ZBTB7B is a Master Regulator of Salivary Acinar Cell Function

ZBTB7B is the most connected transcription factor regulator in human salivary glands, inferred from RNA-seq and ATAC-seq chromatin footprints, and acts through salivary-specific enhancers enriched for its motifs that correlate with expression of genes including AQP5. In Zbtb7b knockout mice, single-cell RNA-seq and spatial transcriptomics show reduced salivary flow, shifted acinar cell proportions, and a neonate-like acinar population losing canonical secreted proteins while gaining MHC class I expression, despite preserved gland architecture. The work positions Zbtb7b as a master regulator that stabilizes adult acinar identity rather than maintaining gland structure.