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

胚胎干细胞中 FGF/ERK 信号动力学对转录和细胞身份的调节

• 批准号: 441798639
• 负责人: Dr. Christian Schröter
• 金额: --
• 依托单位: Abteilung Systemische Zellbiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/441798639?language=en
• 关键词: Regulation; transcription; cell; identity; FGF

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.

从祖细胞分化成专门的细胞类型是胚胎发育和维持成体周期组织的基础。细胞外信号传导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重要作用。这些信号系统如何将定量信息从质膜传递到转录机器仍然知之甚少。我们解决这个问题的背景下，成纤维细胞生长因子（FGF）信号通过细胞外调节激酶（ERK）在胚胎干细胞（ESC）。FGF/ERK信号在ESC体外分化的最早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过程中的功能。我们将利用ESC系统的成像方法的可访问性，以阐明从FGF受体到靶基因转录的忠实信息传递的转录和信号动力学的作用。具体来说，我们将测试的假设，ERK的动态激活模式编码的配体丰度，可以通过转录机器解码的信息。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。