TitleSingle-cell analysis of fate-mapped macrophages reveals heterogeneity, including stem-like properties, during atherosclerosis progression and regression.
Publication TypeJournal Article
Year of Publication2019
AuthorsDa Lin, J-, Nishi, H, Poles, J, Niu, X, Mccauley, C, Rahman, K, Brown, EJ, Yeung, ST, Vozhilla, N, Weinstock, A, Ramsey, SA, Fisher, EA, Loke, P'ng
JournalJCI Insight
Date Published2019 02 21
KeywordsAnimals, 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

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.

Alternate JournalJCI Insight
PubMed ID30830865
PubMed Central IDPMC6478411
Grant ListR01 AI133977 / AI / NIAID NIH HHS / United States
R01 HL084312 / HL / NHLBI NIH HHS / United States