Induction of cardiomyogenesis in human embryonic stem cells by human embryonic stem cell-derived definitive endoderm.
Induction of cardiomyogenesis in human embryonic stem cells by human embryonic stem cell-derived definitive endoderm.
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人胚胎干细胞来源的定形内胚层诱导人胚胎干细胞的心肌发生。
DOI：
10.1089/scd.2011.0161
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发表时间：
2012
影响因子：
4
通讯作者：
Lough,John
中科院分区：
文献类型：
--
作者：
VanOrman,JordanR;Si-Tayeb,Karim;Duncan,StephenA;Lough,John
我们以前报道过鸡前外侧内胚层（AL内胚层）诱导小鼠胚状体心肌发生。然而，从原肠胚阶段胚胎显微解剖AL内胚层的要求排除了其用于鉴定新的心肌发生因子或扩大心肌细胞数量用于治疗实验。为了解决这个问题，我们已经解决了是否人定形内胚层（hDE）细胞，它可以有效地产生大量的人胚胎干细胞（hESC），可以模仿AL内胚层诱导心肌发生的能力。结果表明，两个hDE细胞和他们的条件培养基诱导心肌发生在多能hESCs中，如有节奏的跳动和标记基因表达的免疫组织化学/定量聚合酶链反应监测所示。当多能hESC被预诱导至中-内胚层状态时，hDE的心肌发生作用增强。因为这种方法是易处理的和可扩展的，它可以促进识别新的hDE分泌的因子，以包含在定义的心肌鸡尾酒。
We previously reported that chick anterolateral endoderm (AL endoderm) induces cardiomyogenesis in mouse embryoid bodies. However, the requirement to micro-dissect AL endoderm from gastrulation-stage embryos precludes its use to identify novel cardiomyogenic factors, or to scale up cardiomyocyte numbers for therapeutic experiments. To circumvent this problem we have addressed whether human definitive endoderm (hDE) cells, which can be efficiently generated in large numbers from human embryonic stem cells (hESCs), can mimic the ability of AL endoderm to induce cardiac myogenesis. Results demonstrate that both hDE cells and medium conditioned by them induce cardiac myogenesis in pluripotent hESCs, as indicated by rhythmic beating and immunohistochemical/quantitative polymerase chain reaction monitoring of marker gene expression. The cardiomyogenic effect of hDE is enhanced when pluripotent hESCs are preinduced to the mes-endoderm state. Because this approach is tractable and scalable, it may facilitate identification of novel hDE-secreted factors for inclusion in defined cardiomyogenic cocktails.