一个表观遗传障碍决定了人类神经元成熟的时间
Gabriele Ciceri1, Arianna Baggiolini2,3,4, Hyein S Cho2,5
1The Center for Stem Cell Biology and Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. cicerig@mskcc.org.
Nature
|January 31, 2024
概括
人类大脑的发育是缓慢的, 抑制像EZH2这样的特定因素可以加速神经元的成熟,
科学领域:
- 神经科学
- 发育生物学
- 表观遗传学
背景情况:
- 人类大脑的发育与其他物种相比显著延长.
- 皮层神经元的成熟是一个缓慢的过程,
- 这种缓慢的成熟保持在人类多能干细胞 (hPSC) 衍生的神经元中.
研究的目的:
- 确定控制人类神经元成熟时间的分子机制.
- 研究细胞内在因素在调节发育速度中的作用.
- 了解长期成熟的表观遗传基础.
主要方法:
- 在实验室中开发了基于hPSC的同步皮质神经元生产方法.
- 创建了一个神经元成熟的地图 (形态,功能,分子).
- 使用功能丧失和表观遗传因子的暂时抑制研究 (EZH2,EHMT1/2,DOT1L).
主要成果:
- 确定了一个特定的表观遗传发育程序, 决定了人类神经元的成熟时间.
- 观察到表观遗传因素限制了成熟程序的速度.
- 已经证明,在原始细胞中抑制表观遗传因子 (EZH2,EHMT1/2,DOT1L) 会导致神经元早成熟.
结论:
- 人类神经元成熟的速度是由原生细胞中建立的表观遗传屏障决定的.
- 这种屏障使转录程序保持平衡状态,并逐渐释放它们.
- 表观遗传调节对于人类皮层神经元发育的延长时间表至关重要.
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