Astrocyte ethanol exposure reveals persistent and defined calcium response subtypes and associated gene signatures.
Astrocyte ethanol exposure reveals persistent and defined calcium response subtypes and associated gene signatures.
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DOI：
10.1016/j.jbc.2022.102147
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发表时间：
2022-08
影响因子：
4.8
通讯作者：
Sul, Jai-Yoon
中科院分区：
文献类型：
--
作者：
Kim, Hyun-Bum;Lu, Youtao;Oh, Seonkyung C.;Morris, Jacqueline;Miyashiro, Kevin;Kim, Junhyong;Eberwine, James;Sul, Jai-Yoon
星形胶质细胞在大脑功能中起着关键作用，但它们在乙醇(Etoh)消耗过程中的作用仍未得到很大程度的研究。根据最近关于星形胶质细胞生理学和基因表达异质性的研究结果，有能力识别亚型并捕捉这种异质性的方法是必要的。在这里，我们结合钙信号和基因表达的测量来确定乙醇诱导的星形胶质细胞亚型。在没有已证实的乙醇受体的情况下，乙醇被认为对许多受体的功能和下游的生物级联反应钙反应有影响。乙醇诱导钙信号转导的机制尚不清楚，这项研究为理解显示这些观察到的反应的细胞特征提供了第一步。为了表征潜在的星形胶质细胞亚型，我们评估了钙信号和星形胶质细胞对乙醇反应的基因表达特征之间的相关性。我们发现，不同剂量的乙醇增加了星形胶质细胞亚群的细胞内钙水平，根据反应波形特性区分出三种细胞反应类型和一种无反应亚型。此外，来自不同反应类型的星形胶质细胞的单细胞RNA-seq分析确定了类型丰富的歧视性基因表达特征。结合单细胞钙反应和基因表达分析，确定了星形胶质细胞群体中特定的星形胶质细胞亚群，这些亚群是由他们对乙醇的反应定义的。这一结果为确定星形胶质细胞对乙醇的敏感性与相应的钙信号和基因表达的可测量标记物之间的关系提供了基础，这将有助于研究星形胶质细胞对乙醇在脑内暴露的生理和病理的潜在的亚群特异性影响。
Astrocytes play a critical role in brain function, but their contribution during ethanol (EtOH) consumption remains largely understudied. In light of recent findings on the heterogeneity of astrocyte physiology and gene expression, an approach with the ability to identify subtypes and capture this heterogeneity is necessary. Here, we combined measurements of calcium signaling and gene expression to define EtOH-induced astrocyte subtypes. In the absence of a demonstrated EtOH receptor, EtOH is believed to have effects on the function of many receptors and downstream biological cascades that underlie calcium responsiveness. This mechanism of EtOH-induced calcium signaling is unknown and this study provides the first step in understanding the characteristics of cells displaying these observed responses. To characterize underlying astrocyte subtypes, we assessed the correlation between calcium signaling and astrocyte gene expression signature in response to EtOH. We found that various EtOH doses increased intracellular calcium levels in a subset of astrocytes, distinguishing three cellular response types and one nonresponsive subtype as categorized by response waveform properties. Furthermore, single-cell RNA-seq analysis of astrocytes from the different response types identified type-enriched discriminatory gene expression signatures. Combining single-cell calcium responses and gene expression analysis identified specific astrocyte subgroups among astrocyte populations defined by their response to EtOH. This result provides a basis for identifying the relationship between astrocyte susceptibility to EtOH and corresponding measurable markers of calcium signaling and gene expression, which will be useful to investigate potential subgroup-specific influences of astrocytes on the physiology and pathology of EtOH exposure in the brain.
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产前酒精暴露后小鼠 Igf2 基因座 DNA 甲基化和基因表达略有下降：甲基补充饮食的影响。
影响因子：
2.3
作者：
Downing, Chris;Johnson, Thomas E.;Larson, Colin;Leakey, Tatiana I.;Siegfried, Rachel N.;Rafferty, Tonya M.;Cooney, Craig A.
通讯作者：
Cooney, Craig A.
影响因子：
3.7
作者：
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Sarkar DK
影响因子：
16.6
作者：
Batiuk, Mykhailo Y.;Martirosyan, Araks;Holt, Matthew G.
通讯作者：
Holt, Matthew G.
DOI：
10.1126/science.aad7038
发表时间：
2016-08-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Habib N;Li Y;Heidenreich M;Swiech L;Avraham-Davidi I;Trombetta JJ;Hession C;Zhang F;Regev A
通讯作者：
Regev A
影响因子：
4.8
作者：
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通讯作者：
Guidotti, Alessandro