2012年9月14日 讯 /生物谷BIOON/ --9月13日，国际著名杂志Cell在线发表了华盛顿大学干细胞和再生医学研究所Charles E. Murry和医学系Stamatoyannopoulos等的一篇题为A Temporal Chromatin Signature in Human Embryonic Stem Cells Identifies Regulators of Cardiac Development “人胚胎干细胞中瞬时染色体标志用于鉴定心脏发育中的调节子”的科研论文，首次提出瞬时特定的染色体结构可以作为一种标志，用于鉴定干细胞分化中的调节子。
人胚胎干细胞（embryonic stem cells ，ESCs）定向分化成心血管细胞的过程可以用于研究人的心脏发育。胚胎干细胞分化过程中，染色体重塑模式在祖细胞和分化细胞中有显著差异，但有关分化中染色体变化的瞬时动力学还不是很清楚。
此项研究结果表明，人胚胎干细胞分化成心血管细胞的过程中伴随着染色体结构程序性的瞬间变化。这一瞬时染色体结构具有独特性，可以用于鉴定心脏发育中的调节子。
利用模式动物斑马鱼，研究人员依据分化过程中染色体的特定结构，鉴定出心脏发育中重要的调节子——同源框基因MEIS2。结果表明MEIS2对心管以及随后的心襻的形成至关重要。
本研究的亮点在于发现人胚胎干细胞分化过程中染色体结构变化可以作为鉴定心脏发育中的调节子的标志，这一发现可广泛用于其它模式生物中鉴定干细胞分化中的调节子。(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.
