Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, China.
Department of Pediatrics, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, China.
Gene. 2021 Mar 1;771:145347. doi: 10.1016/j.gene.2020.145347. Epub 2020 Dec 15.
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.
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.
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.
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.
在 MSC 预激活过程中加入 IFN-γ 和 TNF-α 可以增强其免疫命运，并诱导更有效的免疫调节。然而，MSC 的细胞异质性限制了我们对这种炎症激活的理解。
分析了人骨髓来源 MSC 在有无 IFN-γ 和 TNF-α 激活条件下的公共基因表达组学单细胞 RNA 测序（scRNA-seq）数据。基于 scRNA-seq 数据和相关标记基因，比较了未激活和激活的 MSC 的细胞周期、干性、分化潜能和免疫调节能力。
去除低质量细胞并回归核糖体基因效应后，选择反映 IFN-γ 和 TNF-α 对 MSC 影响的高质量数据进行进一步分析。尽管存在异质性，但预激活并未影响人骨髓来源 MSC 的细胞周期和干性。成骨潜能降低，成软骨潜能增加，而脂肪形成潜能在激活的 MSC 中保持稳定。激活的 MSC 还表现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。
综上所述，我们的研究以单细胞分辨率显示了人骨髓来源未激活和激活的 MSC 关于细胞周期、干性、分化潜能和免疫调节能力的表达谱，这可能有助于全面理解人骨髓来源 MSC 的炎症激活及其进一步的临床应用。
