A common integrative nuclear signaling module for stem cell development

Ontogeny requires the coordinated regulation of multi-gene programs by a plethora of extracellular and intracellular signals. As a result of gene regulation, stem cells alternate between states of self-renewal and differentiation. Disruption of this regulation may cause oncogenic transformation in which stem cells are “arrested” in the proliferative state. The emerging principles of systems biology suggest that computational network modules are responsible for the integration of epigenetic signals that determine specific developmental stages. Modules that control entry into cell cycle and promote perpetual self-renewal of the stem cells have been identified. In this chapter, we summarize the current understanding of a novel Feed-Forward-And-Gate network module that affects the differentiation of stem cells and neural progenitor cells. In the center of this module is the new gene controlling mechanism — integrative nuclear fibroblast growth factor receptor (FGFR)-1 signaling (INFS). Enhancement of the INFS may be used to reestablish coordinated gene regulation to activate cell differentiation for regenerative purposes or to provide interruption of cancer stem cell proliferation.