Single-cell profiles of human bone marrow-derived mesenchymal stromal cells after IFN-γ and TNF-α licensing

Background: Pre-licensing mesenchymal stromal cells (MSCs) with IFN-gamma and TNF-alpha can empower their immune fate and induce a more effective immune regulation. However, the cellular heterogeneity of MSCs limits our understanding of this inflammatory licensing. Methods: The publicly available Gene Expression Omnibus single-cell RNA sequencing (scRNA-seq) data of human bone marrow-derived MSCs with or without IFN-gamma and TNF-alpha licensing were analyzed. Based on the scRNA-seq data and related marker genes, the cell-cycle, stemness, differentiative potencies, and immunomodulate capability of unlicensed and licensed MSCs were compared. Results: After removing low-quality cells and regressing out the ribosomal gene effects, high-quality data reflecting IFN-gamma and TNF-alpha effect on MSCs were chosen for further analysis. Despite the heterogeneity, prelicensing didn't influence the cell-cycle and stemness of human bone marrow-derived MSCs. The osteogenesis potencies were decreased, the chondrogenesis potencies were increased while the adipogenesis potencies were stable in licensed MSCs. Licensed MSCs also showed more effective immunomodulate capability including expression of related chemokines, cytokines, surface molecules, and receptors. Conclusion: Collectively, our study showed the expression profiles of human bone marrow-derived unlicensed and licensed MSCs about the cell cycle, stemness, differentiative potencies, and immunomodulate capability at single-cell resolution, which may help the comprehensive understanding about the inflammatory licensing of human bone marrow-derived MSCs and their further clinical application.

Automated summary

This study compared the differences in cell cycle, stemness, differentiative potencies, and immunomodulate capability between unlicensed and licensed human bone marrow-derived MSCs using single-cell RNA sequencing data. The results showed that licensed MSCs exhibited enhanced immunomodulate capability and altered differentiation potencies compared to unlicensed MSCs.