Objectif Ageing is accompanied by ectopic white adipose tissue depositions in skeletal muscle and other anatomical locations, such as brown adipose tissue and the bone marrow. Ectopic fat accrual contributes to organ dysfunction, systemic insulin resistance, and other perturbations that have been implicated in metabolic diseases.This research proposal aims to identify the regulatory cues that control the development of ectopic progenitor cells that give rise to this type of fat. It is hypothesized that an age-related dysfunction of the stem cell niche leads to an imbalance between (1) tissue-specific stem cells and (2) fibroblast-like, primarily adipogenic progenitors that reside within many tissues. Novel methodologies that assess stem/progenitor cell characteristics on the single cell level will be combined with animal models of lineage tracing to determine the developmental origin of these adipogenic progenitors and processes that regulate their function.Notch signalling is a key signalling pathway that relies on direct physical interaction to control stem cell fate. It is proposed that impaired Notch activity contributes to the phenotypical shift of precursor cell distribution in aged tissues.Lastly, the role of the stem cell niche in ectopic adipocyte progenitor formation will be analyzed. External signals originating from the surrounding niche cells regulate the developmental fate of stem cells. Secreted factors and their role in the formation of ectopic adipocyte precursors during senescence will be identified using a combination of biochemical and systems biology approaches.Accomplishment of these studies will help to understand the basic processes of stem cell ageing and identify mechanisms of age-related functional decline in tissue regeneration. By targeting the population of tissue-resident adipogenic progenitor cells, therapeutic strategies could be developed to counteract metabolic complications associated with the ageing process. Champ scientifique medical and health sciencesmedical biotechnologycells technologiesstem cells Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Appel à propositions ERC-2012-StG_20111109 Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil DEUTSCHES INSTITUT FUER ERNAEHRUNGSFORSCHUNG POTSDAM REHBRUECKE Contribution de l’UE € 1 496 444,00 Adresse Arthur-Scheunert-Allee 114-116 14558 Nuthetal Allemagne Voir sur la carte Région Brandenburg Brandenburg Potsdam-Mittelmark Type d’activité Research Organisations Chercheur principal Tim Julius Schulz (Dr.) Contact administratif Maria Löwinger (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire DEUTSCHES INSTITUT FUER ERNAEHRUNGSFORSCHUNG POTSDAM REHBRUECKE Allemagne Contribution de l’UE € 1 496 444,00 Adresse Arthur-Scheunert-Allee 114-116 14558 Nuthetal Voir sur la carte Région Brandenburg Brandenburg Potsdam-Mittelmark Type d’activité Research Organisations Chercheur principal Tim Julius Schulz (Dr.) Contact administratif Maria Löwinger (Dr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée