Dose-related shifts in proteome and function of extracellular vesicles secreted by fetal neural stem cells following chronic alcohol exposure.
Dose-related shifts in proteome and function of extracellular vesicles secreted by fetal neural stem cells following chronic alcohol exposure.
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DOI：
10.1016/j.heliyon.2022.e11348
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发表时间：
2022-11
期刊：
影响因子：
4
通讯作者：
Miranda, Rajesh C.
中科院分区：
文献类型：
--
作者：
Chung, Dae D.;Pinson, Marisa R.;Mahnke, Amanda H.;Salem, Nihal A.;Le, Khang T.;Payne, Elizabeth A.;Lehman, Tenley E.;Weintraub, Susan T.;Miranda, Rajesh C.
关键词：
越来越多的证据表明，细胞外囊泡（EVs）介导内分泌功能和乙醇等神经发育干扰物的致病作用。我们对体外培养的胎儿小鼠大脑皮质神经干细胞（NSCs）分泌的ev进行了质谱分析，以确定相对于对照组亲本NSCs，以及亲本NSCs暴露于一定剂量的乙醇后ev中过度代表的蛋白质和信号通路。EV蛋白质组与亲本NSCs有很大不同，尽管EV将蛋白质隔离在亚细胞区室中，但它们富含不同的形态发生信号，包括平面细胞极性途径。乙醇暴露有利于ev中的选择性蛋白质隔离和亲本NSCs的消耗，也导致ev中细胞周期和DNA复制途径的剂量无关的过度表达，以及rRNA加工和mTor应激途径的剂量依赖的过度表达。将未经处理的ev转移到naïve细胞导致氧化代谢和s期下降，而乙醇处理的NSCs衍生的ev则表现出减弱的作用。总的来说，这些数据表明，NSCs分泌的ev具有独特的蛋白质组，可能对受体细胞具有一般的生长抑制作用。此外，虽然乙醇导致蛋白质从NSCs选择性转移到电动汽车，但这些暴露衍生的电动汽车的功效减弱。产前酒精暴露；胎儿酒精谱系障碍；细胞外囊泡;神经干细胞；发展;蛋白质组;外来体;酒精;性;WGCNA。
Accumulating evidence indicates that extracellular vesicles (EVs) mediate endocrine functions and also pathogenic effects of neurodevelopmental perturbagens like ethanol. We performed mass-spectrometry on EVs secreted by fetal murine cerebral cortical neural stem cells (NSCs), cultured ex-vivo as sex-specific neurosphere cultures, to identify overrepresented proteins and signaling pathways in EVs relative to parental NSCs in controls, and following exposure of parental NSCs to a dose range of ethanol. EV proteomes differ substantially from parental NSCs, and though EVs sequester proteins across sub-cellular compartments, they are enriched for distinct morphogenetic signals including the planar cell polarity pathway. Ethanol exposure favored selective protein sequestration in EVs and depletion in parental NSCs, and also resulted in dose-independent overrepresentation of cell-cycle and DNA replication pathways in EVs as well as dose-dependent overrepresentation of rRNA processing and mTor stress pathways. Transfer of untreated EVs to naïve cells resulted in decreased oxidative metabolism and S-phase, while EVs derived from ethanol-treated NSCs exhibited diminished effect. Collectively, these data show that NSCs secrete EVs with a distinct proteome that may have a general growth-inhibitory effect on recipient cells. Moreover, while ethanol results in selective transfer of proteins from NSCs to EVs, the efficacy of these exposure-derived EVs is diminished. Prenatal alcohol exposure; Fetal alcohol spectrum disorder; Extracellular vesicle; Neural stem cell; Developmental; Proteome; Exosome; Alcohol; Sex; WGCNA.
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影响因子：
7.3
作者：
Adamo, Annalisa;Brandi, Jessica;Krampera, Mauro
通讯作者：
Krampera, Mauro
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
影响因子：
2.8
作者：
Anthony, Bruce;Zhou, Feng C.;Ruiz, Joseph
通讯作者：
Ruiz, Joseph
影响因子：
19
作者：
Dalton S
通讯作者：
Dalton S
影响因子：
5.1
作者：
CLARREN, SK;ALVORD, EC;SMITH, DW
通讯作者：
SMITH, DW