1. Specific cell subclusters of dental pulp stem cells respond to distinct pathogens through the ROS pathway.
- Author
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Xu T, Liu Y, Zhang W, Li M, Zhang L, Li X, Zhang Y, Yue L, Li S, Lin Y, Zou X, and Chen F
- Subjects
- Humans, NF-kappa B metabolism, Young Adult, Single-Cell Analysis, Signal Transduction, Cells, Cultured, Cytokines metabolism, Dental Pulp microbiology, Dental Pulp cytology, Dental Pulp immunology, Candida albicans, Stem Cells metabolism, Reactive Oxygen Species metabolism, Streptococcus mutans genetics
- Abstract
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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Xu, Liu, Zhang, Li, Zhang, Li, Zhang, Yue, Li, Lin, Zou and Chen.)
- Published
- 2024
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