Deep Phenotyping by Mass Cytometry and Single-Cell RNA-Sequencing Reveals LYN-Regulated Signaling Profiles Underlying Monocyte Subset Heterogeneity and Lifespan.

Circulation Research
Morgan E RobertsKenneth W Harder

Abstract

Monocytes are key effectors of the mononuclear phagocyte system, playing critical roles in regulating tissue homeostasis and coordinating inflammatory reactions, including those involved in chronic inflammatory diseases such as atherosclerosis. Monocytes have traditionally been divided into 2 major subsets termed conventional monocytes and patrolling monocytes (pMo) but recent systems immunology approaches have identified marked heterogeneity within these cells, and much of what regulates monocyte population homeostasis remains unknown. We and others have previously identified LYN tyrosine kinase as a key negative regulator of myeloid cell biology; however, LYN's role in regulating specific monocyte subset homeostasis has not been investigated. We sought to comprehensively profile monocytes to elucidate the underlying heterogeneity within monocytes and dissect how Lyn deficiency affects monocyte subset composition, signaling, and gene expression. We further tested the biological significance of these findings in a model of atherosclerosis. Mass cytometric analysis of monocyte subsets and signaling pathway activation patterns in conventional monocytes and pMos revealed distinct baseline signaling profiles and far greater heterog...Continue Reading

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Citations

May 8, 2020·Circulation Research·Rajat M GuptaPeter Libby
Jun 29, 2021·Frontiers in Cardiovascular Medicine·Mengxia Fu, Jiangping Song
Oct 30, 2021·Frontiers in Cell and Developmental Biology·Ramona VinciGiovanna Liuzzo

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Methods Mentioned

BETA
RNA-seq
flow cytometry
dissections

Software Mentioned

R
pMos
SAM
CyTOF
cMos
ACCENSE

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