美国斯坦福大学心血管病研究所Mingxia Gu研究组取得最新进展。他们发现内在性心内膜缺陷导致增生性左心综合征（HLHS）。最新成果发表在2020年出8月17日出版的《细胞-干细胞》杂志上。

他们通过hiPSC来源的心内膜和人胎儿心脏组织的单细胞RNA谱来研究左心室发育不全，从而了发现HLHS的心内膜发育受损。内在性心内膜缺陷导致异常的内皮向间充质转变，NOTCH信号和细胞外基质组织，这是导致瓣膜形成的关键因素。心内膜异常会通过破坏纤连蛋白-整合素信号传导，而导致心肌细胞增殖和成熟减少，这与最近描述的与异常心内膜基因和纤连蛋白调节相关的从头HLHS突变相吻合。这些结果共同揭示了心内膜在HLHS病因学中的关键作用，并为心内膜功能再生策略提供了原理。

据悉，发育不良的HLHS是一种复杂的先天性心脏病，其特征在于左心室、相关瓣膜和升主动脉异常。研究已经显示出内在的心肌缺陷，但不足以解释心内膜来源的心脏瓣膜、隔膜和脉管系统的发育缺陷。

附：英文原文

Title: Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome

Author: Yifei Miao, Lei Tian, Marcy Martin, Sharon L. Paige, Francisco X. Galdos, Jibiao Li, Alyssa Klein, Hao Zhang, Ning Ma, Yuning Wei, Maria Stewart, Soah Lee, Jan-Renier Moonen, Bing Zhang, Paul Grossfeld, Seema Mital, David Chitayat, Joseph C. Wu, Marlene Rabinovitch, Timothy J. Nelson, Shuyi Nie, Sean M. Wu, Mingxia Gu

Issue&Volume: 2020-08-17

Abstract: Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterizedby abnormalities in the left ventricle, associated valves, and ascending aorta. Studieshave shown intrinsic myocardial defects but do not sufficiently explain developmentaldefects in the endocardial-derived cardiac valve, septum, and vasculature. Here, weidentify a developmentally impaired endocardial population in HLHS through single-cellRNA profiling of hiPSC-derived endocardium and human fetal heart tissue with an underdevelopedleft ventricle. Intrinsic endocardial defects contribute to abnormal endothelial-to-mesenchymaltransition, NOTCH signaling, and extracellular matrix organization, key factors invalve formation. Endocardial abnormalities cause reduced cardiomyocyte proliferationand maturation by disrupting fibronectin-integrin signaling, consistent with recentlydescribed de novo HLHS mutations associated with abnormal endocardial gene and fibronectin regulation.Together, these results reveal a critical role for endocardium in HLHS etiology andprovide a rationale for considering endocardial function in regenerative strategies.

DOI: 10.1016/j.stem.2020.07.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30353-2