组蛋白伴侣 CAF-1 在细胞可塑性中的新兴作用。
Emerging roles of the histone chaperone CAF-1 in cellular plasticity.
机构信息
Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
Department of Molecular Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Center for Regenerative Medicine, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Cancer Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA.
出版信息
Curr Opin Genet Dev. 2017 Oct;46:83-94. doi: 10.1016/j.gde.2017.06.004. Epub 2017 Jul 7.
During embryonic development, cells become progressively restricted in their differentiation potential. This is thought to be regulated by dynamic changes in chromatin structure and associated modifications, which act together to stabilize distinct specialized cell lineages. Remarkably, differentiated cells can be experimentally reprogrammed to a stem cell-like state or to alternative lineages. Thus, cellular reprogramming provides a valuable platform to study the mechanisms that normally safeguard cell identity and uncover factors whose manipulation facilitates cell fate transitions. Recent work has identified the chromatin assembly factor complex CAF-1 as a potent barrier to cellular reprogramming. In addition, CAF-1 has been implicated in the reversion of pluripotent cells to a totipotent-like state and in various lineage conversion paradigms, suggesting that modulation of CAF-1 levels may endow cells with a developmentally more plastic state. Here, we review these exciting results, discuss potential mechanisms and speculate on the possibility of exploiting chromatin assembly pathways to manipulate cell identity.
在胚胎发育过程中，细胞的分化潜能逐渐受到限制。这被认为是由染色质结构和相关修饰的动态变化所调控的，这些变化共同作用，稳定不同的特化细胞谱系。值得注意的是，分化细胞可以通过实验被重新编程为类似于干细胞的状态或其他谱系。因此，细胞重编程为研究通常保护细胞身份的机制以及发现操纵哪些因素有助于细胞命运转变提供了有价值的平台。最近的工作已经确定了染色质组装因子复合物 CAF-1 是细胞重编程的一个强大障碍。此外，CAF-1 已被牵连到多能性细胞向全能性样状态的逆转以及各种谱系转换范例中，这表明 CAF-1 水平的调节可能使细胞具有更具发育可塑性的状态。在这里，我们回顾这些令人兴奋的结果，讨论潜在的机制，并推测利用染色质组装途径来操纵细胞身份的可能性。
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