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Single-cell and spatial analysis reveals the interaction between ITLN1+ foam cells and SPP1+ macrophages in
Ying Li1,2, Shanshan Wang3, Ruidan Zhang1,2
1Department of Pharmaceutical Sciences, Institute of Pharmacology, Zhejiang University of Technology, Hangzhou, China.
Insights
This study reveals that interactions between vascular smooth muscle cell-derived foam cells and specific macrophages drive atherosclerosis progression by promoting lipid accumulation. Targeting this crosstalk may offer new therapeutic strategies for cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cellular Biology
Background:
- Atherosclerosis (AS) is a leading cause of mortality globally, driven by complex inflammatory processes within blood vessels.
- Understanding the cellular heterogeneity and intercellular communication in the atherosclerotic microenvironment is critical for developing effective treatments.
Purpose of the Study:
- To investigate the regulatory roles of distinct cell populations in AS pathogenesis.
- To elucidate the intercellular communication networks between vascular smooth muscle cell (VSMC)-derived foam cells and macrophages.
- To identify potential therapeutic targets for AS.
Main Methods:
- Single-cell RNA sequencing to profile cell populations in AS plaques.
- CellChat and correlation analyses to map intercellular communication pathways.
- Spatial transcriptomics to visualize cell-cell interactions.
- Functional pathway analyses (GO, KEGG) and pseudotime trajectory analysis to understand cell differentiation and dynamics.
Main Results:
- Identified enrichment of SPP1+ FABP5+ macrophages in AS plaques, associated with lipid metabolism and cell migration.
- Characterized ITLN1+ foam cells derived from VSMCs, exhibiting high expression of lipid metabolism and AS progression genes.
- Demonstrated significant interactions between ITLN1+ foam cells and SPP1+ FABP5+ macrophages via MIF-(CD74+CD44) and SPP1-CD44 axes, promoting lipid accumulation.
Conclusions:
- The crosstalk between ITLN1+ foam cells and SPP1+ macrophages is a key driver of lipid accumulation and AS progression.
- Targeting this specific cell-cell interaction presents a promising therapeutic strategy for atherosclerosis.
- Further research is needed to validate these findings for developing immunotherapies against AS.
Introduction:
Cardiovascular disease (CVD) caused by atherosclerosis (AS) remains the leading cause of mortality in developed countries. Understanding cellular heterogeneity within the inflammatory microenvironment is crucial for advancing disease management strategies. This study investigates the regulatory functions of distinct cell populations in AS pathogenesis, focusing on the interaction between vascular smooth muscle cell (VSMC)-derived ITLN1+ foam cells and SPP1+ FABP5+ macrophages.
Methods:
We employed single-cell RNA sequencing to characterize cell populations within AS plaques. Correlation analyses and the CellChat package were utilized to elucidate intercellular communication networks among various cell types. The functional roles of key subsets of macrophages and VSMCs were assessed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Pseudotime trajectory analysis was conducted to explore the dynamics of VSMC differentiation. Additionally, spatial transcriptomics analysis was used to demonstrate the physical interactions between different cell subpopulations.
Results:
We identified significant infiltration of macrophage clusters in AS, with SPP1+ FABP5+ macrophages being highly enriched in AS plaques. These macrophages were associated with lipid transport, storage, and cell migration pathways. A distinct subset of ITLN1+ foam cells derived from VSMCs exhibited robust expression of foam cell markers and lipid metabolism-related genes. Pseudotime trajectory analysis indicated that ITLN1+ foam cells represent a terminal stage of VSMC differentiation, characterized by elevated expression of genes linked to lipid synthesis and AS progression. Spatial transcriptomics and CellChat analysis revealed a significant interaction between ITLN1+ foam cells and SPP1+ FABP5+ macrophages, mediated by the MIF-(CD74 + CD44) and SPP1-CD44 ligand-receptor axes.
Discussion:
Our findings underscore the critical crosstalk between ITLN1+ foam cells and SPP1+ macrophages in promoting lipid accumulation and AS progression. Targeting this cell-cell interaction may offer new therapeutic avenues for managing atherosclerosis. Further validation of these mechanisms is necessary to develop effective immunotherapeutic strategies against AS.
