Byumseok Koh, Young Eun Kim, Sung Bum Park, Seong Soon Kim, Jangjae Lee, Jeong Hyeon Jo, KyungJin Lee, Dong Hyuck Bae, Tae-Young Kim, Sung-Hee Cho*, Myung Ae Bae*, Dukjin Kang* and Ki Young Kim*,
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引用次数: 0
摘要
本研究采用多组学方法,利用脑器官组织研究钠通道蛋白1型亚基α(SCN1A)基因敲除(SCN1A KO)对大脑发育和功能的影响。通过全面的全局组学分析,我们发现在无基质分化条件下,与对照组相比,SCN1A KO 器官表现出生长下降、神经递质水平失调以及脂质组、蛋白质组和转录组特征的改变。神经化学分析揭示了关键神经递质水平的降低,脂质体分析则突显了醚磷脂和鞘磷脂的变化。此外,SCN1A KO类器官蛋白质组的定量分析显示胆固醇代谢和钠离子运输发生了紊乱,可能会影响突触传递。这些发现表明胆固醇代谢和钠离子转运失调,对突触传递有影响。总之,这些发现揭示了与 SCN1A 相关的疾病(如德拉沃综合征)的分子机制,并为治疗干预提供了潜在的途径。
Unraveling the Molecular Landscape of SCN1A Gene Knockout in Cerebral Organoids: A Multiomics Approach Utilizing Proteomics, Lipidomics, and Transcriptomics
This study investigates the impact of sodium channel protein type 1 subunit alpha (SCN1A) gene knockout (SCN1A KO) on brain development and function using cerebral organoids coupled with a multiomics approach. From comprehensive omics analyses, we found that SCN1A KO organoids exhibit decreased growth, dysregulated neurotransmitter levels, and altered lipidomic, proteomic, and transcriptomic profiles compared to controls under matrix-free differentiation conditions. Neurochemical analysis reveals reduced levels of key neurotransmitters, and lipidomic analysis highlights changes in ether phospholipids and sphingomyelin. Furthermore, quantitative profiling of the SCN1A KO organoid proteome shows perturbations in cholesterol metabolism and sodium ion transportation, potentially affecting synaptic transmission. These findings suggest dysregulation of cholesterol metabolism and sodium ion transport, with implications for synaptic transmission. Overall, these insights shed light on the molecular mechanisms underlying SCN1A-associated disorders, such as Dravet syndrome, and offer potential avenues for therapeutic intervention.
ACS OmegaChemical Engineering-General Chemical Engineering
CiteScore
6.60
自引率
4.90%
发文量
3945
审稿时长
2.4 months
期刊介绍:
ACS Omega is an open-access global publication for scientific articles that describe new findings in chemistry and interfacing areas of science, without any perceived evaluation of immediate impact.