心臟受損后幾乎沒有再生能力,，所以了解產(chǎn)生新的心肌細胞所需因素是人們非常感興趣的問題,。
Jun Takeuchi 和Benoit Bruneau對小鼠中胚層向心肌細胞的分化轉(zhuǎn)移進行了研究，發(fā)現(xiàn)兩個心肌轉(zhuǎn)錄因子和BAF染色質(zhì)重塑復(fù)合物的一個心肌特異性亞單元足以引導(dǎo)小鼠中胚層向擴張的心肌細胞的轉(zhuǎn)化,。再增添一個轉(zhuǎn)錄因子,，會促進向收縮的心肌細胞的轉(zhuǎn)化，促進對非心肌中胚層基因的抑制,。確定心肌細胞分化的要求,，從長遠來講可幫助實現(xiàn)再生用于治療的心肌細胞的目標(biāo)。(生物谷Bioon.com)
生物谷推薦原始出處：
Nature 459, 708-711 (4 June 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.
