Objective Hematopoiesis is an important model for stem cell differentiation with great medical significance.Heterogeneity within hematopoietic progenitor populations has considerably limited characterization andmolecular understanding of lineage commitment in both health and disease. Advances in single-cell genomictechnologies provide an extraordinary opportunity for unbiased and high resolution mapping of biologicalfunction and regulation. Recently we have developed an experimental and analytical method, termedmassively parallel single-cell RNA-Seq (MARS-Seq), for unbiased classification of individual cells fromtheir native context and successfully applied it for characterization of immune and hematopoieticprogenitors.Here, we propose to uncover the hierarchy and regulatory mechanisms controlling hematopoiesis bycombining comprehensive single-cell RNA-Seq analyses, modelling approaches, advanced functional assays,single-cell CRISPR screens, knockout models and epigenetic profiling. Exciting preliminary result show thatindeed our approach is starting to uncover the complexity of hematopoietic progenitors and the regulatorycircuits driving hematopoietic decisions. We will pursue the following aims: (i) Generate a refined model ofhematopoiesis by comprehensive single-cell RNA-Seq profiling of hematopoietic progenitors, (ii) validatethe predicted model by in vivo functional developmental assays and then (iii) test candidate transcription andchromatin factors uncovered by our model for their role in controlling progression towards various lineagesusing single-cell measurements combined with CRISPR screens. Together, our study is expected to generatea revised and high-resolution hematopoietic model and decipher the regulatory networks that controlhematopoiesis. Our methods and models may provide a platform for future medical advancements includinga large-scale European collaborative project to discover a comprehensive human hematopoietic tree. Fields of science natural sciencesbiological sciencesgeneticsmedical and health sciencesmedical biotechnologycells technologiesstem cells Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-COG - ERC Consolidator Grant Call for proposal ERC-2016-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Coordinator WEIZMANN INSTITUTE OF SCIENCE Net EU contribution € 2 000 000,00 Address Herzl street 234 7610001 Rehovot Israel See on map Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all WEIZMANN INSTITUTE OF SCIENCE Israel Net EU contribution € 2 000 000,00 Address Herzl street 234 7610001 Rehovot See on map Activity type Higher or Secondary Education Establishments 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 Other funding € 0,00
