Neural Progenitor Cell Gene Expression In Response To CBP(S436A) mutant

The histone acetyltransferase, CREB binding protein (CBP), is important for appropriate differentiation of neural stem/progenitor cells (NPCs). The serine 436 phosphoryaltion in CBP responds to enviormental cues to promote neuronal differentiaiton of adult NPCs (Fatt, et al, Stem Cell Reports, 5:1-8, 2015; Gouveia, et al., Stem Cell Reports, 11: 719-734, 2016). Here, we have used a phospho-null CBPS436A knock-in (KI) mouse strain to isolate subventricular zone (SVZ) NPCs, which were further expanded and differentiated ex vivo for RNAseq analysis. This allowed us to study underlying molecular mechanisms that mediate CBP Ser436 phosphorylation to promote adult NPC differentiation. Overall design: SVZ NPCs were isolated from 2-month-old CBPS436A-KI and their wild type littermates (n=2/genotype) and expanded ex vivo. At Passage 2 (P2), the NPCs were directed to differentiation medium in the presence of metformin for 6 days. Total RNA from the P2 differentiating NPCs were used for RNA-seq analysis.