在多能性期间,TRF2独立的染色体末端保护
Phil Ruis1, David Van Ly2,3, Valerie Borel1
1The Francis Crick Institute, London, UK.
Nature
|November 26, 2020
概括
多能干细胞和体组织之间的端粒保护有所不同. 与体细胞不同的是,TRF2蛋白在胚胎干细胞中是不可用的,而胚胎干细胞没有它就会形成T环.
科学领域:
- 细胞生物学
- 遗传学
- 发育生物学
背景情况:
- 哺乳动物的端粒通过shelterin复合体保护染色体末端.
- TRF2 (TERF2) 对于体细胞中的端粒保护至关重要,形成T环并防止端到端的融合.
- 在体细胞中TRF2的损失导致端粒脱保护,染色体融合和细胞死亡.
研究的目的:
- 研究TRF2在多能胚胎干细胞 (ES) 中的端粒保护作用.
- 将多能细胞与体细胞的端粒保护机制进行比较.
- 了解为什么在ES细胞中不需要TRF2.
主要方法:
- 在小鼠胚胎干细胞中删除TRF2.
- 对端粒完整性,DNA损伤反应和T环形成的分析.
- 对Trf2-null胚胎和脱离多能细胞的评估.
主要成果:
- 对于小鼠ES细胞的端粒保护,TRF2是不可或缺的,这些细胞在没有融合的情况下表现出减弱的DNA损伤反应.
- ES细胞独立于TRF2形成T环.
- 在非多能细胞中植入前的Trf2-null胚胎停滞.
- 脱离多能性的细胞迅速采用TRF2依赖的端粒保护.
结论:
- 在多能和体性哺乳动物组织中,端粒保护机制显著不同.
- 在分化细胞中,TRF2对于端粒末端的保护至关重要,但在多能干细胞中却不重要.
- ES细胞独立于TRF2形成T环的能力解释了多能性期间的可用性.
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