Embryonic stem cell differentiation: A chromatin perspective-猫眼课题宝

胚胎干细胞分化：染色质视角

DOI：

发表时间：

2003

期刊：

Reproductive Biology and Endocrinology

影响因子：

4.4

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

T. Rasmussen

胚胎干（ES）细胞在治疗人类退行性疾病方面具有巨大的前景。由于 ES 细胞具有多能性，因此它们可以定向分化为许多具有潜在治疗价值的替代细胞类型。这种“合理定向 ES 细胞分化”的尝试构成了概括体外正常发育各方面的尝试。所有分化的细胞都保留相同的 DNA 含量，但基因表达因细胞类型而异。因此，一个有效的表观遗传系统已经进化来协调和维持基因表达的组织特异性模式。最近的进展表明，控制基因表达的表观遗传调控的机制植根于染色质动力学的细节。当胚胎细胞分化时，某些基因被激活，而另一些基因则被沉默。这些激活和沉默事件与细胞谱系的分配完美协调。发育调控基因染色质的重塑与谱系定型同时发生。卵母细胞、早期胚胎和胚胎干细胞含有有效的染色质重塑活性，这一观察结果表明染色质动态对于早期谱系决策可能特别重要。染色质动力学也参与成体干细胞的分化，其中专门染色质在组织特异性基因上的组装已被详细研究。未来几年，从染色质动力学的角度理解干细胞分化和发育生物学可能会取得显着进展。

Embryonic stem (ES) cells hold immense promise for the treatment of human degenerative disease. Because ES cells are pluripotent, they can be directed to differentiate into a number of alternative cell-types with potential therapeutic value. Such attempts at "rationally-directed ES cell differentiation" constitute attempts to recapitulate aspects of normal development in vitro. All differentiated cells retain identical DNA content, yet gene expression varies widely from cell-type to cell-type. Therefore, a potent epigenetic system has evolved to coordinate and maintain tissue-specific patterns of gene expression. Recent advances show that mechanisms that govern epigenetic regulation of gene expression are rooted in the details of chromatin dynamics. As embryonic cells differentiate, certain genes are activated while others are silenced. These activation and silencing events are exquisitely coordinated with the allocation of cell lineages. Remodeling of the chromatin of developmentally-regulated genes occurs in conjunction with lineage commitment. Oocytes, early embryos, and ES cells contain potent chromatin-remodeling activities, an observation that suggests that chromatin dynamics may be especially important for early lineage decisions. Chromatin dynamics are also involved in the differentiation of adult stem cells, where the assembly of specialized chromatin upon tissue-specific genes has been studied in fine detail. The next few years will likely yield striking advances in the understanding of stem cell differentiation and developmental biology from the perspective of chromatin dynamics.