Objectif Work over the last decade has shown that the genetic programs underlying cell identity are still plastic in terminally differentiated cells. Direct lineage reprogramming takes advantage of this plasticity to induce cell fate conversions from one cell type into another. This is achieved by forced expression of specific fate determinants, usually transcription factors that regulate cell fate during development. This proposal will allow me to address the fundamental biological question whether human glia can be reprogrammed within a human tissue setting, and if so, whether this depends on their state of maturation. I propose to study the possibility of converting human glia into induced neurons within an in vivo-like tissue context. Towards this I will employ cutting-edge techniques such as generation of cerebral organoids from human induced pluripotent stem cells (hiPSCs) and genome-editing techniques to allow for inducible expression of reprogramming factors in human glia at different maturation stages within the cerebral organoids. In order to perform the hiPSCs genome-editing I will use CRISPR/Cas9 technology which will permit me to obtain stable, cell-type specific and inducible hiPSC lines. This novel and valuable genome editing strategy will facilitate the use of different reprogramming factors sets in order to optimize the reprogramming of glial cells into functional neurons. This study may pave the way for translating direct lineage reprogramming into new strategies for brain repair. Champ scientifique medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsgenomes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Thème(s) MSCA-IF-2016 - Individual Fellowships Appel à propositions H2020-MSCA-IF-2016 Voir d’autres projets de cet appel Régime de financement MSCA-IF-EF-ST - Standard EF Coordinateur UNIVERSITAETSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAET MAINZ Contribution nette de l'UE € 171 460,80 Adresse Langenbeckstrasse 1 55131 Mainz Allemagne Voir sur la carte Région Rheinland-Pfalz Rheinhessen-Pfalz Mainz, 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 € 171 460,80
