Ascl1 phospho-site mutations enhance neuronal conversion of adult cortical astrocytes in vivo.

ABSTRACT: Direct neuronal reprogramming, the process whereby a terminally differentiated cell is converted into an induced neuron without traversing a pluripotent state, has tremendous therapeutic potential for a host of neurodegenerative diseases. While there is strong evidence for astrocyte-to-neuron conversion in vitro, in vivo studies in the adult brain are less supportive or controversial. Here, we set out to enhance the efficacy of neuronal conversion of adult astrocytes in vivo by optimizing the neurogenic capacity of a driver transcription factor encoded by the proneural gene Ascl1. Specifically, we mutated six serine phospho-acceptor sites in Ascl1 to alanines (Ascl1 ^{SA 6}) to prevent phosphorylation by proline-directed serine/threonine kinases. Nat

SUBMITTER: Ghazale H 

PROVIDER: S-EPMC9434350 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature