通过ESRB的双边功能,可以随着时间的推移整合信号,以平衡自我更新和差异化
Teresa E Knudsen1, William B Hamilton1, Martin Proks1
1The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), University of Copenhagen, Copenhagen, Denmark.
Cell systems
|August 26, 2023
概括
像NANOG和ESRRB这样的转录因子 (TF) 协同结合DNA以保持干细胞多能性. 它们的联合作用,而不仅仅是单个作用,决定了细胞的身份,并保护了发育的可塑性.
科学领域:
- 发展生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 分子生物学分子生物学
背景情况:
- 纯粹的小鼠胚胎干细胞 (ESC) 具有无限的多能性.
- 转录因子 (TFs) 整合细胞背景以进行细胞特异化.
- 众所周知,多能因子NANOG和ESRRB可以共同结合DNA.
研究的目的:
- 调查多能性TF是否直接支持多能状态,或是从组合作用中产生的.
- 阐明ESRB在多能维护和差异化中的作用.
- 了解TF体积测量如何影响细胞命运决策.
主要方法:
- 在ESC中对NANOG和ESRB的共同表达分析.
- 评估ESRB在存在或缺少NANOG时的功能.
- 在二方ESRB活动的模型.
主要成果:
- 当与NANOG联合表达时,ESRRB支持多能性.
- 在没有NANOG的情况下,ESRRB促进了原始的内皮身份.
- NANOG与ESRB的比率量化控制了差异化.
- 在形模型表明ESRB保障差异化可塑性.
结论:
- 合作型TF的组合作用,如NANOG和ESRRB,对于保持干细胞多能性至关重要.
- TF体积测量允许对细胞命运决定进行定量控制,维持中间身份.
- 这种机制使不朽干细胞能够在体外扩张,并保证了发育性可塑性.
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