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

Salivary proteins facilitate food perception and digestion, maintain the integrity of the mineralized tooth and oral epithelial surfaces, and shield the oro-digestive tract from environmental hazards and invading pathogens. Saliva, as one of the easiest to collect body fluids, also serves in diagnostic applications, with its proteins providing a window to body health. However, despite the availability of the human saliva proteome, the origins of individual proteins remain unclear. To bridge this gap, we analyzed the transcriptomes of 27 tissue samples derived from the three major types of human adult and fetal salivary glands and integrated these data with the saliva proteome and the proteomes and transcriptomes of 28+ other human organs, with tissue expression confirmed by 3D microscopy. Using these tools, we have linked saliva proteins to their source for the first time, an outcome with significant implications for basic research and diagnostic applications. Furthermore, our study represents the first comparative transcriptomic analysis of human adult and fetal exocrine organs, providing evidence that functional specialization occurs late in salivary gland development, and is driven mainly by the transcription of genes encoding secreted saliva proteins. Moreover, we found that dosage of abundant saliva proteins secreted by the salivary glands is primarily regulated at the transcriptional level, and that secreted proteins can be synthesized by distinct subsets of serous acinar cells, revealing hitherto unrecognized heterogeneity in the acinar cell lineage. Our results reveal the functional underpinnings of these secretory organs, paving the way for future investigations into saliva biology and pathology.

Keywords: Biomarker, systems biology, glandular development, proteome, transcriptome, single cell, gene regulation, tissue specific expression

Suggested Citation: Suggested Citation

Saitou, Marie and Gaylord, Eliza and Xu, Duo (Erica) and Neznanova, Lubov and Nathan, Sara and Grawe, Anissa and Chang, Jolie and Ryan, William and Ruhl, Stefan and Knox, Sarah M. and Gokcumen, Omer, Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva. Available at SSRN: https://ssrn.com/abstract=3565016 or http://dx.doi.org/10.2139/ssrn.3565016

This version of the paper has not been formally peer reviewed.