染色体可访问性 捐赠细胞的记忆 破坏牛体细胞核转移胚芽细胞的发展
Yuemeng Huang1,2, Jingcheng Zhang1,2, Xinmei Li3
1Key Laboratory of Animal Biotechnology of the Ministry of Agriculture, College of Veterinary Medicine, Northwest A&F University, Yangling, China.
概括
牛体细胞核转移 (SCNT) 显示,由于异常的基因调节,胚胎细胞的发育减少. 在SCNT胚胎中纠正异常色素可访问性改善了内部细胞质量的增殖,这表明BCL11B是提高SCNT效率的目标.
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.
- 发展生物学 发展生物学
- 生殖技术 生殖技术
背景情况:
- 牛体细胞核转移 (SCNT) 导致胚胎细胞的转移后发育能力降低.
- 基因表达调节异常在SCNT胚胎中的胚囊阶段被怀疑.
- 染色体可访问性是基因转录的关键调节者,在SCNT胚芽细胞中尚未得到充分研究.
研究的目的:
- 为了研究牛SCNT胚胎囊中的染色质可访问性.
- 为了确定SCNT胚胎中异常基因表达的原因.
- 探索改善SCNT效率的治疗目标.
主要方法:
- 对转化酶可访问的染色质的单细胞测序试验 (scATAC-seq) 在体内和SCNT胚芽细胞中进行.
- 伪素体分析被用来评估谱系分离和TF染色体可访问性动态.
- ATAC-seq和ChIP-seq是在SCNT供体细胞上进行的.
主要成果:
- 在SCNT胚囊中,表现出异常的染色体可访问性,对转录因子对于细胞内质量 (ICM) 发育至关重要.
- 在SCNT胚芽细胞的ICM中,失调的染色质可访问性动态与 H3K4me3丰富标志着捐赠细胞中持久的染色质可访问性记忆有关.
- 通过KDM5B对H3K4me3的脱甲基化纠正了异常色素的可访问性,降低了BCL11B的表达,并显著改善了SCNT胚胎囊中的ICM增殖.
结论:
- 在SCNT胚胎囊中的异常染色质可访问性与来自捐赠细胞的表观遗传记忆有关.
- BCL11B在抑制SCNT胚胎中的ICM增殖中发挥作用,可能通过p21.
- 针对H3K4me3脱甲基化和调节BCL11B表达等表观遗传修饰可能会提高牛中的SCNT效率.
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