Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva.

Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease. However, their precise organ origins remain unclear. Through transcriptomic analysis of major adult and fetal salivary glands and integration with the saliva proteome, the blood plasma proteome, and transcriptomes of 28+ organs, we link human saliva proteins to their source, identify salivary-gland-specific genes, and uncover fetal- and adult-specific gene repertoires. Our results also provide insights into the degree of gene retention during gland maturation and suggest that functional diversity among adult gland types is driven by specific dosage combinations of hundreds of transcriptional regulators rather than by a few gland-specific factors. Finally, we demonstrate the heterogeneity of the human acinar cell lineage. Our results pave the way for future investigations into glandular biology and pathology, as well as saliva's use as a diagnostic fluid.