奥地利科学院分子生物技术研究所（IMBA）Sasha Mendjan研究组近日取得一项新成果。他们利用心脏类器官揭示了人类心脏发生的自组织原理。该研究于2021年5月20日发表于国际一流学术期刊《细胞》杂志上。
他们从人类多能干细胞建立了自组织心脏类器官，它们本质上可以指定、构图和变形成包含腔的腔状结构。心脏类器官复杂性可通过指示心肌细胞和内皮层分离的信号以及指导心外膜的扩散，向内迁移和分化来控制。他们发现腔的形态发生是由中胚层WNT BMP信号轴控制，并需要其靶标HAND1，这是一种与发育性心脏腔室缺陷相关的转录因子。冷冻损伤后，心脏类器官会引发细胞类型依赖的细胞外基质积聚，这是再生和心脏病的早期标志。因此，人类心脏类器官是机械解剖自组织、先天性心脏缺陷的强大平台，并为将来的转化研究奠定了基础。
据了解，能够形成类组织结构的类器官改变了人们对人类发育和疾病建模的能力。除了人的心脏外，所有主要器官都报告了特定于谱系的自组织类器官。
附：英文原文
Title: Cardioids reveal self-organizing principles of human cardiogenesis
Author: Pablo Hofbauer, Stefan M. Jahnel, Nora Papai, Magdalena Giesshammer, Alison Deyett, Clara Schmidt, Mirjam Penc, Katherina Tavernini, Nastasja Grdseloff, Christy Meledeth, Lavinia Ceci Ginistrelli, Claudia Ctortecka, ejla alic, Maria Novatchkova, Sasha Mendjan
Issue&Volume: 2021-05-20
Abstract: Organoids capable of forming tissue-like structures have transformed our ability tomodel human development and disease. With the notable exception of the human heart,lineage-specific self-organizing organoids have been reported for all major organs.Here, we established self-organizing cardioids from human pluripotent stem cells thatintrinsically specify, pattern, and morph into chamber-like structures containinga cavity. Cardioid complexity can be controlled by signaling that instructs the separationof cardiomyocyte and endothelial layers and by directing epicardial spreading, inwardmigration, and differentiation. We find that cavity morphogenesis is governed by amesodermal WNT-BMP signaling axis and requires its target HAND1, a transcription factorlinked to developmental heart chamber defects. Upon cryoinjury, cardioids initiateda cell-type-dependent accumulation of extracellular matrix, an early hallmark of bothregeneration and heart disease. Thus, human cardioids represent a powerful platformto mechanistically dissect self-organization, congenital heart defects and serve asa foundation for future translational research.
DOI: 10.1016/j.cell.2021.04.034
Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00537-7