Gouveia, AydenSeegobin, MatthewKannangara, Timal S.He, LingWondisford, FredricComin, Cesar H.Costa, Luciano da F.Béïque, Jean-ClaudeLagace, Diane C.Lacoste, BaptisteWang, Jing2019-04-302019-04-30201722136711https://doi.org/10.20381/ruor-23369http://hdl.handle.net/10393/39121Epigenetic modifications have emerged as attractive molecular substrates that integrate extrinsic changes into the determination of cell identity. Since stroke-related brain damage releases micro-environmental cues, we examined the role of a signaling-induced epigenetic pathway, an atypical protein kinase C (aPKC)-mediated phosphorylation of CREB-binding protein (CBP), in post-stroke neurovascular remodeling. Using a knockin mouse strain (CbpS436A) where the aPKC-CBP pathway was defective, we show that disruption of the aPKC-CBP pathway in a murine focal ischemic stroke model increases the reprogramming efficiency of ischemia-activated pericytes (i-pericytes) to neural precursors. As a consequence of enhanced cellular reprogramming, CbpS436A mice show an increased transient population of locally derived neural precursors after stroke, while displaying a reduced number of i-pericytes, impaired vascular remodeling, and perturbed motor recovery during the chronic phase of stroke. Together, this study elucidates the role of the aPKC-CBP pathway in modulating neurovascular remodeling and functional recovery following focal ischemic stroke.enaPKC-CBP pathwaycellular reprogrammingischemic strokeneural precursorspericytevascular remodelingAnimalsBrain IschemiaCREB-Binding ProteinCellular ReprogrammingMiceNeurogenesisPericytesPhosphorylationProtein Kinase CRecovery of FunctionSignal TransductionStrokeStroke RehabilitationVascular RemodelingArticle10.1016/j.stemcr.2017.10.021