Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, Université de Strasbourg, Illkirch Cedex, France.
Curr Opin Endocrinol Diabetes Obes. 2010 Dec;17(6):500-6. doi: 10.1097/MED.0b013e3283405325.
Pluripotency is the ability of a cell to give rise to all the tissues of the adult body. During development, both genetic and epigenetic mechanisms are proposed to be involved in the establishment of the pluripotent state in the cells of the epiblast. Here, we review recent findings on the biological function and epigenetic regulation of reprogramming factors with a particular focus on the early mouse embryo.
A number of functional studies have identified a group of transcription factors required for reprogramming during mouse preimplantation development. Among these transcription factors, Oct4, Sox2, and Nanog are also crucial for establishment and/or maintenance of pluripotency in vivo. Genome-wide studies with ES cells have highlighted the colocalization of these factors onto ES cell chromatin and the existence of a transcriptional network that might direct pluripotency. Furthermore, recent studies on transcription factor-mediated induced reprogramming to induced pluripotent stem cells have revealed roles of these transcription factors on reprogramming.
Oct4, Sox2, and Nanog seem to work at different times of the reprogramming process in vivo. Elucidating the regulatory mechanisms of these factors provides not only insights into the reprogramming mechanisms but also in the regulation of mouse preimplantation development.
多能性是指细胞产生成体组织的能力。在发育过程中,遗传和表观遗传机制被提出参与了上胚层细胞中多能状态的建立。在这里,我们回顾了关于重编程因子的生物学功能和表观遗传调控的最新发现,特别关注早期小鼠胚胎。
许多功能研究已经确定了一组在小鼠胚胎植入前发育过程中进行重编程所需的转录因子。在这些转录因子中,Oct4、Sox2 和 Nanog 对于体内多能性的建立和/或维持也是至关重要的。与胚胎干细胞的全基因组研究强调了这些因子在胚胎干细胞染色质上的共定位以及可能指导多能性的转录网络的存在。此外,最近关于转录因子介导的诱导重编程为诱导多能干细胞的研究揭示了这些转录因子在重编程中的作用。
Oct4、Sox2 和 Nanog 似乎在体内重编程过程的不同时间发挥作用。阐明这些因子的调控机制不仅提供了对重编程机制的深入了解,也提供了对小鼠胚胎植入前发育调控的了解。