Identification and successful negotiation of a metabolic checkpoint in direct neuronal reprogramming

ABSTRACT: Despite the widespread interest in direct neuronal reprogramming, the mechanisms underpinning fate conversion remain largely unknown. Our study revealed a critical time point after which cells either successfully convert into neurons or succumb to cell death. Co-transduction with Bcl-2 greatly improved negotiation of this critical point by faster neuronal differentiation. Surprisingly, mutants with reduced or no affinity for Bax demonstrated that Bcl-2 exerts this effect by an apoptosis-independent mechanism. Consistent with a caspase-independent role, ferroptosis inhibitors potently increased neuronal reprogramming by inhibiting lipid peroxidation occurring during fate conversion. Genome-wide expression analysis confirmed that treatments promoting neuronal reprogramming elicit an anti-oxi

ORGANISM(S): Mus musculus

SUBMITTER: Johannes Beckers 

PROVIDER: E-GEOD-70921 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress