Gizem Inak, Agnieszka Rybak-Wolf, Pawel Lisowski, Tancredi M Pentimalli, René Jüttner, Petar Glažar, Karan Uppal, Emanuela Bottani, Dario Brunetti, Christopher Secker, Annika Zink, David Meierhofer, Marie-Thérèse Henke, Monishita Dey, Ummi Ciptasari, Barbara Mlody, Tobias Hahn, Maria Berruezo-Llacuna, Nikos Karaiskos, Michela Di Virgilio, Johannes A Mayr, Saskia B Wortmann, Josef Priller, Michael Gotthardt, Dean P Jones, Ertan Mayatepek, Werner Stenzel, Sebastian Diecke, Ralf Kühn, Erich E Wanker, Nikolaus Rajewsky, Markus Schuelke, Alessandro Prigione
Leigh syndrome (LS) is a severe manifestation of mitochondrial disease in children and is currently incurable. The lack of effective models hampers our understanding of the mechanisms underlying the neuronal pathology of LS. Using patient-derived induced pluripotent stem cells and CRISPR/Cas9 engineering, we developed a human model of LS caused by mutations in the complex IV assembly gene SURF1. Single-cell RNA-sequencing and multi-omics analysis revealed compromised neuronal morphogenesis in mutant neural cultures and brain organoids...
March 26, 2021: Nature Communications