Single-Cell Multimodal Profiling Reveals a Novel CD26⁺ Fibroblast Subpopulation in Atherosclerosis-Brief Report

Area of Science:

• Cardiovascular Biology
• Cellular and Molecular Medicine
• Immunology

Background:

• Atherosclerosis pathogenesis involves complex cellular interactions, with fibroblasts being underexplored.
• Understanding fibroblast heterogeneity is crucial for elucidating their roles in plaque development and stability.

Purpose of the Study:

• To comprehensively profile fibroblast diversity in atherosclerosis using a mouse model.
• To characterize fibroblast phenotypes across distinct stages of disease progression.

Main Methods:

• Utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) for multiomic profiling.
• Employed an atherogenic diet in mice over 26 weeks to model atherosclerosis.
• Applied flow cytometry and immunohistochemistry for cell identification and localization.

Main Results:

• Identified 4 distinct fibroblast subpopulations, including a myofibroblast-like subset.
• Discovered CD26 as a specific marker for a fibroblast subpopulation.
• Observed CD26+ fibroblasts migrating from the adventitia to the intima, localizing within the fibrous cap during disease progression.

Conclusions:

• Fibroblast populations exhibit phenotypic diversity and dynamic changes in atherosclerosis.
• CD26+ fibroblasts represent a distinct subpopulation expanding within atherosclerotic lesions.
• These CD26+ fibroblasts may contribute to plaque stability by migrating to the fibrous cap.