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.

C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease

“…C/EBPβ exhibits elevated expression levels within the hippocampus, cortex, and cerebellum, correlating significantly with neuronal developmental processes. During central nervous system (CNS) development, in addition to playing multiple roles in diverting cortical precursors to neuronal fate and benefiting neurogenesis, the expression of C/EBPβ in the adult hippocampus has been shown to be primarily localized in the nucleus of granular neurons of the dentate gyrus and to play a key role in regulating the proliferation and differentiation of these cells in vitro and in vivo 25–27 . The comprehensive investigation of C/EBPβ's cellular and subcellular localization in the healthy CNS is yet to be undertaken.…”

“…primarily localized in the nucleus of granular neurons of the dentate gyrus and to play a key role in regulating the proliferation and differentiation of these cells in vitro and in vivo. [25][26][27] The comprehensive investigation of C/EBPβ's cellular and subcellular localization in the healthy CNS is yet to be undertaken. Notably, C/EBPβ has been directly associated with the progression of AD in humans.…”