在Oct4和Sox2目标中的异质性在4细胞小鼠胚胎中的细胞命运偏差
Mubeen Goolam1, Antonio Scialdone2, Sarah J L Graham1
1Department of Physiology, Development & Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK.
Cell
|March 26, 2016
概括
在小鼠胚胎中早期异质基因表达,特别是涉及Sox21,启动细胞命运决策. 这一过程平衡了多能性和差异化,
科学领域:
- 发育生物学
- 遗传学
- 表观遗传学
背景情况:
- 植入前的发育对于确定哺乳动物的胚胎和胚胎外细胞命运至关重要.
- 了解细胞命运决定在早期发育过程中的启动是必不可少的.
研究的目的:
- 研究小鼠植入前发育过程中细胞命运的时间和机制.
- 描述基因表达异质性在这些决定启动中的作用.
主要方法:
- 在小鼠植入前发育过程中对所有细胞的单细胞转录组分析.
- 使用活细胞追踪来监测细胞系和后代.
- 多能性调节剂 (Oct4,Sox2) 和分化标记物的基因表达分析 (Cdx2).
- 涉及基因组H3R26-甲基酶CARM1的表观遗传调节的研究.
主要成果:
- 早在4细胞阶段就观察到多能性调节剂Oct4和Sox2的异质表达.
- Sox21表现出高度异质的表达,水平降低导致更多的胚胎外后代.
- 减少Sox21表达导致差异化调节器Cdx2的过早上调.
- Sox21表达水平由基因素H3R26-甲基酶CARM1调节,这表明了表观遗传的影响.
结论:
- 由4细胞阶段开始的异质基因表达在哺乳动物植入前发育过程中在细胞命运决定中发挥着基本作用.
- Sox21作为多能性的保障,其由CARM1的调节突显了表观遗传机制的重要性.
- 通过早期基因表达异质性调节多能性和分化之间的平衡是建立独特细胞系的关键.
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