Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression
Journal
JCI insight
Journal Volume
4
Journal Issue
4
Pages
1-15
Date Issued
2019
Author(s)
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.
Subjects
Atherosclerosis; Cardiology; Immunology; Macrophages; Molecular diagnosis
Other Subjects
chemokine receptor CX3CR1; Cx3cr1 protein, mouse; low density lipoprotein receptor; adverse event; animal; atherosclerosis; atherosclerotic plaque; bone marrow transplantation; cell differentiation; disease exacerbation; disease model; genetics; histocompatibility; human; immunology; knockout mouse; macrophage; macrophage activation; metabolism; monocyte macrophage precursor cell; mouse; pathology; physiology; signal transduction; single cell analysis; Western diet; Animals; Atherosclerosis; Bone Marrow Transplantation; Cell Differentiation; CX3C Chemokine Receptor 1; Diet, Western; Disease Models, Animal; Disease Progression; Humans; Macrophage Activation; Macrophages; Mice; Mice, Knockout; Monocyte-Macrophage Precursor Cells; Plaque, Atherosclerotic; Receptors, LDL; RNA-Seq; Signal Transduction; Single-Cell Analysis; Transplantation Chimera
Publisher
American Society for Clinical Investigation
Type
journal article