TET1促进了早期人类血统的规范,包括生殖细胞
Fei-Man Hsu1,2,3, Qiu Ya Wu1, Emily B Fabyanic4,5
1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
iScience
|July 17, 2023
概括
十一转位1 (TET1) 促进了DNA脱甲基化和人类原始生殖细胞样细胞 (hPGCLC) 能力. hESC培养条件影响TET1
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 基因组学就是基因组学.
- 发展生物学 发展生物学
背景情况:
- 十一转位1 (TET1) 通过将5-甲基细胞因子 (5mC) 转化为5-基甲基细胞因子 (5hmC) 来催化DNA脱甲基化.
- 人类原始生殖细胞样细胞 (hPGCLCs) 对于研究早期生殖细胞发育和不孕症至关重要.
- 人类胚胎干细胞 (hESC) 培养条件可以影响细胞分化和表观遗传状态.
研究的目的:
- 调查DNA脱甲基化和TET1在hESCs的hPGCLC诱导中的作用.
- 在hPGCLC分化过程中分析表观遗传景观和基因调节.
- 确定hESC文化方法对hPGCLC能力的影响.
主要方法:
- 双硫酸盐辅助APOBEC合表观遗传测序 (bACEseq) 用于全基因组DNA甲基化分析.
- 使用CRISPR-Cas9基因编辑来评估TET1催化域的功能.
- 综合基因组学分析以将表观遗传修饰与基因表达和结合部位相关联.
主要成果:
- 在hPGCLC诱导过程中,5-基甲基 (5hmC) 在关键发育基因结合位点 (NANOG,SOX17,TFAP2C) 积累,与局部DNA脱甲基化相关.
- 删除TET1催化域会损害在小鼠胚胎纤维细胞上培养的hESC中的hPGCLC能力.
- 由TET1删除引起的hPGCLC能力缺陷在将hESC转移到定义的介质和重组基质时是可逆的.
结论:
- 5甲基细胞氨酸 (5hmC) 对于建立和维持人类原始生殖细胞类细胞 (hPGCLC) 能力至关重要.
- 人类胚胎干细胞 (hESC) 的培养环境显著调节TET1依赖的表观遗传调节和hPGCLC发育.
- 优化hESC培养条件对于高效和强大的hPGCLC诱导至关重要.
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