Objective 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. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsRNA Keywords Hematopoiesis fetal liver lineage tracing cellular barcoding Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-STG - ERC Starting Grant Call for proposal ERC-2016-STG See other projects for this call Funding Scheme ERC-STG - Starting Grant Host institution LUNDS UNIVERSITET Net EU contribution € 1 499 905,00 Address Paradisgatan 5c 22100 Lund Sweden See on map Region Södra Sverige Sydsverige Skåne län 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 Total cost € 1 499 905,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all LUNDS UNIVERSITET Sweden Net EU contribution € 1 499 905,00 Address Paradisgatan 5c 22100 Lund See on map Region Södra Sverige Sydsverige Skåne län 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 Total cost € 1 499 905,00
