Arg1 and Tgfb1 Identify a Partially Shared Macrophage Polarization Program in Postinfarction Cardiac Repair: A...

Area of Science:

• Immunology
• Cardiovascular Biology
• Oncology

Background:

• Postinfarction cardiac repair involves macrophages polarizing from M1 to M2 states.
• These macrophages regulate inflammation, angiogenesis, and fibrosis in the heart.
• Tumor-associated macrophages (TAMs) in breast cancer share features with M2 cardiac macrophages.

Purpose of the Study:

• To compare macrophage polarization programs in cardiac repair and breast cancer.
• To identify shared molecular mechanisms between reparative cardiac macrophages and TAMs.
• To explore potential therapeutic targets based on conserved immune programs.

Main Methods:

• Single-cell RNA sequencing of murine cardiac macrophages and human breast cancer tissues.
• Bioinformatic analyses including dimensionality reduction, clustering, and trajectory reconstruction.
• Cross-dataset correlation analysis to compare gene expression patterns between species and conditions.

Main Results:

• Macrophage polarization trajectories with M1/M2 bifurcation were identified in both datasets.
• A 7-gene coexpression module (Spp1, Mif, Tgfb1, Arg1, Il10, Tnf, Mrc1) was conserved between cardiac and breast cancer macrophages (Pearson's r = 0.72).
• Shared ligand-receptor pairs (MIF-ACKR3, SPP1-CD44, TGFB1-TGFBR2) were identified, mediating communication in both microenvironments.

Conclusions:

• Macrophage polarization programs show partial conservation between postinfarction cardiac repair and breast cancer.
• The identified 7-gene module and signaling axes offer potential therapeutic targets.
• Context-dependent differences highlight the need for further functional studies in paired models.