Intravital multiphoton imaging and single cell RNA-Seq of monocyte-derived cells in atherosclerotic lesions.

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Atherosclerosis is a leading cause of heart attack or stroke and clearly shows an immunological aspect in the pathogenesis. The new recently developed in the Ley lab provides intravital 4D high-resolution imaging of leukocyte behaviour in atherosclerotic plaque in an unprecedented manner. This project aims to identify new cellular migration/interaction patterns and their molecular mechanisms in the context of atherogenesis. Single cell next-generation sequencing of monocytes will be employed to identify new key molecules for plaque homing and lineage commitment, e.g. transcription factors. By bone marrow transplantation, adoptive transfer experiments and multicolor flow cytometry we aim to characterize the role of new target molecules in monocyte differentiation and subset composition in the plaque. Cell-cell interactions and migration patterns of identified monocyte subsets will be studied in situ using ILTIS. The identification of molecular switches in atherogenesis could provide new targets for prevention and therapy of atherosclerosis.