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Qi-Wen Man,1,2,* Rui-Fang Li,1,* Su-Ran Li,1 Jing Wang,1 Lin-Lin Bu,1,2 Yi Zhao,3 Bing Liu1,2 1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 2Department of Oral and Maxillofacial Head Neck Surgery, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China; 3Department of Prosthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing Liu; Yi Zhao Tel/Fax +86 87686215Email liubing9909@whu.edu.cn; Zhao_yi@whu.edu.cnPurpose: We aimed to define cell subpopulations of odontogenic keratocyst (OKC), particularly relating to angiogenesis and explored the potential regulation mechanism for angiogenesis.Materials and Methods: Single-cell RNA sequencing (scRNA-seq) analysis was investigated on 14,072 cells from 3 donors with OKC. The differential expressed genes, cell trajectory and intercellular communications were evaluated by bioinformatic analysis. Hydrostatic pressure (80 mmHg, 6h) was applied to the primary fibroblasts of OKC and the supernatant was collected for cytokines detection by cytokine antibody array. The chemokine (C-X-C motif) ligand 12 (CXCL12) and CD31 expressions were explored by immunohistochemistry in tissue microarray of OKC.Results: Five different cell types were identified in the epithelium of OKC and 3 different cell types in the OKC fibroblasts were characterized, indicating high intra-lesional heterogeneity. CXCLs were highly enriched in the subset of fibroblasts and showed close interactions with endothelial cells. Hydrostatic pressure (80mmHg) significantly increased CXCL12 secretions in OKC fibroblasts. Stromal CXCL12 expressions were closely related to CD31 expressions of tissue microarray