Single-cell RNA-Seq reveals the heterogeneity of fibroblasts within the tympanojugular paraganglioma microenvironment
Shengming Wang,
Boya Zhang,
Zihan Lou,
Yibing Hu,
Jian Wang,
Jingjing Wang,
Zhengnong Chen,
Shankai Yin
Affiliations
Shengming Wang
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Boya Zhang
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Zihan Lou
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yibing Hu
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Jian Wang
School of Communication Sciences and Disorders, Dalhousie University, Halifax, NS, Canada
Jingjing Wang
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author. Otolaryngology Institute of Shanghai Jiao Tong University, Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 YiShan Road, XuHui District, Shanghai City, China.
Zhengnong Chen
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author. Otolaryngology Institute of Shanghai Jiao Tong University, Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 600 YiShan Road, XuHui District, Shanghai City, China.
Shankai Yin
Otolaryngology Institute of Shanghai Jiao Tong University, China; Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Tympanojugular paragangliomas (TJP) originate from the parasympathetic ganglia in the lateral base of the skull. Although the cellular composition and oncogenic mechanisms of paragangliomas have been evaluated, a comprehensive transcriptomic atlas specific to TJP remains to be established to facilitate further investigations. In this study, single-cell RNA sequencing and whole-exome sequencing were conducted on six surgically excised TJP samples to determine their cellular composition and intratumoral heterogeneity. Fibroblasts were sub-classified into two distinct groups: myofibroblasts and fibroblasts associated with bone remodeling. Additionally, an elaborate regulatory and cell–cell communication network was determined, highlighting the multifaceted role of fibroblasts, which varies depending on expression transitions. The Kit receptor (KIT) signaling pathway mediated interactions between fibroblasts and mast cells, whereas robust connections with endothelial and Schwann cell-like cells were facilitated through the platelet-derived growth factor signaling pathway. These findings establish a foundation for studying the mechanisms underlying protumor angiogenesis and the specific contributions of fibroblasts within the TJP microenvironment. IL6 signaling pathway of fibroblasts interacting with macrophages and endothelial cells may be involved in tumor regrowth. These results enhance our understanding of fibroblast functionality and provide a resource for future therapeutic targeting of TJP.
