Mao Hui-Min, Guo Wan-Liang, Shi San-Li
Department of Radiology, Children'S Hospital of Soochow University, Suzhou, 215025, China.
Department of Radiology, The 8th Hospital of Xi'an, Xi'an, China.
Pediatr Surg Int. 2025 Mar 21;41(1):98. doi: 10.1007/s00383-025-05997-w.
The etiology and pathogenesis of pancreaticobiliary maljunction (PBM) remain unclear, thus a comprehensive investigation of cellular diversity and microenvironmental differences is pivotal to elucidate the mechanisms driving PBM.
We performed single-cell RNA sequencing on bile duct tissues from six patients, including three with PBM and three without (non-PBM). Pathway enrichment, transcription factor analysis, and cell-cell communication were analyzed to explore cellular interactions and functional states.
A total of 90,996 single cells and 11 distinct cell lineages were identified, revealing significant differences in cellular composition between the two groups. PBM group was characterized by a higher proportion of endothelial cells and fibroblasts, while B and T cells were less abundant. Three subtypes of fibroblasts, antigen-presenting, inflammatory, and myofibroblastic cancer-associated fibroblasts, with the myofibroblast subtype being predominant in PBM. We found heightened activity of the WNT and TWEAK signaling pathways in PBM, as well as increased ligand-receptor interactions between fibroblasts and other cell types, including epithelial and endothelial cells.
Fibroblasts play a central role in driving fibrosis and tissue remodeling in PBM through specific signaling pathways. These insights provide a foundation for future therapeutic strategies aimed at modulating fibroblast activity to prevent or mitigate fibrosis in PBM.
胰胆管合流异常（PBM）的病因和发病机制尚不清楚，因此全面研究细胞多样性和微环境差异对于阐明驱动PBM的机制至关重要。
我们对6例患者的胆管组织进行了单细胞RNA测序，其中3例患有PBM，3例未患（非PBM）。通过通路富集、转录因子分析和细胞间通讯分析来探索细胞间相互作用和功能状态。
共鉴定出90,996个单细胞和11个不同的细胞谱系，揭示了两组之间细胞组成的显著差异。PBM组的特征是内皮细胞和成纤维细胞比例较高，而B细胞和T细胞较少。成纤维细胞有三种亚型，即抗原呈递型、炎症型和成肌纤维细胞癌相关型，其中成肌纤维细胞亚型在PBM中占主导地位。我们发现PBM中WNT和TWEAK信号通路的活性增强，以及成纤维细胞与其他细胞类型（包括上皮细胞和内皮细胞）之间的配体-受体相互作用增加。
成纤维细胞通过特定的信号通路在驱动PBM的纤维化和组织重塑中起核心作用。这些见解为未来旨在调节成纤维细胞活性以预防或减轻PBM纤维化的治疗策略奠定了基础。
