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

BACKGROUND/PURPOSESalivary 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 METHODSWe 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.

RESULTSThe 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.

CONCLUSIONThis 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.