Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Gascón, Sergio, Murenu, Elisa, Masserdotti, Giacomo, Ortega, Felipe, Russo, Gianluca L., Petrik, David, Deshpande, Aditi, Heinrich, Christophe, Karow, Marisa, Robertson, Stephen P., Schroeder, Timm, Beckers, Johannes, Irmler, Martin, Berndt, Carsten, Angeli, José P. Friedmann, Conrad, Marcus, Berninger, Benedikt and Götz, Magdalena 2016. Identification and successful negotiation of a metabolic checkpoint in direct neuronal reprogramming. Cell Stem Cell 18 (3) , pp. 396-409. 10.1016/j.stem.2015.12.003

[img]
Preview
PDF - Accepted Post-Print Version
Download (4MB) | Preview

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, 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Elsevier
ISSN: 1934-5909
Date of First Compliant Deposit: 11 September 2019
Date of Acceptance: 10 December 2015
Last Modified: 18 Oct 2019 14:28
URI: http://orca.cf.ac.uk/id/eprint/125397

Citation Data

Cited 100 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics