美國(guó)格拉德斯通心血管病研究所的科學(xué)家宣稱(chēng),，他們首次確定了對(duì)培養(yǎng)新生心臟細(xì)胞極為關(guān)鍵的遺傳因子,。相關(guān)研究論文發(fā)表在的《自然》雜志上,。
幾十年來(lái),，科學(xué)家們始終未能確定一種能將非肌細(xì)胞轉(zhuǎn)化為心臟肌肉細(xì)胞的因子,。由貝努瓦·布魯諾博士帶領(lǐng)的研究小組發(fā)現(xiàn),，一個(gè)由3種基因相互結(jié)合而成的結(jié)合體可起到這種作用,。這是在哺乳動(dòng)物細(xì)胞或組織中,，相互結(jié)合的基因首次被確定具有促進(jìn)心臟細(xì)胞分裂的功能。
在西方,，心臟病已成了導(dǎo)致死亡的一大殺手,，在了解如何培養(yǎng)新的細(xì)胞來(lái)修復(fù)受損心臟方面，這項(xiàng)研究將是一個(gè)具有重要意義的開(kāi)端,。
這3個(gè)因子中的兩個(gè)是一種被稱(chēng)為轉(zhuǎn)錄因子的遺傳物質(zhì),，它們能控制基因與DNA的結(jié)合并確定哪種基因的活性被激活。這兩種被稱(chēng)為GATA4和TBX5的轉(zhuǎn)錄因子,，在發(fā)生突變后會(huì)導(dǎo)致心臟病,，同時(shí)也會(huì)通過(guò)相互作用控制其他基因。
當(dāng)研究人員在小鼠的細(xì)胞中加入一種不同的結(jié)合體時(shí),，這兩種轉(zhuǎn)錄因子在促進(jìn)普通細(xì)胞轉(zhuǎn)化為心臟細(xì)胞的過(guò)程中發(fā)揮了重要的作用,。令人驚訝的是一種被稱(chēng)為BAF60c的心肌特異性蛋白，它能幫助GATA4和TBX5這樣的轉(zhuǎn)錄因子進(jìn)入被其改變的DNA區(qū)域,，起到某種開(kāi)關(guān)的作用,。
而這些發(fā)現(xiàn)促使布魯諾小組對(duì)BAF60c在心臟細(xì)胞分化中的作用進(jìn)行了新的探索。研究發(fā)現(xiàn),，另外的第3個(gè)因子能分化為小鼠的中胚層,，而中胚層具有被誘導(dǎo)成骨骼、血液,、肌肉,、心臟以及其他組織的潛力，也可被培養(yǎng)成能使心臟有節(jié)奏跳動(dòng)的心肌細(xì)胞,。
布魯諾說(shuō),，這些因子為控制細(xì)胞分化提供了一種強(qiáng)大的機(jī)制，這一發(fā)現(xiàn)也將有助于人們對(duì)心肌細(xì)胞進(jìn)行重新編程,，以最終用于臨床目的,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature，doi:10.1038/nature08039,，Jun K. Takeuchi,，Benoit G. Bruneau
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.
