Decoding meningioma heterogeneity and neoplastic cell-macrophage interaction through single-cell transcriptome...

Area of Science:

• Oncology
• Genomics
• Immunology

Background:

• Meningioma, a common primary brain tumor, exhibits diverse pathological types.
• Understanding cellular heterogeneity and microenvironment interactions is crucial for meningioma research.

Purpose of the Study:

• To investigate the biological mechanisms and cellular interplay in distinct meningioma subtypes at the single-cell level.
• To identify key signaling pathways and cellular interactions driving meningioma progression.

Main Methods:

• Single-cell RNA sequencing on patient-derived meningioma samples and public datasets.
• Cellular clustering, pseudotime analysis, weighted gene co-expression network analysis, and gene regulatory network construction.
• Cell-cell communication analysis and immunofluorescence validation of key interactions.

Main Results:

• Meningioma neoplastic cells display significant inter-sample heterogeneity and diverse functions, including metabolic regulation.
• A small proliferative neoplastic cell subpopulation (N5 cluster) was identified, expressing MKI67 and TOP2A.
• Macrophages exhibited distinct pro-tumorigenic and anti-tumorigenic trajectories, with MIF-CD74 identified as a critical interaction pathway, notably involving the N5 cluster.

Conclusions:

• Meningioma neoplastic cell diversity contributes to tumor heterogeneity and varied functions.
• Proliferative neoplastic cells may educate tumor-associated macrophages via the MIF-CD74 pathway, promoting tumorigenesis.
• This study provides novel insights into meningioma pathogenesis and potential therapeutic strategies.