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

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 th...

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Main Authors: Dan Liang, Wei Xu, Yifan Wu, Qicheng Ye, Wanlin Xu, Hao Lu
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Journal of Dental Sciences
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Online Access:http://www.sciencedirect.com/science/article/pii/S1991790225000479
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author Dan Liang
Wei Xu
Yifan Wu
Qicheng Ye
Wanlin Xu
Hao Lu
author_facet Dan Liang
Wei Xu
Yifan Wu
Qicheng Ye
Wanlin Xu
Hao Lu
author_sort Dan Liang
collection DOAJ
description 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.
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spelling doaj-art-4fe3a791b34f47a0b07679b977eb6fe22025-06-26T09:52:17ZengElsevierJournal of Dental Sciences1991-79022025-07-0120314061414Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosisDan Liang0Wei Xu1Yifan Wu2Qicheng Ye3Wanlin Xu4Hao Lu5Department of Stomatology, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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; Corresponding author. Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Huangpu District, Shanghai 200011, 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; Corresponding author. Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, No.639, Zhizaoju Road, Huangpu District, Shanghai 200011, China.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.http://www.sciencedirect.com/science/article/pii/S1991790225000479Endothelial cellSalivary gland fibrosisSingle-cell transcriptomics
spellingShingle Dan Liang
Wei Xu
Yifan Wu
Qicheng Ye
Wanlin Xu
Hao Lu
Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
Journal of Dental Sciences
Endothelial cell
Salivary gland fibrosis
Single-cell transcriptomics
title Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
title_full Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
title_fullStr Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
title_full_unstemmed Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
title_short Single-cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
title_sort single cell genomics reveals transcriptional heterogeneity and cellular crosstalk in salivary gland fibrosis
topic Endothelial cell
Salivary gland fibrosis
Single-cell transcriptomics
url http://www.sciencedirect.com/science/article/pii/S1991790225000479
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AT yifanwu singlecellgenomicsrevealstranscriptionalheterogeneityandcellularcrosstalkinsalivaryglandfibrosis
AT qichengye singlecellgenomicsrevealstranscriptionalheterogeneityandcellularcrosstalkinsalivaryglandfibrosis
AT wanlinxu singlecellgenomicsrevealstranscriptionalheterogeneityandcellularcrosstalkinsalivaryglandfibrosis
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