Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
FEBS Lett. 2012 Jul 4;586(14):1953-8. doi: 10.1016/j.febslet.2012.03.023. Epub 2012 Apr 10.
The canonical TGF-β/Smad signaling pathway was delineated in the mid 90s and enriched over the past decade with many findings about its specificity, regulation, networking, and malfunctions in disease. However, a growing understanding of the chromatin status of a critical class of TGF-β target genes - the genes controlling differentiation of embryonic stem cells - recently prompted a reexamination of this pathway and its critical role in the regulation of stem cell differentiation. The new findings reveal master regulators of the pluripotent state set the stage for Smad-mediated activation of master regulators of the next differentiation stage. Furthermore, a novel branch of the TGF-β/Smad pathway has been identified in which a chromatin-reading Smad complex makes the master differentiation genes accessible to canonical Smad complexes for transcriptional activation. These findings provide exciting new insights into the global role of TGF-β signaling in the regulators of stem cell fate.
经典的 TGF-β/Smad 信号通路在 90 年代中期被描绘出来，并在过去十年中通过许多关于其特异性、调节、网络以及在疾病中的功能障碍的发现而得到丰富。然而，人们对一类关键的 TGF-β 靶基因——控制胚胎干细胞分化的基因——的染色质状态的理解不断加深，最近促使人们重新审视这一通路及其在干细胞分化调控中的关键作用。新的发现揭示了多能状态的主调控因子为 Smad 介导的下一个分化阶段的主调控因子的激活奠定了基础。此外，已经确定了 TGF-β/Smad 通路的一个新分支，其中一个染色质阅读 Smad 复合物使主分化基因可被经典 Smad 复合物用于转录激活。这些发现为 TGF-β 信号在干细胞命运调控中的全局作用提供了令人兴奋的新见解。
