Nakano A, Nakano H, Chien K R
Cardiovascular Research Center, Massachusetts General Hospital, Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02114-2790, USA.
Cold Spring Harb Symp Quant Biol. 2008;73:297-306. doi: 10.1101/sqb.2008.73.055. Epub 2009 Feb 9.
During the past several years, advances at the intersection of cardiovascular development and heart stem cell biology have begun to reshape our view of the fundamental logic that drives the formation of discrete tissue components in the mammalian heart. Although many of the critical genes that control cardiac myogenesis have been identified, our understanding of how a highly diverse and specialized subset of heart cell lineages arises from mesodermal precursors and is subsequently assembled into distinct muscle chambers, coronary arterial tree and large vessels, valvular tissue, and conduction system/pacemaker cells remains at a relatively primitive stage. Recent studies have uncovered a diverse group of closely related heart progenitors that are central in controlling and coordinating these complex steps of cardiogenesis. Understanding the pathways that control their formation, renewal, and subsequent conversion to specific differentiated progeny forms the underpinning for unraveling the pathways for congenital heart disease and has direct relevance to cardiovascular regenerative medicine. This current brief review highlights the discovery and delineation of the role of Islet-1 cardiovascular progenitors in the generation of diverse heart cell lineages and how the implications of these findings are revising our classification and thinking about congenital heart disease in general.
在过去几年中,心血管发育与心脏干细胞生物学交叉领域的进展已开始重塑我们对驱动哺乳动物心脏中离散组织成分形成的基本逻辑的看法。尽管已经鉴定出许多控制心肌生成的关键基因,但我们对于高度多样且特化的心脏细胞谱系如何从中胚层前体产生,随后组装成不同的肌肉腔室、冠状动脉树和大血管、瓣膜组织以及传导系统/起搏细胞的理解仍处于相对原始的阶段。最近的研究发现了一组多样的密切相关的心脏祖细胞,它们在控制和协调心脏发生的这些复杂步骤中起着核心作用。了解控制它们形成、更新以及随后转化为特定分化后代的途径,是阐明先天性心脏病发病途径的基础,并且与心血管再生医学直接相关。本简要综述重点介绍了胰岛-1心血管祖细胞在多种心脏细胞谱系生成中的作用的发现和描述,以及这些发现如何总体上修正我们对先天性心脏病的分类和认识。