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利用实验鼠胚胎培育出纯粹的心肌细胞

2009年05月06日 浏览量: 评论(0) 来源:新华网 作者:佚名 责任编辑:lwc
摘要:日本东京工业大学研究人员在新一期英国《自然》杂志上发表论文说,他们通过向实验鼠的受精卵导入3个基因,成功令其胚胎的中胚层分化成纯粹的心肌细胞。

日本东京工业大学研究人员在新一期英国《自然》杂志上发表论文说,他们通过向实验鼠的受精卵导入3个基因,成功令其胚胎的中胚层分化成纯粹的心肌细胞。

获得这项成果的是东京工业大学的竹内纯等研究人员。他们将“Gata4”、“Tbx5”和“Baf60C”3个基因导入受精第六天的实验鼠受精卵中,结果受精卵逐渐变成胚胎后,本该分化成手脚肌肉和胎儿羊膜的中胚层细胞分化生成了心肌细胞。

向胚胎干细胞或诱导多功能干细胞添加生理活性物质等也能培养出心肌细胞。但是,用这类方法培育出的心肌细胞往往混在多种细胞之中,而这次研究人员培育出的心肌细胞完全没有混杂别的细胞。这项成果将有助于推动心脏再生医疗研究以及解开心脏发育的机制。

推荐原始出处:

Nature 26 April 2009 | doi:10.1038/nature08039

Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors

Jun K. Takeuchi1,2 & Benoit G. Bruneau1,3

1 Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA
2 Division of Cardiovascular Research, Global-Edge Institute, Tokyo Institute of Technology, Frontier S2-16, Nagatsuda, Midori-ku, Yokohama, Kanagawa 226-8503, Japan
3 Department of Pediatrics, Cardiovascular Research Institute, and Institute for Regeneration Medicine, University of California, San Francisco, California 94158, USA

Heart disease is the leading cause of mortality and morbidity in the western world. The heart has little regenerative capacity after damage, leading to much interest in understanding the factors required to produce new cardiac myocytes. Despite a robust understanding of the molecular networks regulating cardiac differentiation1, 2, no single transcription factor or combination of factors has been shown to activate the cardiac gene program de novo in mammalian cells or tissues. Here we define the minimal requirements for transdifferentiation of mouse mesoderm to cardiac myocytes. We show that two cardiac transcription factors, Gata4 and Tbx5, and a cardiac-specific subunit of BAF chromatin-remodelling complexes, Baf60c (also called Smarcd3), can direct ectopic differentiation of mouse mesoderm into beating cardiomyocytes, including the normally non-cardiogenic posterior mesoderm and the extraembryonic mesoderm of the amnion. Gata4 with Baf60c initiated ectopic cardiac gene expression. Addition of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of non-cardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac genes, indicating a novel instructive role for BAF complexes in tissue-specific regulation. The combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes.

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