Single-Cell Sequencing Reveals MYOF-Enriched Monocyte/Macrophage Subcluster as a Favorable Prognostic Factor in...

Area of Science:

• Immunology
• Genomics
• Computational Biology

Background:

• Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Understanding the intricate immune cell dynamics in sepsis is crucial for developing effective treatments.

Purpose of the Study:

• To comprehensively map the immune cell landscape in sepsis using single-cell RNA sequencing.
• To identify key genes and pathways associated with sepsis survival and immune regulation.
• To explore the therapeutic potential of identified immune cell subsets and genes.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to profile immune cells in sepsis.
• Bioinformatic analyses including clustering, pathway enrichment (KEGG, GO), Gene Set Variation Analysis (GSVA), and Accessible Transcription factor knowledge-based Universal Regulatory Element (AUCell).
• In vitro (THP-1 cells) and in vivo (C57 mice) validation of gene expression and functional roles.

Main Results:

• Identification of 28 distinct immune cell clusters, categorized into nine major types, with 12 monocyte/macrophage subclusters detailed.
• Enriched pathways include oxidative phosphorylation and antigen processing; interferon pathways show varied activation.
• The gene MYOF was identified with elevated expression in sepsis survivors, demonstrating a dose-dependent response to LPS and suggesting a role in immune regulation.

Conclusions:

• Single-cell RNA sequencing provides a high-resolution view of the sepsis immune landscape.
• MYOF emerges as a significant gene associated with sepsis survival and immune response.
• Targeting MYOF+ monocyte/macrophage subsets may offer novel therapeutic strategies for sepsis.