NF-κB Activity Initiates Human ESC-Derived Neural Progenitor Cell Differentiation by Inducing a Metabolic Maturation Program

Human neural development begins at embryonic day 19 and marks the beginning of organogenesis. Neural stem cells in the neural tube undergo profound functional, morphological, and metabolic changes during neural specification, coordinated by a combination of exogenous and endogenous cues. The temporal cell signaling activities that mediate this process, during development and in the postnatal brain, are incompletely understood. We have applied gene expression studies and transcription factor-activated reporter lentiviruses during in vitro neural specification of human pluripotent stem cells. We show that nuclear factor κB orchestrates a multi-faceted metabolic program necessary for the maturation of neural progenitor cells during neurogenesis. In this research article, FitzPatrick and colleagues have highlighted the requirement for NF-κB signaling in neural specification of human embryonic stem cells. They demonstrate that its activity orchestrates a metabolic shift toward oxidative phosphorylation in committing neural progenitor cells. Moreover, they demonstrate that progenitor cells with increased endogenous NF-κB activity have a higher propensity for maturation.