Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA.
Stem Cell Rev Rep. 2011 Nov;7(4):836-46. doi: 10.1007/s12015-011-9275-1.
Embryonic stem cells and induced pluripotent stem (iPS) cells are characterized by their ability to self-renew and to generate differentiated cells of all three germ layers. This potential makes them an attractive source to address question of developmental and also for use in clinical regenerative medicine. Although the culture conditions to maintain pluripotency and reprogramming technologies have been established, the underlying molecular mechanisms are incompletely understood. Accumulating evidence indicates that the Wnt/β-catenin signaling pathway plays a pivotal role in the maintenance of pluripotency as well as in the process of somatic cell reprogramming. Reciprocally, Wnt/β-catenin signaling also plays a critical role in the lineage decision/commitment process. These dramatically different outcomes upon activation of the Wnt signaling cascade has fueled enormous controversy concerning the role of Wnt signaling in the maintenance of potency and induction of differentiation in stem cells. Here, we discuss and explore the divergent roles of the Wnt signaling pathways based on findings from our lab. Accumulated results from our lab indicate the usage of a critical switching mechanism that regulates the divergent Wnt/catenin transcriptional programs associated with either maintenance of potency or initiation of differentiation.
胚胎干细胞和诱导多能干细胞（iPS 细胞）的特征是它们具有自我更新和产生所有三个胚层分化细胞的能力。这种潜能使它们成为研究发育问题的有吸引力的来源，也可用于临床再生医学。尽管已经建立了维持多能性和重编程技术的培养条件，但潜在的分子机制尚不完全清楚。越来越多的证据表明，Wnt/β-连环蛋白信号通路在维持多能性以及体细胞重编程过程中起着关键作用。反过来，Wnt/β-连环蛋白信号通路在谱系决定/承诺过程中也起着关键作用。Wnt 信号级联的激活产生了截然不同的结果，这引发了关于 Wnt 信号在维持干细胞的潜能和诱导分化中的作用的巨大争议。在这里，我们根据我们实验室的发现讨论和探讨了 Wnt 信号通路的不同作用。我们实验室的累积结果表明，存在一种关键的转换机制，调节与维持潜能或启动分化相关的不同 Wnt/β-连环蛋白转录程序。
