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

动脉粥样硬化是心脏病发作或中风的主要原因，在发病机制中清楚地显示出免疫方面的作用。Ley实验室最近开发的新技术以前所未有的方式提供了动脉粥样硬化斑块中白细胞行为的活体4D高分辨率成像。本项目旨在确定动脉粥样硬化背景下新的细胞迁移/相互作用模式及其分子机制。下一代单核细胞单细胞测序将用于鉴定斑块归巢和谱系承诺的新关键分子，例如转录因子。通过骨髓移植，过继性转移实验和多色流式细胞术，我们旨在表征新的靶分子在单核细胞分化和斑块亚群组成中的作用。细胞间相互作用和迁移模式鉴定单核细胞亚群将在原位研究使用ILTIS。发现动脉粥样硬化发生过程中的分子开关可以为动脉粥样硬化的预防和治疗提供新的靶点。

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.