在心脏成熟过程中,ARID1A介导的YAP抑制抑制了心肌细胞增殖
Cornelis J Boogerd1, Ilaria Perini2, Eirini Kyriakopoulou2
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, Netherlands. K.boogerd@hubrecht.eu.
Nature communications
|August 5, 2023
概括
成年心肌细胞由于缺乏增殖不能再生. Arid1a是一种染色质重塑剂,抑制了增殖,促进了成熟,为心脏修复研究提供了新的途径.
科学领域:
- 心脏病学 心脏病学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 成年心肌细胞的增殖是有限的,阻碍了受伤后的心脏再生.
- 了解转换到非再生状态对于开发治疗策略至关重要.
研究的目的:
- 研究Arid1a在调节产后心肌细胞增殖和成熟中的作用.
- 阐明Arid1a控制心肌细胞循环的分子机制.
主要方法:
- 进行了全基因组转录组和表观基因组分析.
- 评估了Arid1a与YAP/TAZ和TEAD的相互作用.
- 在缺血性心脏病的小鼠模型中评估了Arid1a的作用.
主要成果:
- 一个SWI/SNF复合体子单元Arid1a抑制心肌细胞的增殖,促进心肌细胞的成熟.
- 阿里德1a促进转录因子的DNA访问,驱动心肌细胞成熟.
- Arid1a直接抑制了YAP/TAZ,将它们从TEAD中隔离出来.
- 经过缺血病损伤的Arid1a的失活会增加边境区域心肌细胞的增殖.
结论:
- 阿里德1a是心肌细胞成熟的关键调节剂,也是增殖的关键抑制剂.
- 准Arid1a可能为促进心脏再生提供一种新的策略.
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