Filter and export

Publications

What is a Publication?
1 Publication visible to you, out of a total of 1
Direct neuronal reprogramming of NDUFS4 patient cells identifies the unfolded protein response as a novel general reprogramming hurdle.

Abstract (Expand)

Mitochondria account for essential cellular pathways, from ATP production to nucleotide metabolism, and their deficits lead to neurological disorders and contribute to the onset of age-related diseases. … Direct neuronal reprogramming aims at replacing neurons lost in such conditions, but very little is known about the impact of mitochondrial dysfunction on the direct reprogramming of human cells. Here, we explore the effects of mitochondrial dysfunction on the neuronal reprogramming of induced pluripotent stem cell (iPSC)-derived astrocytes carrying mutations in the NDUFS4 gene, important for Complex I and associated with Leigh syndrome. This led to the identification of the unfolded protein response as a major hurdle in the direct neuronal conversion of not only astrocytes and fibroblasts from patients but also control human astrocytes and fibroblasts. Its transient inhibition potently improves reprogramming by influencing the mitochondria-endoplasmic-reticulum-stress-mediated pathways. Taken together, disease modeling using patient cells unraveled novel general hurdles and ways to overcome these in human astrocyte-to-neuron reprogramming.

Authors: G. Sonsalla, A. B. Malpartida, T. Riedemann, M. Gusic, E. Rusha, G. Bulli, S. Najas, A. Janjic, B. A. Hersbach, P. Smialowski, M. Drukker, W. Enard, J. H. M. Prehn, H. Prokisch, M. Gotz, G. Masserdotti

Date Published: 3rd Apr 2024

Publication Type: Journal

Powered by
 (v.1.15.0)
About FAIRDOM | About SyNergy - Cluster for Systems Neurology | Funding and Programmes | Credits
Copyright © 2008 - 2024 The University of Manchester and HITS gGmbH