2012年9月14日 訊 /生物谷BIOON/ --9月13日,，國際著名雜志Cell在線發(fā)表了華盛頓大學(xué)干細(xì)胞和再生醫(yī)學(xué)研究所Charles E. Murry和醫(yī)學(xué)系Stamatoyannopoulos等的一篇題為A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development “人胚胎干細(xì)胞中瞬時染色體標(biāo)志用于鑒定心臟發(fā)育中的調(diào)節(jié)子”的科研論文,，首次提出瞬時特定的染色體結(jié)構(gòu)可以作為一種標(biāo)志，用于鑒定干細(xì)胞分化中的調(diào)節(jié)子,。
人胚胎干細(xì)胞（embryonic stem cells ,，ESCs）定向分化成心血管細(xì)胞的過程可以用于研究人的心臟發(fā)育,。胚胎干細(xì)胞分化過程中,，染色體重塑模式在祖細(xì)胞和分化細(xì)胞中有顯著差異,，但有關(guān)分化中染色體變化的瞬時動力學(xué)還不是很清楚。
此項(xiàng)研究結(jié)果表明,，人胚胎干細(xì)胞分化成心血管細(xì)胞的過程中伴隨著染色體結(jié)構(gòu)程序性的瞬間變化,。這一瞬時染色體結(jié)構(gòu)具有獨(dú)特性，可以用于鑒定心臟發(fā)育中的調(diào)節(jié)子,。
利用模式動物斑馬魚,，研究人員依據(jù)分化過程中染色體的特定結(jié)構(gòu)，鑒定出心臟發(fā)育中重要的調(diào)節(jié)子——同源框基因MEIS2,。結(jié)果表明MEIS2對心管以及隨后的心襻的形成至關(guān)重要,。
本研究的亮點(diǎn)在于發(fā)現(xiàn)人胚胎干細(xì)胞分化過程中染色體結(jié)構(gòu)變化可以作為鑒定心臟發(fā)育中的調(diào)節(jié)子的標(biāo)志，這一發(fā)現(xiàn)可廣泛用于其它模式生物中鑒定干細(xì)胞分化中的調(diào)節(jié)子,。(生物谷Bioon.com)
doi:10.1016/j.cell.2012.08.027
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A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development
Sharon L. Paige,，Sean Thomas，Cristi L. Stoick-Cooper,，Hao Wang,，Lisa Maves， Richard Sandstrom,，Lil Pabon,，Hans Reinecke，Gabriel Pratt,，Gordon Keller,，Randall T. Moon，John Stamatoyannopoulos,，Charles E. MurrySee Affiliations
Directed differentiation of human embryonic stem cells (ESCs) into cardiovascular cells provides a model for studying molecular mechanisms of human cardiovascular development. Although it is known that chromatin modification patterns in ESCs differ markedly from those in lineage-committed progenitors and differentiated cells,， the temporal dynamics of chromatin alterations during differentiation along a defined lineage have not been studied. We show that differentiation of human ESCs into cardiovascular cells is accompanied by programmed temporal alterations in chromatin structure that distinguish key regulators of cardiovascular development from other genes. We used this temporal chromatin signature to identify regulators of cardiac development， including the homeobox gene MEIS2. Using the zebrafish model,， we demonstrate that MEIS2 is critical for proper heart tube formation and subsequent cardiac looping. Temporal chromatin signatures should be broadly applicable to other models of stem cell differentiation to identify regulators and provide key insights into major developmental decisions.
