Wellcome Trust Centre for Stem Cell Research, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QR, UK.
Adv Exp Med Biol. 2013;786:307-28. doi: 10.1007/978-94-007-6621-1_17.
The specialized cell types of tissues and organs are generated during development and are replenished over lifetime though the process of differentiation. During differentiation the characteristics and identity of cells are changed to meet their functional requirements. Differentiated cells then faithfully maintain their characteristic gene expression patterns. On the molecular level transcription factors have a key role in instructing specific gene expression programs. They act together with chromatin regulators which stabilize expression patterns. Current evidence indicates that epigenetic mechanisms are essential for maintaining stable cell identities. Conversely, the disruption of chromatin regulators is associated with disease and cellular transformation. In mammals, a large number of chromatin regulators have been identified. The Polycomb group complexes and the DNA methylation system have been widely studied in development. Other chromatin regulators remain to be explored. This chapter focuses on recent advances in understanding epigenetic regulation in embryonic and adult stem cells in mammals. The available data illustrate that several chromatin regulators control key lineage specific genes. Different epigenetic systems potentially could provide stability and guard against loss or mutation of individual components. Recent experiments also suggest intervals in cell differentiation and development when new epigenetic patterns are established. Epigenetic patterns have been observed to change at a progenitor state after stem cells commit to differentiation. This finding is consistent with a role of epigenetic regulation in stabilizing expression patterns after their establishment by transcription factors. However, the available data also suggest that additional, presently unidentified, chromatin regulatory mechanisms exist. Identification of these mechanism is an important aim for future research to obtain a more complete framework for understanding stem cell differentiation during tissue homeostasis.
组织和器官的特化细胞类型是在发育过程中产生的，并通过分化过程在一生中得到补充。在分化过程中，细胞的特征和身份发生变化，以满足其功能需求。分化后的细胞然后忠实地维持其特征基因表达模式。在分子水平上，转录因子在指导特定基因表达程序方面起着关键作用。它们与稳定表达模式的染色质调节剂一起发挥作用。目前的证据表明，表观遗传机制对于维持稳定的细胞身份是必不可少的。相反，染色质调节剂的破坏与疾病和细胞转化有关。在哺乳动物中，已经鉴定出大量的染色质调节剂。Polycomb 复合物和 DNA 甲基化系统在发育过程中得到了广泛的研究。其他染色质调节剂仍有待探索。本章重点介绍了近年来在理解哺乳动物胚胎和成体干细胞中表观遗传调控方面的进展。现有数据表明，几个染色质调节剂控制着关键的谱系特异性基因。不同的表观遗传系统可能为单个成分的丢失或突变提供稳定性和保护。最近的实验还表明，在细胞分化和发育的不同阶段，新的表观遗传模式被建立。在干细胞分化为祖细胞后，观察到表观遗传模式发生变化。这一发现与转录因子建立表达模式后，表观遗传调控在稳定表达模式中的作用一致。然而，现有数据还表明，存在其他目前尚未识别的染色质调节机制。鉴定这些机制是未来研究的一个重要目标，以获得更完整的框架来理解组织稳态中的干细胞分化。
