基因组编辑揭示了OCT4在人类胚胎形成中的作用
Norah M E Fogarty1, Afshan McCarthy1, Kirsten E Snijders2
1Human Embryo and Stem Cell Laboratory, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
Nature
|September 28, 2017
概括
CRISPR-Cas9基因组编辑揭示了OCT4对人类胚胎细胞发育至关重要. 人类胚胎中的OCT4 (POU5F1) 基因编辑破坏了细胞命运,影响了 trofhectoderm 和 epiblast 基因表达.
科学领域:
- 发育生物学
- 遗传学
- 干细胞生物学
背景情况:
- 人类胚胎发生过程中的初始细胞命运决定至关重要,
- 转录因子OCT4在多能性和早期发育中起着关键作用.
研究的目的:
- 使用CRISPR-Cas9基因组编辑来研究OCT4在人类胚胎形成中的功能.
- 改进有效的基因向方法.
主要方法:
- 使用CRISPR-Cas9基因组编辑来向双胞胎人类的POU5F1基因 (编码OCT4).
- 使用人类胚胎干细胞和小鼠胞胎微注射,确定了有效的OCT4导向RNA.
- 对POU5F1- null人类细胞进行了转录组学分析.
主要成果:
- 针对人体胚胎细胞中的POU5F1影响了胚胎细胞的发育.
- 人类POU5F1-null细胞表现出皮体 (例如CDX2) 和表皮体 (例如NANOG) 基因的下调表达.
- Pou5f1-null小鼠胚胎显示出受损的,但未被废除的,胚胎细胞发育和基因表达.
结论:
- CRISPR-Cas9基因组编辑对于研究人类发育中的基因功能是有效的.
- 在人类胚胎中,OCT4对于胚胎的正常发育和细胞命运决定至关重要.
- 在人类发育中的OCT4的作用不同于在小鼠发育中的作用.
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