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ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Oral Microbes and Host
Volume 14 - 2024 |
doi: 10.3389/fcimb.2024.1452124
Specific cell subclusters of dental pulp stem cells respond to distinct pathogens through the ROS pathway
Provisionally accepted- 1 Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
- 2 Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
- 3 Department of Implantology, Peking University School and Hospital of Stomatology, Beijing, China
- 4 Center of Stomatology, Peking University Hospital, Beijing, China
Introduction: Microbial pathogens invade various human organs, including the oral cavity. Candida albicans (C.a) and Streptococcus mutans (S.m) served respectively as representative oral pathogenic fungi and bacteria to stimulate dental pulp stem cells (DPSCs) and to screen the DPSC subcluster that specifically responded to fungal infection. Methods: DPSCs were obtained from the impacted third molars of six healthy subjects. Then, cells were mixed and divided into three samples, two of which were stimulated with C.a and S.m, respectively; the third sample was exposed to cell medium only (Ctrl). Single-cell mRNA sequencing analysis of treated DPSCs was performed. Results: DPSCs were composed of four major clusters of which one, DPSC.7, exhibited unique changes compared to those of other subclusters. The DPSC.7 cell percentage of the C.a sample was twice those of the Ctrl and S.m samples. DPSC.7 cells expressed genes associated with the response to reactive oxygen species (ROS) response. DPSC.7 subgroup cells established characteristic aggregation under the stimulation of different pathogens in UMAP. The MAPK/ERK1/2 and NF-κB pathways were up-regulated, DUSP1/5/6 expressions were suppressed, FOS synthesis was activated, the immune-related pathway was induced, and the levels of cytokines, including IL-6 and CCL2, were up-regulated in DPSC.7 cells when stimulated with C.a. Conclusions: Our study analyzed the cellular and molecular properties of DPSCs infected by oral fungi and bacteria with single-cell RNA sequencing. A subcluster of DPSCs responded specifically to infections with different pathogens, activating the MAPK and NF-κB pathways to induce immune responses via the ROS pathway. This suggests novel treatment strategies for fungal infections.
Keywords: dental pulp stem cells, Candida albicans, MAPK/ERK1/2, Fos, immune response
Received: 20 Jun 2024; Accepted: 12 Aug 2024.
Copyright: © 2024 Xu, Liu, Zhang, Li, Zhang, Li, Zhang, Yue, Li, Lin, Zou and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Liqi Zhang, Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
Xueying Li, Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
Lin Yue, Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
Sha Li, Department of Implantology, Peking University School and Hospital of Stomatology, Beijing, China
Ye Lin, Department of Implantology, Peking University School and Hospital of Stomatology, Beijing, China
Xiaoying Zou, Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
Feng Chen, Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China
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