Regulation of transcription and cell identity by FGF/ERK signaling dynamics in embryonic stem cells

来自祖细胞的特化细胞类型的分化是胚胎发育和维持成体循环组织的基础。细胞外信号因子通过细胞内信号转导系统调节转录，在调节细胞分化中发挥核心作用。这些信号系统如何将定量信息从质膜传递到转录机制仍然知之甚少。我们在胚胎干细胞（ESCs）中通过细胞外调节激酶（ERK）的成纤维细胞生长因子（FGF）信号传导的背景下解决了这个问题。FGF/ERK信号在体外ESC分化的早期阶段起着至关重要的作用，反映了该信号系统在早期哺乳动物胚胎发生中的功能。我们将利用ESC系统对成像方法的可及性来阐明转录和信号动力学在从FGF受体到靶基因转录的忠实信息传递中的作用。具体来说，我们将验证ERK的动态激活模式编码有关配体丰度的信息的假设，这些信息可以通过转录机制解码。通过探索FGF信号动态编码的概念，我们的研究将影响我们对从质膜到细胞核的定量信息传递的理解。

The differentiation of specialized cell types from progenitor cells underlies both embryonic development and the maintenance of adult cycling tissues. Extracellular signaling factors play central roles in regulating cell differentiation by modulating transcription via intracellular signal transduction systems. How these signaling systems transmit quantitative information from the plasma membrane to the transcriptional machinery is still poorly understood. We address this question in the context of fibroblast growth factor (FGF) signaling through extracellular regulated kinase (ERK) in embryonic stem cells (ESCs). FGF/ERK signaling plays crucial roles during the earliest steps of ESC differentiation in vitro, mirroring the functions of this signaling system during early mammalian embryogenesis. We will exploit the accessibility of the ESC system for imaging approaches to elucidate the roles of both transcriptional and signaling dynamics for the faithful information transmission from the FGF receptor to the transcription of target genes. Specifically, we will test the hypothesis that dynamic activation patterns of ERK encode information about ligand abundance that can be decoded by the transcriptional machinery. By exploring the concept of dynamic encoding of FGF signals, our studies will impact our understanding of quantitative information transmission from the plasma membrane to the nucleus in general.