Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Essays Biochem. 2010 Sep 20;48(1):245-62. doi: 10.1042/bse0480245.
ESCs (embryonic stem cells), derived from the blastocyst stage embryo, are characterized by an indefinite ability for self-renewal as well as pluripotency, enabling them to differentiate into all cell types of the three germ layers. In the undifferentiated state, ESCs display a global promiscuous transcriptional programme which is restricted gradually upon differentiation. Supporting transcriptional promiscuity, chromatin in pluripotent cells is more 'plastic' or 'open', with decondensed heterochromatin architecture, enrichment of active histone modifications, and a hyperdynamic association of chromatin proteins with chromatin. During ESC differentiation, nuclear architecture and chromatin undergo substantial changes. Heterochromatin foci appear smaller, more numerous and more condensed in the differentiated state, the nuclear lamina becomes more defined and chromatin protein dynamics becomes restricted. In the present chapter we discuss chromatin plasticity and epigenetics and the mechanisms that regulate the various chromatin states, which are currently a central theme in the studies of stem cell maintenance and differentiation, and which will no doubt assist in delineating the secrets of pluripotency and self-renewal.
胚胎干细胞(ESCs)来源于囊胚期胚胎,具有无限的自我更新能力和多能性,使其能够分化为三个胚层的所有细胞类型。在未分化状态下,ESCs 表现出一种广泛的混杂转录程序,这种程序在分化过程中逐渐受到限制。支持转录混杂性,多能细胞中的染色质更“可塑性”或“开放”,具有去凝聚的异染色质结构、丰富的活性组蛋白修饰以及染色质蛋白与染色质的超动态关联。在 ESC 分化过程中,核结构和染色质发生了很大的变化。在分化状态下,异染色质焦点变得更小、更多、更浓缩,核层变得更加明确,染色质蛋白动力学受到限制。在本章中,我们讨论了染色质的可塑性和表观遗传学以及调节各种染色质状态的机制,这些机制目前是干细胞维持和分化研究的一个核心主题,毫无疑问将有助于描绘多能性和自我更新的秘密。