"Dendritic cells, essential mediators of immunity and tolerance, are not a homogeneous cell type, but display a multitude of different functions and phenotypes. While the heterogeneity in phenotype and function of dendritic cells has been well described, our understanding of the in vivo origin of different dendritic cells subsets is still limited. Identification of the cellular intermediates on their way to dendritic cell differentiation will form an essential step to understand the dynamic regulation of the number, localization, and functionality of these cells and should contribute to the development of vaccination and immunotherapy strategy that rely on dendritic cells.
The objectives of this project are to elucidate the genealogy of dendritic cells in vivo. To this purpose, I plan to use two complementary approaches. First, I will measure the fate of individual dendritic cells progenitors by the new experimental technology of barcoding that allows the tracing of a large number of individual cells in vivo. As the data obtained from barcoding experiments require mathematical modeling for proper interpretation, I will then develop a modeling approach to analyze the data. The results obtained in this project should yield a map of dendritic cells development in vivo under both steady state conditions and during infection.
This cross-disciplinary approach to analyze dendritic cell commitment that I propose here should lead to a description of the genealogy of dendritic cell subsets, while at the same time providing a conceptual framework to analyze lineage differentiation issues for other cell types."
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