Background

Pre-licensing mesenchymal stromal cells (MSCs) with IFN-γ and TNF-α 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-γ and TNF-α 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-γ and TNF-α effect on MSCs were chosen for further analysis. Despite the heterogeneity, pre-licensing 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.

中文翻译：

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IFN-γ和TNF-α许可后人骨髓间充质基质细胞的单细胞特征

背景

使用IFN-γ和TNF-α预先许可间充质基质细胞（MSC）可以增强其免疫力并诱导更有效的免疫调节。但是，MSCs的细胞异质性限制了我们对这种炎症许可的理解。

方法

分析了具有或不具有IFN-γ和TNF-α许可的人骨髓来源MSC的可公开获得的Gene Expression Omnibus单细胞RNA测序（scRNA-seq）数据。基于scRNA-seq数据和相关的标记基因，比较了未经许可和许可的MSC的细胞周期，干性，分化潜能和免疫调节能力。

结果

在去除劣质细胞并消灭核糖体基因效应后，选择反映IFN-γ和TNF-α对MSC效应的高质量数据进行进一步分析。尽管存在异质性，但预许可并不会影响人骨髓源性MSC的细胞周期和干性。在许可的MSC中，成骨能力降低，软骨生成能力增加，而脂肪生成能力稳定。获得许可的MSC还显示出更有效的免疫调节能力，包括相关趋化因子，细胞因子，表面分子和受体的表达。

结论

总体而言，我们的研究显示了人类骨髓来源的未经许可和许可的MSC在单细胞分辨率下的有关细胞周期，干性，分化潜能和免疫调节能力的表达概况，这可能有助于全面了解人类骨骼的炎症许可骨髓间充质干细胞及其进一步的临床应用。