1. Single-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression
- Author
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Jordan Poles, Hitoo Nishi, Caroline S McCauley, Stephen A. Ramsey, Stephen T. Yeung, Ada Weinstock, Karishma Rahman, P'ng Loke, Xiang Niu, Edward A. Fisher, Jian-Da Lin, Emily J. Brown, and Nikollaq Vozhilla
- Subjects
0301 basic medicine ,CX3C Chemokine Receptor 1 ,Biology ,Monocyte-Macrophage Precursor Cells ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Single-cell analysis ,Fate mapping ,CX3CR1 ,Macrophage ,Animals ,Humans ,RNA-Seq ,Bone Marrow Transplantation ,Mice, Knockout ,Transplantation Chimera ,Transition (genetics) ,Macrophages ,RNA ,Cell Differentiation ,General Medicine ,M2 polarization ,Macrophage Activation ,Atherosclerosis ,Regression ,Plaque, Atherosclerotic ,Disease Models, Animal ,030104 developmental biology ,Receptors, LDL ,Diet, Western ,030220 oncology & carcinogenesis ,Cancer research ,Disease Progression ,Single-Cell Analysis ,Signal Transduction ,Research Article - 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.
- Published
- 2018