Birket Matthew J, Mummery Christine L
Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Dev Biol. 2015 Apr 15;400(2):169-79. doi: 10.1016/j.ydbio.2015.01.012. Epub 2015 Jan 24.
Human pluripotent stem cells can now be routinely differentiated into cardiac cell types including contractile cardiomyocytes, enabling the study of heart development and disease in vitro, and creating opportunities for the development of novel therapeutic interventions for patients. Our grasp of the system, however, remains partial, and a significant reason for this has been our inability to effectively purify and expand the intermediate cardiovascular progenitor cells (CPCs) equivalent to those studied in heart development. Doing so could facilitate the construction of a cardiac lineage cell fate map, boosting our capacity to more finely control stem cell lineage commitment to functionally distinct cardiac identities, as well as providing a model for identifying which genes confer cardiac potential on CPCs. This review offers a perspective on CPC development as understood from model organisms and pluripotent stem cell systems, focusing on issues of identity as well as the signalling implicated in inducing, expanding and patterning these cells.
人类多能干细胞现在可以常规地分化为包括收缩性心肌细胞在内的心脏细胞类型,从而能够在体外研究心脏发育和疾病,并为开发针对患者的新型治疗干预措施创造机会。然而,我们对该系统的理解仍然不全面,一个重要原因是我们无法有效地纯化和扩增与心脏发育中所研究的细胞相当的中间心血管祖细胞(CPCs)。这样做有助于构建心脏谱系细胞命运图谱,提高我们更精确地控制干细胞谱系定向分化为功能不同的心脏细胞类型的能力,同时还能提供一个模型来确定哪些基因赋予CPCs心脏潜能。本文综述从模式生物和多能干细胞系统的角度对CPCs的发育进行了阐述,重点关注细胞身份问题以及与诱导、扩增和调控这些细胞相关的信号传导。