心脏发育、疾病与再生中的转录调控：重新审视胎儿基因假说。
Transcriptional regulation in heart development, disease and regeneration: reassessing the fetal gene hypothesis.
作者信息
Porrello Enzo R, Lee Chang Jie Mick, Foo Roger S Y, Elliott David A
机构信息
Murdoch Children's Research Institute, The Royal Children's Hospital, Melbourne, Victoria, Australia.
Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine, The Royal Children's Hospital, Melbourne, Victoria, Australia.
出版信息
Nat Rev Cardiol. 2025 Sep 5. doi: 10.1038/s41569-025-01205-3.
A central paradigm in cardiac biology is the reactivation of the fetal gene programme in the adult heart in response to stress. This so-called 'fetal gene hypothesis' was first proposed almost 40 years ago following the observation that certain fetal contractile protein isoforms were re-expressed in hypertrophied ventricles in the rodent heart in response to haemodynamic overload. Consequently, this concept was broadly adopted, and activation of the fetal gene programme became synonymous in the literature with the cardiac stress response. Transcriptomic and epigenomic profiling studies from the past 20 years have revealed the extent to which the diseased heart redeploys fetal gene programmes in response to stress. In this Review, we describe the historical origins of the fetal gene hypothesis and re-evaluate the general principles of fetal gene regulation in heart development, disease and regeneration.
心脏生物学的一个核心范式是成年心脏在应激反应下重新激活胎儿基因程序。这种所谓的“胎儿基因假说”最早是在近40年前提出的，当时观察到某些胎儿收缩蛋白异构体在啮齿动物心脏因血流动力学过载而肥厚的心室中重新表达。因此，这一概念被广泛采用，胎儿基因程序的激活在文献中已成为心脏应激反应的同义词。过去20年的转录组学和表观基因组学分析研究揭示了患病心脏在应激反应下重新部署胎儿基因程序的程度。在本综述中，我们描述了胎儿基因假说的历史起源，并重新评估了心脏发育、疾病和再生过程中胎儿基因调控的一般原则。
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