Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming

Gascon S, Murenu E, Masserdotti G, Ortega F, Russo GL, Petrik D, Deshpande A, Heinrich C, Karow M, Robertson SP, Schroeder T, Beckers J, Irmler M, Berndt C, Angeli JPF, Conrad M, Berninger B, Goetz M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Cell Stem Cell Elsevier (Cell Press)

Book Volume: 18

Pages Range: 396-409

Journal Issue: 3

DOI: 10.1016/j.stem.2015.12.003

Abstract

Summary 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, co-expression of Bcl-2 and anti-oxidative treatments leads 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.

Involved external institutions

Ludwig-Maximilians-Universität (LMU) DE Germany (DE) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Deutsches Zentrum für Diabetesforschung e.V. (DZD) DE Germany (DE) University of Otago NZ New Zealand (NZ)

How to cite

APA:

Gascon, S., Murenu, E., Masserdotti, G., Ortega, F., Russo, G.L., Petrik, D.,... Goetz, M. (2016). Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming. Cell Stem Cell, 18(3), 396-409. https://dx.doi.org/10.1016/j.stem.2015.12.003

MLA:

Gascon, Sergio, et al. "Identification and Successful Negotiation of a Metabolic Checkpoint in Direct Neuronal Reprogramming." Cell Stem Cell 18.3 (2016): 396-409.

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