Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression
Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression
Abstract
Atherosclerosis is a leading cause of death worldwide in industrialized countries. ==Disease progression and regression are associated with different activation states of macrophages derived from inflammatory monocytes entering the plaques==. The features of monocyte-to-macrophage transition and the full spectrum of macrophage activation states during either plaque progression or regression, however, are incompletely established. Here, we use a combination of single-cell RNA sequencing and genetic fate mapping to profile, for the first time to our knowledge, plaque cells derived from CX3CR1+ precursors in mice during both progression and regression of atherosclerosis. ==The analyses revealed a spectrum of macrophage activation states with greater complexity than the traditional M1 and M2 polarization states, with progression associated with differentiation of CXC3R1+ monocytes into more distinct states than during regression==. We also identified an unexpected cluster of proliferating monocytes with a stem cell–like signature, suggesting that monocytes may persist in a proliferating self-renewal state in inflamed tissue, rather than differentiating immediately into macrophages after entering the tissue.
Results
Figure1
Figure1 shows the gene expression difference between progression and regression group.
Figure2
Figure2 shows the heterogeneity of progression and regression group.
Figure3
Figure3 shows classifications and gene lists of clusters of plaque macrophages derived from CX3CR1+ monocyte precursors in atherosclerosis progression and regression.
Figure4
Figure4 shows pseudotime and principal component analysis identification of genes associated with atherosclerosis progression and regression.
Figure5
Figure5 shows pseudotime scores and related genes associated with atherosclerosis progression and regression.
Figure6
Figure6 shows the identification of a proliferative “stem-like” cell cluster that retains CX3CR1 expression, which is cluster 7.
Figure7
Figure7 shows the validation of the presence of a “stem-like” cell cluster from an independent study of atherosclerotic mice.