Objectif FateMapB aims to understand how the unique differentiation potential of fetal hematopoietic stem and progenitor cells(HSPCs) contribute to functionally distinct cell types of the adult immune system. While most immune cells are replenishedby HSPCs through life, others emerge during a limited window in fetal life and sustain through self-renewal in situ. Thelineage identity of fetal HSPCs, and the extent of their contribution to the adult immune repertoire remain surprisinglyunclear. I previously identified the fetal specific RNA binding protein Lin28b as a post-transcriptional molecular switchcapable of inducing fetal-like hematopoiesis in adult bone marrow HSPCs (Yuan et al. Science, 2012). This discovery hasafforded me with unique perspectives on the formation of the mammalian immune system. The concept that the matureimmune system is a mosaic of fetal and adult derived cell types is addressed herein with an emphasis on the B cell lineage.We will use two complementary lineage-tracing technologies to stratify the immune system as a function of developmentaltime, generating fundamental insight into the division of labor between fetal and adult HSPCs that ultimately provideseffective host protection.Aim 1. Determine the qualitative and quantitative contribution of fetal HSPCs to the mature immune repertoire in situthrough Cre recombination mediated lineage-tracing.Aim 2. Resolve the disputed lineage relationship between fetal derived B1a cells and adult derived B2 cells by single celllineage-tracing using cellular barcoding in vivo.Aim 3. Characterize the mechanism and effector functions of Lin28b induced B1a cell development for assessing theclinical utility of inducible fetal-like lymphopoiesis.The implications of FateMapB extend beyond normal development to immune regeneration and age-related features ofleukemogenesis. Finally, our combinatorial lineage-tracing approach enables dissection of cell fates with previouslyunattainable resolution. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNA Mots‑clés Hematopoiesis fetal liver lineage tracing cellular barcoding Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-2016-STG - ERC Starting Grant Appel à propositions ERC-2016-STG Voir d’autres projets de cet appel Régime de financement ERC-STG - Starting Grant Institution d’accueil LUNDS UNIVERSITET Contribution nette de l'UE € 1 499 905,00 Adresse Paradisgatan 5c 22100 Lund Suède Voir sur la carte Région Södra Sverige Sydsverige Skåne län 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 € 1 499 905,00 Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire LUNDS UNIVERSITET Suède Contribution nette de l'UE € 1 499 905,00 Adresse Paradisgatan 5c 22100 Lund Voir sur la carte Région Södra Sverige Sydsverige Skåne län 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 € 1 499 905,00