Contribution of Embryonic MACrophages in stem cell dependent hematopoiesis – EMAC

The innate immune cells called macrophages constitute prime actors at the interface amongst tissues as well as between the organism and the environment. They protect us from external/internal insults and recent studies demonstrate that they also affect patterning, tissue reshaping and metabolism. Moreover, their impact in cancer, neurodegeneration and ageing, makes them potential therapeutic targets.
The macrophages that populate the adult tissues are born from hematopoietic waves that are distinct for their mode of differentiation (stem cell independent or independent), their spatial localization and the developmental stage at which they occur. The role of the early waves (which are stem cell independent) in development and physiology starts being recognized, as these cells with migratory potential may facilitate the interactions amongst tissues as well as the responses to the nutritional and environmental changes faced by the organism from its birth. Unfortunately, we lack a comprehensive view because cell-specific tools have been scarce.
Based on tools recently developed in our laboratories and our preliminary data, we will test the hypothesis that the early hematopoietic waves play a crucial role in late, stem cell dependent, hematopoiesis. The two complementary animal models available in our laboratories will allow us to focus on evolutionarily conserved pathways and hence leverage the resources, the approaches and the impact of the obtained results. Our multidisciplinary in vivo, ex vivo and in vitro approach relies on high throughput techniques, mathematical modeling, artificial intelligence and bioinformatics as well as on classical genetic, molecular and cell biology techniques.
This combination of expertise and approaches will make it possible to reach an integrated view on the interactions between the hematopoietic waves, their role and the underlying molecular mechanisms. A better understanding of the biology of the early born macrophages will benefit a large scientific community and has a clear medical potential, especially in human pathologies of developmental origin.