Mechanisms controlling embryonic stem cell self-renewal and differentiation.
Mechanisms controlling embryonic stem cell self-renewal and differentiation.
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DOI：
10.1615/critreveukargeneexpr.v16.i3.20
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发表时间：
2006
影响因子：
1.6
通讯作者：
Yu Sun;Huai Li;Henry Yang;M. Rao;Ming Zhan
中科院分区：
文献类型：
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作者：
Yu Sun;Huai Li;Henry Yang;M. Rao;Ming Zhan
胚胎干（ES）细胞是多能细胞，具有无限复制潜力和分化成所有类型细胞的能力。了解 ES 细胞多能性的调节机制对于实现其在再生医学和科学领域的潜力至关重要。 ES 细胞的跨物种研究已经确定了自我更新和分化的基础途径和网络，或者是物种特异性的途径和网络。尽管多能性作为多细胞生物体的基本功能在进化中得到保留，但分化的机制在很大程度上导致了来自不同组织或物种的干细胞之间的差异。转录组作图分析确定了 ES 状态特有的基因共表达模式的染色体结构域，并证明 ES 细胞发育的调节在局部染色体结构域水平和全局水平上都有效。来自多个途径的组合信号调节对 ES 细胞命运决定至关重要的关键内在因子的表达。特别是由 Oct4、Sox2 和 Nanog 形成的调控核心，激活对自我更新至关重要的基因并抑制启动分化的基因，从而控制 ES 细胞的多能性。在这里，我们回顾了有关控制 ES 细胞发育的机制的最新发现。通过整合不同来源的数据，我们展示了 ES 细胞如何做出自我更新或分化决定的全局图景。
Embryonic stem (ES) cells are pluripotent cells with indefinite replication potential and ability to differentiate into all types of cells. An understanding of the regulatory mechanisms responsible for pluripotency in ES cells is critical for realizing their potential in regenerative medicine and science. Cross-species studies on ES cells have identified pathways and networks that are either fundamental to or species-specific for self-renewal and differentiation. Although pluripotency as an essential function in multicellular organisms is conserved through evolution, mechanisms primed for differentiation contribute substantially to the differences among stem cells derived from different tissues or species. Transcriptome mapping analysis has determined the chromosomal domains of gene coexpression patterns specific to the ES state and demonstrated that regulation of ES cell development is operative at both the local chromosomal domain level and global level. Combinatorial signals from multiple pathways regulate the expression of key intrinsic factors critical for ES cell fate determination. The regulatory core formed by Oct4, Sox2, and Nanog, in particular, activates genes critical for self-renewal and represses genes initiating differentiation, controlling ES cell pluripotency. Here, we review recent findings on mechanisms controlling ES cell development. By integrating data from different sources, we present a global picture of how ES cells reach the decision of self-renewal or differentiation.