神经细胞的染色体可访问性动态揭示了老化期间神经干细胞粘附和迁移的缺陷
Robin W Yeo1, Olivia Y Zhou1,2,3, Brian L Zhong4
1Department of Genetics, Stanford University, Stanford, CA, USA.
Nature aging
|July 13, 2023
概括
衰老会损害神经干细胞 (NSC) 功能和大脑再生. 抑制ROCK可以恢复NSC迁移,并促进老年大脑的神经发生,提供一种潜在的治疗策略.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 老年学是一门学科.
背景情况:
- 大脑干细胞的再生能力随着年龄的增长而下降.
- 驱动神经干细胞 (NSC) 与年龄相关的衰退的机制尚不清楚.
研究的目的:
- 为了研究在衰老过程中神经性细胞中的全基因组染色质可访问性变化.
- 阐明这些变化对神经干细胞行为和神经发生的功能后果.
主要方法:
- 在体内全基因组染色质可访问性概况.
- 在神经干细胞的体外迁移试验.
- 使用张力传感器来测量细胞-细胞粘附力.
- 药理上抑制ROCK通路的作用.
主要成果:
- 衰老改变了染色体在粘附和迁移基因的可访问性,在静止和激活的NSC中不同.
- 激活的NSC随着年龄的增长显示了附着性和迁移的减少,这与细胞骨力量的增加有关.
- ROCK抑制逆转了与年龄相关的迁移缺陷,并在体内增强了神经发生.
结论:
- 衰老通过改变细胞骨调节来破坏神经干细胞的粘附和迁移.
- 准ROCK途径可以恢复NSC的迁移潜力,并改善老年大脑中的神经发生.
- 这些发现提供了对与年龄相关的认知衰退的治疗干预措施的见解.
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