Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Cell Res. 2012 Jan;22(1):142-54. doi: 10.1038/cr.2011.171. Epub 2011 Nov 8.
Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing, disease modeling and cell-based therapy. However, without procardiogenic growth factors, the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous. Here, we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs), and consistent with other reports of iPSCs derived from various somatic cell types, VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, the majority of ViPSC-derived cardiomyocytes display a ventricular phenotype. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells.
多能干细胞衍生的心肌细胞可应用于药物测试、疾病建模和基于细胞的治疗。然而，如果没有促心肌生成的生长因子，多能干细胞向心肌细胞的生成效率通常较低，且产生的心肌细胞群体具有异质性。在这里，我们证明了诱导多能干细胞（iPSCs）可从鼠心室肌细胞（VMs）中获得，与其他各种体细胞类型来源的 iPSCs 的报告一致，VM 来源的 iPSCs（ViPSCs）与遗传匹配的胚胎干细胞（ESCs）或尾尖成纤维细胞来源的 iPSCs 相比，自发分化为搏动性心肌细胞的倾向明显更高。引人注目的是，大多数 ViPSC 衍生的心肌细胞表现出心室表型。ViPSCs 中增强的心室肌生成是通过分化早期心血管祖细胞数量的增加来介导的。为了研究 ViPSCs 中增强的心室肌生成的机制，我们进行了全基因组表达和 DNA 甲基化分析，揭示了一种独特的表观遗传特征，可能参与了多能干细胞中 VM 命运的指定。
