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解析人类间充质基质细胞中转录变化及其对免疫调节功能的影响。

Deconstructing transcriptional variations and their effects on immunomodulatory function among human mesenchymal stromal cells.

机构信息

BGI-Shenzhen, Jinsha Road, Dapeng New District, Shenzhen, 518083, China.

BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China.

出版信息

Stem Cell Res Ther. 2021 Jan 9;12(1):53. doi: 10.1186/s13287-020-02121-8.

DOI:10.1186/s13287-020-02121-8
PMID:33422149
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7796611/
Abstract

BACKGROUND

Mesenchymal stromal cell (MSC)-based therapies are being actively investigated in various inflammatory disorders. However, functional variability among MSCs cultured in vitro will lead to distinct therapeutic efficacies. Until now, the mechanisms behind immunomodulatory functional variability in MSCs are still unclear.

METHODS

We systemically investigated transcriptomic variations among MSC samples derived from multiple tissues to reveal their effects on immunomodulatory functions of MSCs. We then analyzed transcriptomic changes of MSCs licensed with INFγ to identify potential molecular mechanisms that result in distinct MSC samples with different immunomodulatory potency.

RESULTS

MSCs were clustered into distinct groups showing different functional enrichment according to transcriptomic patterns. Differential expression analysis indicated that different groups of MSCs deploy common regulation networks in response to inflammatory stimulation, while expression variation of genes in the networks could lead to different immunosuppressive capability. These different responsive genes also showed high expression variability among unlicensed MSC samples. Finally, a gene panel was derived from these different responsive genes and was able to regroup unlicensed MSCs with different immunosuppressive potencies.

CONCLUSION

This study revealed genes with expression variation that contribute to immunomodulatory functional variability of MSCs and provided us a strategy to identify candidate markers for functional variability assessment of MSCs.

摘要

背景

间充质基质细胞（MSC）为基础的治疗方法正在各种炎症性疾病中得到积极研究。然而，体外培养的 MSC 之间的功能变异性会导致不同的治疗效果。到目前为止，MSC 免疫调节功能变异性背后的机制仍不清楚。

方法

我们系统地研究了来自多种组织的 MSC 样本中的转录组变化，以揭示它们对 MSC 免疫调节功能的影响。然后，我们分析了经 INFγ 许可的 MSC 的转录组变化，以确定导致具有不同免疫调节效力的不同 MSC 样本的潜在分子机制。

结果

根据转录组模式，MSC 被聚类为不同的组，显示出不同的功能富集。差异表达分析表明，不同组的 MSC 在炎症刺激下使用共同的调节网络，而网络中基因的表达变化可能导致不同的免疫抑制能力。这些不同的响应基因在未经许可的 MSC 样本中也表现出高表达变异性。最后，从这些不同的响应基因中得出了一个基因面板，并能够对具有不同免疫抑制潜力的未经许可的 MSC 进行重新分组。

结论

本研究揭示了导致 MSC 免疫调节功能变异性的具有表达变化的基因，并为我们提供了一种识别候选标志物以评估 MSC 功能变异性的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/5c25c508d0fb/13287_2020_2121_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/4a6f20c915e7/13287_2020_2121_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/6fd99f0d69d9/13287_2020_2121_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/2f39629941f0/13287_2020_2121_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/a2c8f07d32a5/13287_2020_2121_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/2952a86dc5a4/13287_2020_2121_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/5c25c508d0fb/13287_2020_2121_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/4a6f20c915e7/13287_2020_2121_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/6fd99f0d69d9/13287_2020_2121_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/2f39629941f0/13287_2020_2121_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/a2c8f07d32a5/13287_2020_2121_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/2952a86dc5a4/13287_2020_2121_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0cfa/7796611/5c25c508d0fb/13287_2020_2121_Fig6_HTML.jpg

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