Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States

Area of Science:

• Immunology
• Cell Biology
• Genomics

Background:

• Monocytes are key innate immune cells with homeostatic and immunoregulatory roles.
• Historically identified by CD14 and CD16 markers, monocytes are now understood to be highly heterogeneous.
• Recent single-cell studies challenge traditional classifications, revealing a more complex cellular landscape.

Purpose of the Study:

• To comprehensively map the transcriptional and phenotypic diversity of monocytes.
• To identify distinct monocyte subpopulations and their characteristics.
• To investigate monocyte alterations in cardiovascular disease risk factors.

Main Methods:

• Utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing.
• Analyzed a large dataset of 437,126 monocytes.
• Validated findings using flow cytometry.

Main Results:

• Identified diverse monocyte subsets, including IFN-responsive, MHCIIhi, monocyte-platelet aggregates, nonclassical, and classical subpopulations.
• Each subpopulation displayed unique transcriptional regulation, developmental trajectories, and tissue distribution.
• Observed alterations in monocytes linked to cardiovascular disease risk factors like race, smoking, and hyperlipidemia, with hyperlipidemia effects confirmed in mouse models.

Conclusions:

• This integrative analysis offers a novel perspective on monocyte heterogeneity and their role in pathological conditions.
• Provides insights into monocyte-driven cardiovascular disease mechanisms.
• Suggests potential for targeted therapies based on monocyte subpopulations.