在哺乳动物衰老过程中,全身细胞动态和表观基因组重塑
Ziyu Lu1,2, Zehao Zhang1,2, Zihan Xu1,2
1Laboratory of Single Cell Genomics and Population Dynamics, The Rockefeller University, New York, NY, USA.
概括
衰老导致21个小鼠组织细胞群的显著变化,由系统信号和内在/外在因素驱动. 这些与年龄相关的细胞变化通常取决于性别,影响表观基因组.
科学领域:
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 衰老是一个复杂的生物过程,其特点是细胞和生物的功能逐渐下降.
- 了解不同组织中衰老的细胞和分子基础对于开发干预措施至关重要.
- 表观基因组变化在与年龄相关的细胞变化中起着重要作用.
研究的目的:
- 在多个小鼠组织中构建一个全面的单细胞染色质可访问性老化图谱.
- 在衰老过程中识别整个生物体的细胞变化和表观基因组动态.
- 研究性别对与年龄相关的细胞和表观基因组变化的影响.
主要方法:
- 单细胞染色体可访问性测序 (scATAC-seq) 在21只小鼠组织上进行.
- 分析了三个年龄组和两性之间的数据,以确定细胞类型和亚型的人口转移.
- 进行了分子分析,以确定与年龄相关的细胞动态的内在和外在调节者.
主要成果:
- 大约四分之一的已识别的细胞类型和亚型显示出与年龄相关的显著人口变化.
- 从广泛分布的血统中观察到跨细胞状态的同步与年龄相关的动态,这表明有系统的衰老信号.
- 内在调节者 (染色质峰值,转录因子活性) 和外在因素 (细胞因子程序) 被确定为这些转变的驱动因素.
- ~40%的与衰老相关的人口动态取决于性别,有大量的性别特异性染色体变化.
结论:
- 衰老以系统性和性别依赖的方式对各种组织的染色质景观和细胞组成进行了深刻的重塑.
- 该研究提供了一个全面的框架,以了解单细胞分辨率的全生物体衰老动态.
- 这些发现强调了将性别视为衰老研究和治疗策略中的生物变量的重要性.
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