The transcription factor C/EBPβ promotes vascular endothelial growth factor A expression and neural stem cell expansion

Abstract

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.

Keywords: C/EBPβ; CHOP-10; VEGF-A; bZIP; neural stem cell.