Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva
Marie Saitou,
Eliza A. Gaylord,
Erica Xu,
Alison J. May,
Lubov Neznanova,
Sara Nathan,
Anissa Grawe,
Jolie Chang,
William Ryan,
Stefan Ruhl,
Sarah M. Knox,
Omer Gokcumen
Affiliations
Marie Saitou
Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, U.S.A; Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Viken, Norway
Eliza A. Gaylord
Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A
Erica Xu
Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A
Alison J. May
Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A
Lubov Neznanova
Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A
Sara Nathan
Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A
Anissa Grawe
Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A
Jolie Chang
Department of Otolaryngology, School of Medicine, University of California, San Francisco, CA, U.S.A
William Ryan
Department of Otolaryngology, School of Medicine, University of California, San Francisco, CA, U.S.A
Stefan Ruhl
Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A; Corresponding author
Sarah M. Knox
Program in Craniofacial Biology, Department of Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA, U.S.A; Corresponding author
Omer Gokcumen
Department of Biological Sciences, University at Buffalo, The State University of New York, Buffalo, NY, U.S.A; Corresponding author
Summary: 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.
