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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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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-oxidative stress response. Importantly, coexpression of Bcl-2 and anti-oxidative treatments lead to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury in vivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type, in vitro and in vivo. We performed gene expression microarray analysis on mouse embryonic fibroblasts transfected with a viral vector for Ascl1 or empty vector. Cells were then cultured in the absence or presence of forskolin

ORGANISM(S): Mus musculus

SUBMITTER: Johannes Beckers

PROVIDER: E-GEOD-60790 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Project description: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-oxidative stress response. Importantly, coexpression of Bcl-2 and anti-oxidative treatments lead to an unprecedented improvement in glial-to-neuron conversion after traumatic brain injury in vivo, underscoring the relevance of these pathways in cellular reprograming irrespective of cell type, in vitro and in vivo. We performed gene expression microarray analysis on mouse embryonic fibroblasts transfected with a viral vector for Ascl1 or empty vector. Cells were then cultured in the absence or presence of forskolin

2016-06-29 | E-GEOD-70921 | biostudies-arrayexpress

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

2016-06-29 | GSE70921 | GEO

Reprogramming by de-bookmarking somatic transcriptional program via targeting the BET bromodomains

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