Revolutionizing Drug Discovery with Stem Cell Technology
Revolutionizing Drug Discovery with Stem Cell Technology
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DOI：
10.1042/bst0381027
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发表时间：
2010-08-01
影响因子：
3.9
通讯作者：
Smith, Austin G.
中科院分区：
文献类型：
--
作者：
Wray, Jason;Kalkan, Tuzer;Smith, Austin G.
多能性被定义为单个细胞响应胚胎或细胞培养环境的信号而启动成熟生物体所有谱系的能力。多能细胞没有预定的程序；这是一张白纸。这是哺乳动物发育和胚胎干细胞生物学的基础。这种初始细胞状态的设计原则是什么？多能性是如何获得和维持的？抑制ERKs（细胞外信号调节激酶）的激活对于ES细胞的建立和维持至关重要。抑制GSK3（糖原合成酶激酶3）加强了这种作用。我们回顾了选择性激酶抑制剂对多能细胞的作用，并考虑了这些作用是如何介导的。我们认为胚胎干细胞代表一种基态，即没有表观遗传限制的基础增殖状态，对外部刺激的需求最小。这种状态的稳定性反映在MEK（丝裂原活化蛋白激酶/ERK激酶）和GSK3小分子抑制剂存在下培养的ES细胞群体的均匀性上。
Pluripotency is defined as the capacity of individual cells to initiate all lineages of the mature organism in response to signals from the embryo or cell culture environment. A pluripotent cell has no predetermined programme; it is a blank slate. This is the foundation of mammalian development and of ES (embryonic stem) cell biology. What are the design principles of this naive cell state? How is pluripotency acquired and maintained? Suppressing activation of ERKs (extracellular-signal-regulated kinases) is critical to establishing and sustaining ES cells. Inhibition of GSK3 (glycogen synthase kinase 3) reinforces this effect. We review the effect of selective kinase inhibitors on pluripotent cells and consider how these effects are mediated. We propose that ES cells represent a ground state, meaning a basal proliferative state that is free of epigenetic restriction and has minimal requirements for extrinsic stimuli. The stability of this state is reflected in the homogeneity of ES cell populations cultured in the presence of small-molecule inhibitors of MEK (mitogen-activated protein kinase/ERK kinase) and GSK3.