NGFR-marked basal duct progenitors drive ductal-acinar regeneration in injured salivary glands

ABSTRACT: Severe salivary gland injury causes long-term structural and functional impairment, yet the epithelial populations associated with repair remain incompletely defined. Here, we identify NGFR as a surface marker of a basal duct-associated epithelial population with organoid-forming capacity in the human salivary gland and show that Ngfr marks a conserved injury-responsive epithelial population in the mouse salivary gland. Single-cell RNA sequencing of human salivary gland tissue revealed that NGFR was enriched in a restricted basal duct subpopulation distinct from differentiated epithelial and myoepithelial compartments. NGFR-positive cells exhibited a progenitor-like transcriptional profile and were enriched at early pseudotime positions in inferred ductal-acinar differentiation trajectories. Functionally, NGFR-positive cells isolated from human tissue and organoids showed enhanced organoid-forming capacity, and NGFR-enriched organoids engrafted into injured mouse salivary glands. In mouse salivary glands, Ngfr marked a rare epithelial population whose isolated Ngfr-positive fraction showed enriched organoid-forming activity and was detected in injury-associated ductal regions after duct ligation and local inflammatory injury. Lineage tracing using Ngfr-CreERT2; Rosa26-tdTomato mice further showed that Ngfr-lineage cells contribute to ductal and acinar epithelial compartments during post-injury regeneration. Together, these findings define NGFR in human and Ngfr in mouse as conserved markers of an injury-responsive basal duct epithelial population that can be prospectively isolated and contributes to ductal and acinar epithelial compartments during post-injury salivary gland regeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE330533 | GEO | 2026/05/15

REPOSITORIES: GEO