Competence Center for Periodontal Research, University Clinic of Dentistry, Medical University of Vienna, Austria.
Core Facilities, Medical University of Vienna, Vienna, Austria.
J Dent Res. 2024 Oct;103(11):1141-1152. doi: 10.1177/00220345241271997. Epub 2024 Sep 26.
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.
间充质基质细胞 (MSCs) 是多能祖细胞，存在于人体的各种组织中，包括牙周韧带 (PDL) 和牙龈。它们是治疗各种退行性和炎症性疾病的有前途的治疗工具。然而，由于组织间和供体间的变异性，甚至在给定的 MSCs 群体内的细胞间差异，导致不同的异质性水平，限制了它们的治疗潜力。人们做出了相当大的努力，使用不同的“组学”方法来解析这些异质性水平，包括单细胞转录组学。以前的研究应用这种方法比较了来自不同个体不同组织的 MSCs，但区分供体间和组织间的变异性仍然具有挑战性。在这项研究中，从 5 名牙周健康个体的牙周韧带和牙龈中分离出 MSCs，并在体外培养。使用单细胞 mRNA 测序共生成了 3844 个转录组。对每个供体的 2 种不同组织进行聚类，确定了 PDL 和牙龈特异性以及跨越组织的 MSCs 亚群，这些亚群具有独特上调的基因集。基因/途径富集和蛋白质-蛋白质相互作用 (PPI) 网络分析显示，组织特异性亚群之间仅存在几个细胞过程的差异，表明 MSCs 的组织来源变异性有限。对所有供体的 PDL 或牙龈特异性亚群的基因表达、途径富集和 PPI 网络分析表明，供体间存在显著但有限的差异。总之，这项研究表明，PDL 和牙龈来源的 MSCs 在转录组水平上存在组织和供体特异性变异性，这些变异性似乎仅限于特定的细胞过程。鉴定组织特异性和跨越组织的亚群突出了牙齿组织来源的 MSCs 中的细胞间差异。在移植前控制 MSCs 到单细胞水平以确保其特性可能是合理的。
