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Gascón, S. ; Murenu, E. ; Masserdotti, G. ; Ortega, F.* ; Russo, G.L. ; Petrik, D. ; Deshpande, A.* ; Heinrich, C.* ; Karow, M.* ; Robertson, S.P.* ; Schroeder, T. ; Beckers, J. ; Irmler, M. ; Berndt, C.* ; Friedmann Angeli, J.P.F. ; Conrad, M. ; Berninger, B.* ; Götz, M.

Identification and successful negotiation of a metabolic checkpoint in direct neuronal repogramming.

Cell Stem Cell 18, 396-409 (2016)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Nonapoptotic Cell-death; Oxidative Stress; In-vivo; Brain-injury; Vitamin-d; Mitochondrial Metabolism; Lipid-peroxidation; Functional-neurons; Direct Conversion; Progenitor Cells
ISSN (print) / ISBN 1934-5909
e-ISSN 1875-9777
Zeitschrift Cell Stem Cell
Quellenangaben Band: 18, Heft: 3, Seiten: 396-409 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed