Notch Inhibition Promotes Human Embryonic Stem Cell-Derived Cardiac Mesoderm Differentiation
Notch Inhibition Promotes Human Embryonic Stem Cell-Derived Cardiac Mesoderm Differentiation
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DOI：
10.1634/stemcells.2007-1053
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Choi, Young Min
中科院分区：
文献类型：
--
作者：
Jang, Jiho;Ku, Seung Yup;Choi, Young Min
Notch信号在小鼠胚胎干细胞心脏分化中的作用已被充分证明。我们研究了Notch信号传导是否在人类胚胎干细胞（hESC）中发挥类似的作用。虽然，如前所述，通过单独添加γ-分泌酶抑制剂（GSI）阻断Notch信号传导未能影响hESC分化，但我们发现GSI加体积减少的培养基（GSI/RVCM）加速中胚层分化。GSI/RVCM条件同时抑制了对神经外胚层谱系的承诺。此外，持续抑制Notch信号传导进一步增强向心脏中胚层的分化。在RVCM中，通常从开始GSI治疗后12天开始观察到自发搏动活动。此外，hESC衍生的心肌细胞表达连接蛋白43，并具有自发的钙振荡和心肌细胞搏动耦合到新生大鼠心肌细胞共培养时。这些发现强烈表明Notch信号传导在体外诱导和特化hESC衍生的心脏中胚层中的独特作用。干细胞2008;26：2782-2790
The roles of Notch signaling in cardiac differentiation from murine embryonic stem cells have been well documented. We investigated whether Notch signaling plays a similar role in human embryonic stem cells (hESCs). Although, as previously reported, blocking Notch signaling via the addition of gamma-secretase inhibitor (GSI) alone failed to affect hESC differentiation, we found that GSI plus reduced-volume culture medium (GSI/RVCM) accelerated mesodermal differentiation. GSI/RVCM conditions simultaneously suppressed commitment toward neuroectodermal lineages. Furthermore, sustained inhibition of Notch signaling further enhanced differentiation into cardiac mesoderm. Spontaneous beating activity was typically observed from 12 days after initiation of GSI treatment in RVCM. Moreover, hESC-derived cardiomyocytes expressed connexin 43 and possessed spontaneous calcium oscillations and cardiomyocyte beats coupled to neonatal rat cardiomyocytes when cocultured. These findings strongly suggest a distinct role for Notch signaling in the induction and specification of hESC-derived cardiac mesoderm in vitro. STEM CELLS 2008;26:2782-2790