Cross-species comparative analysis of single presynapses.

Cross-species comparative analysis of single presynapses.
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DOI:
10.1038/s41598-023-40683-8
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发表时间:
2023-08-24
期刊:
影响因子:
4.6
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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比较不同物种和地区的大脑结构可以获得关键的功能见解。利用一种新的基于质谱的方法,飞行时间突触测定法(SynTOF)的公开数据,我们应用了一种无监督的机器学习方法,对三个物种和三个大脑区域的突触前分子丰度进行了比较研究。我们使用神经网络及其吸引人的特性来建模高维数据之间的复杂关系,以开发一个统一的无监督框架,用于比较正常人类,猕猴和小鼠样本中超过450万个单突触前的轮廓。一个广泛的验证表明,使用SynTOF分析进行跨物种比较的可行性。对20种突触前蛋白质丰度的综合分析显示,灵长类动物和小鼠之间几乎完全分离,涉及突触修剪、细胞能量、脂质代谢和神经传递。此外,我们的分析揭示了人类和猕猴的大脑皮层和新纹状体的突触前组成之间的强烈重叠。我们独特的方法阐明了突触前分子组成的物种和区域特异性变化。
Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 presynaptic proteins revealed near-complete separation between primates and mice involving synaptic pruning, cellular energy, lipid metabolism, and neurotransmission. In addition, our analysis revealed a strong overlap between the presynaptic composition of human and macaque in the cerebral cortex and neostriatum. Our unique approach illuminates species- and region-specific variation in presynapse molecular composition.
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