单细胞基因组学揭示了唾液腺纤维化中的转录异质性和细胞间串扰。

Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis.

作者信息

Liang Dan, Xu Wei, Wu Yifan, Ye Qicheng, Xu Wanlin, Lu Hao

机构信息

Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Disease, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.

出版信息

J Dent Sci. 2025 Jul;20(3):1406-1414. doi: 10.1016/j.jds.2025.02.015. Epub 2025 Feb 25.

DOI:10.1016/j.jds.2025.02.015

PMID:40654481

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12254819/

Abstract

BACKGROUND/PURPOSE: Salivary gland fibrosis (SGF) is a prevalent condition associated with various pathological states. However, a detailed understanding of the single-cell transcriptional profiles and cell-cell communication networks in this context remains elusive. Therefore, we aimed to unveil the gene expression profiles and intercellular communication patterns in SGF.

MATERIALS AND METHODS

We established fibrosis models of the submandibular gland (SMG) and generated a detailed single-cell transcriptomic atlas to investigate cellular heterogeneity and communication patterns. Utilizing CellChat, we dissected the intercellular dialogues within these fibrotic environments.

RESULTS

The analysis distinguished fifteen distinct cellular clusters, highlighting significant heterogeneity among fibroblasts in fibrotic SMGs compared to their healthy counterparts. This heterogeneity was linked to TGF-β signaling, collagen fibril assembly, and extracellular matrix organization. CellChat analyses uncovered enhanced cell-cell interactions, notably between fibroblasts and endothelial cells (ECs) via the Gas6-Axl signaling axis. Additionally, our data indicated the activation of cell adhesion molecules and Rap1 pathways in ECs within the fibrotic SMG microenvironment.

CONCLUSION

This study offers an in-depth single-cell resolution perspective on the cellular and molecular changes in SMG fibrosis, identifying new potential therapeutic targets for this condition.

摘要

背景/目的：涎腺纤维化（SGF）是一种与多种病理状态相关的常见病症。然而，在此背景下对单细胞转录谱和细胞间通信网络的详细了解仍然难以捉摸。因此，我们旨在揭示SGF中的基因表达谱和细胞间通信模式。

材料与方法

我们建立了下颌下腺（SMG）的纤维化模型，并生成了详细的单细胞转录组图谱，以研究细胞异质性和通信模式。利用CellChat，我们剖析了这些纤维化环境中的细胞间对话。

结果

分析区分出15个不同的细胞簇，突出了纤维化SMG中的成纤维细胞与其健康对应物相比存在的显著异质性。这种异质性与TGF-β信号传导、胶原纤维组装和细胞外基质组织有关。CellChat分析发现细胞间相互作用增强，特别是成纤维细胞与内皮细胞（ECs）之间通过Gas6-Axl信号轴的相互作用。此外，我们的数据表明纤维化SMG微环境中ECs中的细胞粘附分子和Rap1途径被激活。