氨酸特异性脱甲基酶1对Cend1的表观遗传抑制对于小鼠心脏发育至关重要
Huahua Liu1,2, Rui Zhou3, Shanshan Li1
1Department of Cardiology, First Affiliated Hospital, Cardiometabolic Innovation Center of Ministry of Education, Xi'an Jiaotong University, Xi'an, China.
iScience
|January 16, 2024
概括
氨酸特异性去甲基酶1 (LSD1) 对心脏发育至关重要. 这项研究揭示了LSD1如何通过抑制心脏生长所必需的Cend1来表观遗传控制心肌细胞增殖.
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
- 心血管研究研究心血管研究
背景情况:
- 控制心脏发育的表观遗传机制尚未完全理解.
- 像LSD1一样的基因组脱甲基酶与发育过程有关.
研究的目的:
- 阐明LSD1在心肌细胞增殖和心脏发育中的作用.
- 在心脏发育中识别LSD1的下游目标.
主要方法:
- 在小鼠心肌细胞中LSD1的有条件淘汰.
- 在体内和体外RNA测序 (RNA-seq).
- 在初级心肌细胞和人类诱导的多能干细胞中进行染色体免疫沉和功能测定.
主要成果:
- 通过抑制心肌细胞增殖,在小鼠中LSD1缺失严重损害了心脏生长.
- 鉴定出Cend1是一种直接转录的标,被LSD1.1抑制.
- LSD1的损失导致Cend1促销器的H3K4me2增加,从而提高了其转录的调节.
- 在LSD1缺乏的细胞中,Cend1敲击挽救了增殖缺陷.
- 在Lsd1无胚胎中,Cend1的遗传删除挽救了胚胎死亡率.
结论:
- LSD1-Cend1轴代表了对心肌细胞增殖的关键表观遗传调节机制.
- 这一途径对于小鼠正常胚胎和新生儿心脏发育至关重要.
- LSD1在抑制CEND1的作用在人类心肌细胞中得到保留.
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