3012 – CONTRIBUTION OF ERYTHROMYELOID PROGENITOR- AND HEMATOPOIETIC STEM CELL-DERIVED NEUTROPHILS TO THE DEVELOPING MOUSE HEMATOPOIETIC SYSTEM

Neutrophils play a critical role in host defence, especially in neonates whose immune systems are not yet fully developed. In the fetus, neutrophils originate from at least two origins: yolk sac-derived erythromyeloid progenitors (EMPs) and aorta-derived hematopoietic stem cells (HSCs). In zebrafish, developmentally discrete neutrophil populations were associated with different functions, leading us to hypothesize that also in mammals developmentally distinct neutrophils may have discrete functions and/or gestational stage-specific contributions to the hematopoietic system. To explore this, we have used lineage tracing to establish a spatiotemporal map of EMP- and HSC-derived neutrophils during mouse fetal and neonatal development. We observe a dynamic shift in the contribution of developmentally distinct neutrophil lineages over the fetal and neonatal period, with specific changes in the precursor neutrophil subset in the liver, spleen and bone marrow. The contribution of EMP-derived neutrophils significantly dropped by embryonic day (E) 18.5. Transcriptomic analysis of neutrophils isolated from E18.5 bone marrow inferred three mature, yet functionally distinct, subsets, with gene set enrichment analysis (GSEA) indicating conventional, anti-viral and regulatory functions. Transcriptomic and functional analysis of EMP- and HSC-derived neutrophils is ongoing. These studies will yield basic insights into fetal and neonatal neutrophil biology and serve as a benchmark for further translational studies.