Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence.
Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence.
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DOI：
10.1016/j.neuron.2017.06.029
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发表时间：
2017-08-02
期刊：
影响因子：
16.2
通讯作者：
Khakh BS
中科院分区：
文献类型：
--
作者：
Chai H;Diaz-Castro B;Shigetomi E;Monte E;Octeau JC;Yu X;Cohn W;Rajendran PS;Vondriska TM;Whitelegge JP;Coppola G;Khakh BS
星形胶质细胞在大脑中普遍存在，并且被广泛认为在很大程度上是相同的。然而，这一观点尚未得到充分验证，星形胶质细胞是神经回路特化的可能性在很大程度上仍未被探索。在这里，我们使用多种综合方法，包括RNA-Seq，质谱，电生理，免疫组织化学，连续块面扫描电镜，形态学重建，药物遗传学，以及扩散染料，钙和谷氨酸成像，直接比较相同条件下成人纹状体和海马星形胶质细胞。我们发现纹状体和海马星形胶质细胞在电生理特性、Ca2+信号、形态和星形胶质细胞-突触接近性方面存在显著差异。对主动翻译RNA和蛋白质组学数据的无偏评价证实了海马和纹状体回路之间显著的星形胶质细胞多样性。因此，我们报告了星形胶质细胞的核心特性，揭示了神经回路中特化星形胶质细胞的证据，并提供了新的、综合的数据库资源和方法来探索成人大脑中星形胶质细胞的多样性和功能。Khakh实验室使用最先进的光学、解剖学、电生理学、转录组学和蛋白质组学方法来探索两种神经回路中星形胶质细胞的相似性和差异性。对十种方法的数据进行坦诚的评估，为星形胶质细胞多样性提供了强有力的证据，并为探索整个大脑的星形胶质细胞多样性提供了一个实验工作流程。
Astrocytes are ubiquitous in the brain and are widely held to be largely identical. However, this view has not been fully tested and the possibility that astrocytes are neural circuit-specialized remains largely unexplored. Here, we used multiple, integrated approaches including RNA-Seq, mass spectrometry, electrophysiology, immunohistochemistry, serial block-face scanning electron microscopy, morphological reconstructions, pharmacogenetics, as well as diffusible dye, calcium and glutamate imaging, to directly compare adult striatal and hippocampal astrocytes under identical conditions. We found significant differences between striatal and hippocampal astrocytes in electrophysiological properties, Ca2+ signaling, morphology and astrocyte-synapse proximity. Unbiased evaluation of actively translated RNA and proteomic data confirmed significant astrocyte diversity between hippocampal and striatal circuits. We thus report core astrocyte properties, reveal evidence for specialized astrocytes within neural circuits and provide new, integrated database resources and approaches to explore astrocyte diversity and function throughout the adult brain. The Khakh lab used state-of-the-art optical, anatomical, electrophysiological, transcriptomic and proteomic approaches to explore astrocyte similarities and differences in two neural circuits. Candid evaluation of the data across ten approaches provided strong evidence for astrocyte diversity and provided an experimental workflow to explore astrocyte diversity across the brain.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
16.2
作者：
Haustein MD;Kracun S;Lu XH;Shih T;Jackson-Weaver O;Tong X;Xu J;Yang XW;O'Dell TJ;Marvin JS;Ellisman MH;Bushong EA;Looger LL;Khakh BS
通讯作者：
Khakh BS
影响因子：
5.3
作者：
Jiang, Ruotian;Diaz-Castro, Blanca;Khakh, Baljit S.
通讯作者：
Khakh, Baljit S.
影响因子：
2.5
作者：
Fiala, JC;Kirov, SA;Harris, KM
通讯作者：
Harris, KM