Heterogeneity in Dental Tissue-Derived MSCs Revealed by Single-Cell RNA-seq.

IF 5.7 1区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
C Behm,O Miłek,K Schwarz,A Kovar,S Derdak,X Rausch-Fan,A Moritz,O Andrukhov
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引用次数: 0

Abstract

Mesenchymal stromal cells (MSCs) are multipotent, progenitor cells that reside in tissues across the human body, including the periodontal ligament (PDL) and gingiva. They are a promising therapeutic tool for various degenerative and inflammatory diseases. However, different heterogeneity levels caused by tissue-to-tissue and donor-to-donor variability, and even intercellular differences within a given MSCs population, restrict their therapeutic potential. There are considerable efforts to decipher these heterogeneity levels using different "omics" approaches, including single-cell transcriptomics. Previous studies applied this approach to compare MSCs isolated from various tissues of different individuals, but distinguishing between donor-to-donor and tissue-to-tissue variability is still challenging. In this study, MSCs were isolated from the PDL and gingiva of 5 periodontally healthy individuals and cultured in vitro. A total of 3,844 transcriptomes were generated using single-cell mRNA sequencing. Clustering across the 2 different tissues per donor identified PDL- and gingiva-specific and tissue-spanning MSCs subpopulations with unique upregulated gene sets. Gene/pathway enrichment and protein-protein interaction (PPI) network analysis revealed differences restricted to several cellular processes between tissue-specific subpopulations, indicating a limited tissue-of-origin variability in MSCs. Gene expression, pathway enrichment, and PPI network analysis across all donors' PDL- or gingiva-specific subpopulations showed significant but limited donor-to-donor differences. In conclusion, this study demonstrates tissue- and donor-specific variabilities in the transcriptome level of PDL- and gingiva-derived MSCs, which seem restricted to specific cellular processes. Identifying tissue-specific and tissue-spanning subpopulations highlights the intercellular differences in dental tissue-derived MSCs. It could be reasonable to control MSCs at a single-cell level to ensure their properties before transplantation.
单细胞 RNA 序列分析揭示牙组织来源间充质干细胞的异质性
间充质基质细胞(MSCs)是一种多能的祖细胞,存在于包括牙周韧带(PDL)和牙龈在内的人体各组织中。它们是治疗各种退行性和炎症性疾病的一种很有前景的工具。然而,由于组织与组织之间、供体与供体之间的差异,甚至特定间充质干细胞群体内部细胞间的差异,导致异质性水平不同,从而限制了它们的治疗潜力。目前人们正努力利用不同的 "omics "方法(包括单细胞转录组学)来破译这些异质性水平。以前的研究采用这种方法对从不同个体的不同组织中分离出来的间充质干细胞进行比较,但区分供体与供体之间以及组织与组织之间的变异性仍具有挑战性。本研究从5名牙周健康者的PDL和牙龈中分离出间叶干细胞并进行体外培养。通过单细胞 mRNA 测序共生成了 3,844 个转录组。通过对每个供体的 2 种不同组织进行聚类,确定了具有独特上调基因组的 PDL 和牙龈特异性及跨组织间充质干细胞亚群。基因/通路富集和蛋白-蛋白相互作用(PPI)网络分析显示,组织特异性亚群之间的差异仅限于几个细胞过程,这表明间充质干细胞的原发组织变异性有限。对所有供体的PDL或龈特异性亚群进行的基因表达、通路富集和PPI网络分析显示,供体与供体之间存在显著但有限的差异。总之,本研究证明了PDL和牙龈来源间充质干细胞转录组水平的组织特异性和供体特异性差异,这些差异似乎仅限于特定的细胞过程。识别组织特异性和组织跨度亚群突出了牙组织间充质干细胞的细胞间差异。在移植前从单细胞水平控制间充质干细胞以确保其特性是合理的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Dental Research
Journal of Dental Research 医学-牙科与口腔外科
CiteScore
15.30
自引率
3.90%
发文量
155
审稿时长
3-8 weeks
期刊介绍: The Journal of Dental Research (JDR) is a peer-reviewed scientific journal committed to sharing new knowledge and information on all sciences related to dentistry and the oral cavity, covering health and disease. With monthly publications, JDR ensures timely communication of the latest research to the oral and dental community.
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