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通过MEF2C/p300介导的表观遗传重塑促进诱导心肌细胞的成熟

Hidenori Kojima¹, Taketaro Sadahiro², Naoto Muraoka¹

¹Department of Cardiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

Stem cell reports

|June 14, 2023

概括

通过MYOD事务激活域激活MEF2C显著增强诱导心肌细胞 (iCM) 的生成和成熟. 这种MEF2C/p300相互作用驱动表观遗传重塑,对功能性心脏细胞发育至关重要.

科学领域:

心血管生物学心血管生物学
干细胞生物学干细胞生物学
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:

将纤维细胞直接重新编程成诱导心肌细胞 (iCMs) 是一个有前途的再生策略.
MEF2C,GATA4和TBX5 (GT) 是这个过程的关键心脏转录因子.
生成功能性和成熟的iCM仍然是低效的,机制不太清楚.

研究的目的:

研究提高iCM产生的效率和成熟度的方法.
阐明iCM成熟中的分子机制,特别是MEF2C和表观遗传修饰的作用.

主要方法:

过度表达转录激活的MEF2C与GT.GT.一起与MYOD交易激活域融合.
评估iCM的生成效率,转录形状,结构完整性和功能击.
研究p300在MEF2C介导的重编程和染色质重塑中的作用.
分析MEF2C拼接异型对iCM生成的影响.

主要成果:

与原生MEF2C相比,激活的MEF2C增加了30倍的殴打iCM生成.
由此产生的iCMs表现出增强的转录,结构和功能成熟度.
激活的MEF2C招募了p300和其他心脏TFs,诱导了染色质重塑.
抑制p300影响了心脏基因表达,ICM成熟和跳动细胞数量.
MEF2C拼接异型没有改善功能性iCM生成.

结论:

对MEF2C的转录激活显著促进诱导心肌细胞的生成和成熟.
由MEF2C/p300介导的表观遗传重塑是促进ICM成熟的关键机制.
针对MEF2C激活和p300相互作用,有可能改善心脏细胞重编程疗法.

关键词:

在MEF2C中,MEF2C是通过心脏重编程进行心脏重编程.这是心肌细胞 (cardiomyocyte).表观遗传学是指表观遗传学.成熟成熟成熟成熟.在P300上,P300是P300.

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