Objective It is now widely accepted that tumors are composed of heterogeneous population of cells, which contributeto many aspects of treatment resistance observed in clinic. Despite the acknowledgment of the tumor cellheterogeneity, little evidence was shown about complexity and dynamics of this heterogeneity in vivo,mainly because of lacking flexible genetic tools which allow sophisticated analysis in primary tumors. Werecently developed a very efficient mouse somatic brain tumor model which have a full penetrance of highgrade glioma development. Combination of this model with several transgenic mouse lines allow us toisolate and track different population of cells in primary tumors, most importantly, we also confirmed thatthis can be done on single cell level. Here I propose to use this set of valuable genetic tools to dissect thecellular heterogeneity in mouse gliomas. First we will perform several single cell lineage tracing experimentto demonstrate the contribution of brain tumor stem cell, tumor progenitors as well as the relativelydifferentiated cells, which will provide a complete data sets of clonal dynamics of different tumor cell types.Second we will further perform this tracing experiment with the presence of conventional chemotherapy.Third we will perform single cell RNA sequencing experiment to capture the molecular signature, whichdetermines the cellular heterogeneity, discovered by single cell tracing. This result will be further validatedby analysis of this molecular signatures in human primary tumors. We will also use our established in vivotarget validation approach to manipulate the candidate molecular regulators to establish the functionalcorrelation between molecular signature and phenotypic heterogeneity. This project will greatly improve ourunderstanding of tumor heterogeneity, and possibly provide novel approaches and strategies of targetinghuman glioblastomas. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsRNA Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Net EU contribution € 2 000 000,00 Address IM NEUENHEIMER FELD 280 69120 Heidelberg Germany See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 000 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG Germany Net EU contribution € 2 000 000,00 Address IM NEUENHEIMER FELD 280 69120 Heidelberg See on map Region Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 000 000,00
