Fate Map Switching Of Embryonic Senescent Cells And Macrophage-like Cells In Atherosclerosis

Cell senescence plays a vital role in biological process.Recently,some researches reported embryonic senescent cells are also important for embryonic development and tissue organization.The results of SA-?-Gal staining showed the embryonic senescent cells would be cleared during embryonic development.However,as lack of lineage tracing data,the fate mapping of senescent cells in vivo is not validated.Here,we used P21-Cre ER and P21-td Tomato mice to study the fate mapping of senescent cells in embryonic stage.The results show that embryonic senescent cells aren't cleared during development.Otherwise,part of them are reversed and re-entered to cell cycle,What's more,they can contribute to tissues after birth.This study is the first one reveals the plasticity of senescent cells in vivo and provides new directions for curing diseases caused by senescent cells.Smooth muscle cell undergo proliferation and migration into plaque in atherosclerosis.Some researches have suggested that parts of SMCs lost smooth muscle cells' signatures and underwent fate map switching.Recently,the evidence that SMCs can convert to macrophage-like cells was provided by several studies.But the fate mapping of SMCs-derived macrophage-like cells is not clear,as there is no tools to figure out it.Here,we generate two orthogonal recombination systems specifically labeled SMCs-derived macrophage-like cells in AS to study the fates of these cells.Our results reveal that some SMCs-derived macrophage-like cells could revert to smooth muscle cells in fibrous cap and contribute to fibroblasts and pericytes,except some cells still express macrophage markers,proving that these cells are multipotent.This study is the first one reveals the fate mapping of macrophage-like cells and further figures out the process of atherogenesis,providing several potential new targets for curing and ameliorating atherosclerosis.