The Drosophila brain on cocaine at single-cell resolution.
The Drosophila brain on cocaine at single-cell resolution.
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DOI：
10.1101/gr.268037.120
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发表时间：
2021-10
期刊：
影响因子：
7
通讯作者：
Anholt RRH
中科院分区：
文献类型：
--
作者：
Baker BM;Mokashi SS;Shankar V;Hatfield JS;Hannah RC;Mackay TFC;Anholt RRH
虽然可卡因对神经系统的影响已经有了很好的记录，但急性可卡因消费对整个大脑基因组基因表达的影响在很大程度上仍未被探索。这个问题在人类身上并不容易解决，但可以使用果蝇黑腹果蝇模型来解决，在这个模型中，可以同时调查整个大脑中的基因表达。暴露在可卡因中的苍蝇表现出运动活动受损，包括攀爬行为和惊吓反应(感觉运动整合的一种衡量标准)，癫痫发作和强迫梳理的发生率增加。为了确定对急性可卡因暴露有反应的特定细胞群，我们分析了两种果蝇样本中的单细胞转录反应，这些果蝇样本摄入了固定数量的蔗糖或补充了可卡因的蔗糖，无论性别。对总共86,224个细胞的转录图谱进行非监督聚类，产生了36个不同的聚类。基于基因标记的簇注释显示，所有主要细胞类型(神经元和神经胶质细胞)以及来自大多数大脑区域的神经递质类型都被呈现出来。大脑对可卡因的转录反应表现出深刻的性别二型性，男性比女性更明显。单个集群内的差异表达分析表明，集群对可卡因的反应是特定的。对应于蘑菇体和胶质细胞的Kenyon细胞的簇在可卡因暴露后显示出特别大的转录反应。簇特定的共表达网络和全球相互作用网络揭示了急性可卡因暴露影响的一系列不同的细胞过程。这些结果提供了一份模型大脑中由性二态可卡因调节的基因表达图谱。
Whereas the neurological effects of cocaine have been well documented, effects of acute cocaine consumption on genome-wide gene expression across the brain remain largely unexplored. This question cannot be readily addressed in humans but can be approached using the Drosophila melanogaster model, where gene expression in the entire brain can be surveyed at once. Flies exposed to cocaine show impaired locomotor activity, including climbing behavior and startle response (a measure of sensorimotor integration), and increased incidence of seizures and compulsive grooming. To identify specific cell populations that respond to acute cocaine exposure, we analyzed single-cell transcriptional responses in duplicate samples of flies that consumed fixed amounts of sucrose or sucrose supplemented with cocaine, in both sexes. Unsupervised clustering of the transcriptional profiles of a total of 86,224 cells yielded 36 distinct clusters. Annotation of clusters based on gene markers revealed that all major cell types (neuronal and glial) as well as neurotransmitter types from most brain regions were represented. The brain transcriptional responses to cocaine showed profound sexual dimorphism and were considerably more pronounced in males than females. Differential expression analysis within individual clusters indicated cluster-specific responses to cocaine. Clusters corresponding to Kenyon cells of the mushroom bodies and glia showed especially large transcriptional responses following cocaine exposure. Cluster specific coexpression networks and global interaction networks revealed a diverse array of cellular processes affected by acute cocaine exposure. These results provide an atlas of sexually dimorphic cocaine-modulated gene expression in a model brain.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.5
作者：
Davie K;Janssens J;Koldere D;De Waegeneer M;Pech U;Kreft Ł;Aibar S;Makhzami S;Christiaens V;Bravo González-Blas C;Poovathingal S;Hulselmans G;Spanier KI;Moerman T;Vanspauwen B;Geurs S;Voet T;Lammertyn J;Thienpont B;Liu S;Konstantinides N;Fiers M;Verstreken P;Aerts S
通讯作者：
Aerts S
影响因子：
3.7
作者：
Gibson SM;Ficklin SP;Isaacson S;Luo F;Feltus FA;Smith MC
通讯作者：
Smith MC
影响因子：
5.4
作者：
Badisa, Ramesh B.;Goodman, Carl B.;Fitch-Pye, Cheryl A.
通讯作者：
Fitch-Pye, Cheryl A.
影响因子：
64.5
作者：
Bainton, RJ;Tsai, LTY;Heberlein, U
通讯作者：
Heberlein, U