Single-cell transcriptomic analysis identified resistant MDSCs and a stress-tolerant gene co-expression network as...

Area of Science:

• Immunology
• Cell Biology
• Transcriptomics

Background:

• Myeloid-derived suppressor cells (MDSCs) are a diverse group of immunosuppressive cells crucial in immune regulation.
• Identifying a universal molecular signature for MDSCs is vital for accurate classification across different tissues.

Purpose of the Study:

• To characterize heterogeneity within monocytic MDSCs (M-MDSCs) using single-cell RNA sequencing.
• To identify a common molecular signature for MDSCs, particularly under conditions of inflammation and cellular stress.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) of human MDSCs induced by GM-CSF and IL-6.
• Incorporation of cell stress via serum starvation during cytokine treatment.
• Analysis of independent bulk and single-cell transcriptomic datasets for validation.

Main Results:

• A distinct cluster of stress-resistant MDSCs (rMDSCs) was identified, characterized by a specific gene co-expression module (yellow module).
• The yellow module, enriched in stress-tolerant genes, effectively distinguished M-MDSCs from control cells (ROC AUC = 0.954).
• This rMDSC signature was found in human cancer datasets, with high expression in immunosuppressive tumor C1Q macrophages.

Conclusions:

• Inflammation and cellular stress synergistically shape M-MDSC features, emphasizing the role of cellular resilience.
• The identified stress-tolerant gene signature provides a robust marker for MDSC classification and understanding their function in cancer.