In:
The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 166.39-166.39
Abstract:
Atherosclerosis is a leading cause of death worldwide in industrialized countries. We have previously shown that disease progression and regression are strongly associated with the M1/M2 activation status of macrophages derived from inflammatory monocytes in the plaques with large differences in transcriptional profiles. However, the features of monocyte to macrophage transitions during either plaque progression or regression are poorly understood. Here, we use a combination of single-cell RNA sequencing and tamoxifen-inducible fate mapping approaches to profile 3157 and 2198 arterial cells derived from CX3CR1+ precursor in atherosclerotic mice during plaque progression and regression. There was surprising heterogeneity among the cell populations, despite derivation from a common precursor. We compared the distinct cell clusters with the IMMGEN database to define each population and then used pseudo-time analysis to model the differentiation process from monocyte precursors to activated macrophages under progression and regression conditions. Notably, distinct cell clusters with a type 1 interferon (IFN) signature was observed during progression, which was significantly rare in regression. Whereas a unique cluster in regression was marked by increased expression of various heat shock proteins (HSP). Overall, this study highlights previously unidentified genes and programs in macrophages associated with atherosclerosis progression and regression, uncovering the unexpected plasticity of CX3CR1+ monocyte derived cells.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.200.Supp.166.39
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2018
detail.hit.zdb_id:
1475085-5
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