Objectif The discovery of pluripotent stem cells has expanded the working modes in biology towards the reverse engineering of specific cell types. Unlike studying developmental phenomena in vivo, we are now theoretically able to mimic some of these processes in a dish. The use of human induced pluripotent stem (iPS) cells facilitates studying the genesis of human cell types in an ethically approved setting. However, exploiting the full potency of stem cells is only possible with very few differentiated cell types. In particular, the generation of neurons is in its infancy: of the many neuronal types present in the brain, only a few types have been generated in vitro. So far, neuronal differentiation protocols are multifaceted and tailored to individual cell types. The molecular events that occur during reprogramming remain enigmatic. Hence, we cannot confer these protocols easily on producing different neurons of interest. Therefore, we plan to induce transcription factors as differentiation control buttons in human iPS cells in order to explore in vitro neurogenesis systematically. First, we will apply a human transcription factor library to conditional fluorescent iPS reporter lines, facilitating high-throughput isolation and analysis of induced neurons. Second, the underlying gene regulatory networks will be revealed using RNA-sequencing over the entire differentiation period to identify the biological rules of in vitro neuronal differentiation. We will combine these in-depth transcriptomic analyses with morphological, anatomical, and functional characterizations. Finally, based on our discoveries, we will engineer human photoreceptors that can be applied to cell transplantation experiments in retinal degeneration diseases. Conceptually, our approach paves the way for targeted “forward” programming of human iPS cells to neurons. Champ scientifique medical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencescomputer and information sciencescomputational sciencemedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesgeneticsRNAmedical and health sciencesclinical medicinetransplantation Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-StG-2015 - ERC Starting Grant Appel à propositions ERC-2015-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil TECHNISCHE UNIVERSITAET DRESDEN Contribution nette de l'UE € 1 482 500,00 Adresse HELMHOLTZSTRASSE 10 01069 Dresden Allemagne Voir sur la carte Région Sachsen Dresden Dresden, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 482 500,00 Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire TECHNISCHE UNIVERSITAET DRESDEN Allemagne Contribution nette de l'UE € 1 482 500,00 Adresse HELMHOLTZSTRASSE 10 01069 Dresden Voir sur la carte Région Sachsen Dresden Dresden, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 482 500,00 UNIVERSITATSKLINIKUM BONN Allemagne Contribution nette de l'UE € 12 500,00 Adresse VENUSBERG-CAMPUS 1 53127 Bonn Voir sur la carte Région Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 12 500,00