Cdk8和Hira突变触发了X染色体在幼稚的雌性杂交小鼠胚胎干细胞中的消除
Kevin Halter1, Jingyi Chen1, Tadeas Priklopil2
1Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, Zurich, Switzerland.
概括
希拉和Cdk8基因的突变导致小鼠胚胎干细胞 (ESC) 快速失去X染色体. 这种染色体消除,而不是细胞选择,发生的速度很高,提供了一个新的系统来研究X染色体的不稳定性.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 发展生物学 发展生物学
背景情况:
- 小鼠胚胎干细胞 (ESC) 通常保持稳定的型.
- 雌性ESC经常失去X染色体,使X染色体失活的研究复杂化.
- 混合ESC可以通过维持两个X染色体来模拟X染色体不活化.
研究的目的:
- 研究混合ESC中X染色体损失的分子驱动因素.
- 建立一个系统来量化X染色体损失率.
- 阐明X染色体消除的机制.
主要方法:
- 在混合雌性ESC中产生联合Hira和Cdk8突变.
- 在原始介质中培养ESC以诱导X染色体损失.
- 测量染色体损失率,区分淘汰与选择.
- 评估Xist表达在染色体稳定中的作用.
主要成果:
- 结合的Hira和Cdk8突变会在混合ESC中诱导快速的X染色体损失.
- 在原始ESC培养中抑制MEK1足以导致X染色体损失.
- X染色体的损失通过染色体消除以每细胞分裂0.3%的速度发生.
- 在突变的ESC中,体表达拯救了X染色体的不稳定性.
结论:
- 希拉和Cdk8突变是X染色体消除的分子驱动因素.
- 描述了一种新的细胞系统,用于研究X染色体不稳定机制.
- 丢失X染色体是一个消除的过程,与选择不同.
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