar D;Lozzi B;Bosquez Huerta NA;Lin CJ;Felice D;Jain A;Paulucci-Holthauzen A;Deneen B
通讯作者：
Deneen B
系统的三维共培养迅速概括了人类神经元与星形胶质细胞之间的相互作用。
影响因子：
5.9
作者：
Krencik R;Seo K;van Asperen JV;Basu N;Cvetkovic C;Barlas S;Chen R;Ludwig C;Wang C;Ward ME;Gan L;Horner PJ;Rowitch DH;Ullian EM
通讯作者：
Ullian EM