Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
Stem Cells Dev. 2012 Mar 1;21(4):554-61. doi: 10.1089/scd.2011.0110. Epub 2011 Jun 24.
Fibroblast growth factor (FGF) signaling is implicated in the control of pluripotency and lineage differentiation of both human and mouse embryonic stem cells (mESCs). FGF4 dependent stimulation of ERK1/2 signaling triggers transition of pluripotent ESCs from self-renewal and lineage commitment. In this study, Sprouty 1 (Spry1) expression was observed in undifferentiated mESCs, where it modulated ERK1/2 activity. Spry1 was confirmed as dispensable for the maintenance of self-renewal. However, suppression of Spry1 expression and subsequent activation of ERK1/2 signaling promoted neural differentiation and inhibited endothelial differentiation of mESCs. Moreover, evidence is presented which indicates that SHP2, a major determinant of balance between mESC self-renewal and differentiation, directly regulates Spry1 activity to modulate ERK1/2 signaling and lineage-specific differentiation in mESCs. Our results show that Spry1 has an essential role in the lineage specific differentiation of mESCs.
成纤维细胞生长因子 (FGF) 信号通路在调控人及鼠胚胎干细胞 (mESCs) 的多能性和谱系分化中发挥重要作用。FGF4 依赖性的 ERK1/2 信号通路的激活促使多能性的 ESCs 从自我更新和谱系决定中转变。在本研究中，Sprouty 1 (Spry1) 在未分化的 mESCs 中表达，调节 ERK1/2 的活性。Spry1 对于维持自我更新是可有可无的。然而，抑制 Spry1 的表达和随后 ERK1/2 信号通路的激活促进了 mESCs 的神经分化，抑制了内皮分化。此外，本研究还提供了证据表明，SHP2 是决定 mESC 自我更新和分化平衡的主要决定因素，它可以直接调控 Spry1 的活性，从而调节 mESCs 中的 ERK1/2 信号通路和谱系特异性分化。我们的结果表明 Spry1 在 mESCs 的谱系特异性分化中具有重要作用。
