Cell Differentiation of DPSCs Infected With Different Periodontal Pathogens

ABSTRACT Aim The aim of the present study was to investigate the effects of Capnocytophaga periodontitidis ( C. periodontitidis ) and Porphyromonas gingivalis ( P. gingivalis ) on dental pulp stem cells (DPSCs) subclusters. Materials and Methods DPSCs were collected from healthy donors and were infected with C. periodontitidis or P. gingivalis . High‐throughput single‐cell RNA sequencing of infected DPSCs was performed to analyze gene expression changes, focusing on differentiation, hypoxia, and cell cycle‐related pathways. Results Based on our single‐cell resolution analysis, four major DPSC clusters were identified: classical‐like, fibroblast‐like, smooth muscle‐like, and perivascular‐like. C. periodontitidis infection induced differentiation into smooth muscle‐like cells, while P. gingivalis promoted fibroblast (mineralized) lineages. P. gingivalis had a more significant effect on DPSCs differentiation. A specific subcluster responded uniquely to C. periodontitidis , with gene expression linked to B cell activation, muscle proliferation, and ROS pathways. Conclusion DPSCs showed the homogeneity and heterogeneity when infected by these two pathogens. DPSCs differentiated into smooth muscle‐related cells and mineralization‐related cells when infected by C. periodontitidis and P. gingivalis , respectively. Our results will facilitate understanding and therapeutic strategies of primary periodontal disease with secondary endodontic involvement.