Itoh Fumiko, Watabe Tetsuro, Miyazono Kohei
Laboratory of Cardiovascular Medicine, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
Laboratory of Oncology, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; PRESTO, Japan Science Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
Semin Cell Dev Biol. 2014 Aug;32:98-106. doi: 10.1016/j.semcdb.2014.05.017. Epub 2014 Jun 6.
Members of the transforming growth factor-β (TGF-β) family have been implicated in embryogenesis as well as in the determination of the cell fates of mouse and human embryonic stem (ES) cells, which are characterized by their self-renewal and pluripotency. The cellular responses to TGF-β family signals are divergent depending on the cellular context and local environment. TGF-β family signals play critical roles both in the maintenance of the pluripotent state of ES cells by inducing the expression of Nanog, Oct4, and Sox2, and in their differentiation into various cell types by regulating the expression of master regulatory genes. Moreover, multiple lines of evidence have suggested the importance of TGF-β family signals in establishing induced pluripotent stem (iPS) cells. Since ES and iPS cells have great potential for applications in regenerative medicine, it is critical to figure out the mechanisms underlying their self-renewal, pluripotency, and differentiation. Here, we discuss the roles of TGF-β family ligands and their downstream signaling molecules, Smad proteins, in the maintenance of the pluripotency and lineage specification of mouse and human ES and iPS cells.
转化生长因子-β（TGF-β）家族成员已被证明与胚胎发育以及小鼠和人类胚胎干细胞（ES细胞）的细胞命运决定有关，这些细胞以自我更新和多能性为特征。细胞对TGF-β家族信号的反应因细胞背景和局部环境而异。TGF-β家族信号在通过诱导Nanog、Oct4和Sox2的表达来维持ES细胞的多能状态以及通过调节主调控基因的表达使其分化为各种细胞类型方面都发挥着关键作用。此外，多条证据表明TGF-β家族信号在诱导多能干细胞（iPS细胞）的建立中具有重要性。由于ES细胞和iPS细胞在再生医学中具有巨大的应用潜力，因此弄清楚它们自我更新、多能性和分化的潜在机制至关重要。在此，我们讨论TGF-β家族配体及其下游信号分子Smad蛋白在维持小鼠和人类ES细胞及iPS细胞的多能性和谱系特化中的作用。
