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在人类海马体的衰老过程中表观遗传和3D基因组重编程

Nathan R Zemke^1,2, Seoyeon Lee¹, Sainath Mamde¹

¹Department of Cellular and Molecular Medicine, University of California, San Diego School of Medicine; La Jolla, CA, USA.

bioRxiv : the preprint server for biology

|October 28, 2024

概括

老化的人类大脑显示显著的细胞损失和改变了海马中的基因调节,影响了认知功能. 这项研究揭示了与年龄相关的认知衰退相关的关键分子变化.

科学领域:

神经科学是一个神经科学.
基因组学就是基因组学.
衰老研究研究衰老研究

背景情况:

与年龄相关的认知衰退与海马体的变化有关.
大脑中与衰老相关的基因表达的调节机制尚未得到充分理解.

研究的目的:

研究人类海马体细胞类型,状态和基因调控特征的与年龄相关的变化.
提供关于人类衰老期间认知衰退的分子基础的见解.

主要方法:

生成单核基因表达,染色质可访问性,DNA甲基化和3D基因组数据.
在成年人一生中分析了40个人类海马体组织.
综合多原子数据,以识别与年龄相关的分子变化.

主要成果:

观察到随着衰老而显著减少的星体细胞,寡类细胞前体细胞 (OPC) 和内皮细胞.
鉴定了由表观遗传重编程驱动的微质中从恒常状态转变为炎症状态的切换.
在老年海马细胞中发现了3D基因组架构的侵蚀.

结论:

衰老会影响海马细胞的组成和功能,导致认知能力下降.
在微质中表观遗传和3D基因组重编程是大脑衰老的关键特征.
这项研究提供了老化的人类海马的多原子地图,揭示了关键的调节变化.

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