控制肌纤维发育和成熟的对立基因调节程序在单核分辨率上被揭示出来
Matthieu Dos Santos1, Akansha M Shah1, Yichi Zhang1
1Department of Molecular Biology, the Hamon Center for Regenerative Science and Medicine, and Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.
Nature communications
|July 19, 2023
概括
研究人员使用多原子单核RNA-seq和ATAC-seq绘制了小鼠骨肌肉发育的地图. 他们确定了像Myogenin,Klf5,Ade4和Maf这样的关键转录因子,对于肌肉基因激活和成熟至关重要,将收缩与发育联系起来.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 骨肌纤维在发育和成熟过程中表现出不同的基因程序.
- 控制特定阶段肌纤维特性的基因调节网络尚未完全理解.
- 了解这些网络对于破译肌肉发育和对神经活动的反应至关重要.
研究的目的:
- 为了生成小鼠骨肌肉发育的多原子地图.
- 确定控制肌肉纤维发育和成熟的基因调节网络.
- 研究神经活动在这些过程中的作用.
主要方法:
- 组合的多原子单核RNA测序 (snRNA-seq) 和ATAC测序 (ATAC-seq).
- 在多个胚胎,胎儿和产后阶段对小鼠骨肌的分析.
- 确定关键的转录因子及其调节作用.
主要成果:
- 肌原蛋白,Klf5和Ade4形成一个复合体,激活肌肉基因表达在发育肌纤维.
- 转录因子Maf在成熟过程中作为成熟的快速肌肉基因程序激活的开关.
- 在缺乏电压关闭的L型Ca2+通道 (Cav1.1) 的小鼠中观察到受损的Maf表达和肌纤维成熟 (Cav1.1).
结论:
- 这项研究提供了一个关于骨肌肉发育的全面的转录图谱.
- 确定了控制肌纤维形成和成熟的关键转录因子及其网络.
- 揭示了肌纤维发育,成熟和肌肉收缩之间的遗传联系.
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