ApoE通过微RNA和H3K27me3介导的抑制来维持神经元的完整性
Jiazi Tan1, Yow-Yong Tan1,2, Zhen-Kai Ngian1
1Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore.
iScience
|March 5, 2024
概括
在神经元分化过程中,Apolipoprotein E (ApoE) 防止非神经元细胞过度增殖. ApoE通过降解miR-199a-5p来维持神经元的完整性,通过H3K27me3.3调节基因表达.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 已知Apolipoprotein E (ApoE) 调节神经发生,但其在控制神经元发育过程中的遗传程序方面的确切作用尚不清楚.
- 现有的研究强调了ApoE在神经元过程中的参与,但其对基因表达的影响背后的机制在很大程度上仍未被阐明.
研究的目的:
- 研究ApoE在人类神经干细胞 (NSC) 分化成神经元的遗传调节中的作用.
- 阐明ApoE在神经发生过程中影响基因表达和细胞增殖的分子机制.
主要方法:
- 从同源控制和ApoE缺陷 (ApoE-/-) 人类NSC诱导皮质神经元.
- 转录组分析以比较基因表达特征与体内人类中脑数据.
- 在ApoE-/-细胞中研究微RNA (miR-199a-5p) 和表观遗传修饰 (H3K27me3).
- 对ApoE与miR-199a-5p的直接相互作用的评估.
主要成果:
- ApoE表达对于NSC分化并不重要,但在扩展培养中防止非神经元细胞过度增殖.
- ApoE缺乏导致miR-199a-5p升高,EZH1蛋白减少,H3K27me3表观遗传标记减少.
- 在ApoE-/- NPC中减少的H3K27me3与细胞外基因和血管生成基因的异常表达相关.
- ApoE编码序列直接抑制miR-199a-5p活动,独立于蛋白质翻译.
结论:
- ApoE通过针对目标的miRNA降解来调节miR-199a-5p水平来维持神经元完整性.
- 在神经元分化过程中,ApoE传递H3K27me3介导的非神经元基因抑制,防止异常细胞的增殖.
- 这些发现揭示了ApoE在控制神经发生和维持神经元恒温的新机制.
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