The bZIP transcription factor CCAAT‐enhancer‐binding protein β (C/EBPβ) exhibits neurogenic, neuritogenic, and pro‐survival effects in the central nervous system. Here, we show that C/EBPβ regulates neural stem cell (NSC) expansion and vascular endothelial growth factor A (VEGF‐A) level by acting on a C/EBPβ‐responsive element within the Vegf‐a promoter. As predicted, C/EBPβ depletion reduced VEGF‐A production, NSC number, and average neurosphere size in proliferating cultures. Conversely, deletion of the C/EBPβ repressor CHOP‐10 induced C/EBPβ and VEGF‐A expression, while stimulating NSC expansion. These data highlight the role of C/EBPβ in regulating VEGF‐A production and the growth of NSCs and suggest CHOP‐dependent antagonism of C/EBPβ may function as a transcriptional rheostat linking stress‐associated cues with stem cell quiescence among other pathological responses affecting the neurogenic niche.

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