TY - JOUR T1 - Cell type-selective secretome profiling in vivo JF - bioRxiv DO - 10.1101/2020.09.18.303909 SP - 2020.09.18.303909 AU - Wei Wei AU - Nicholas M. Riley AU - Andrew C. Yang AU - Joon T. Kim AU - Stephanie M. Terrell AU - Veronica L. Li AU - Marta Garcia-Contreras AU - Carolyn R. Bertozzi AU - Jonathan Z. Long Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/09/20/2020.09.18.303909.abstract N2 - Secreted polypeptides are a fundamental biochemical axis of intercellular and endocrine communication. However, a global understanding of composition and dynamics of cellular secretomes in intact mammalian organisms has been lacking. Here, we introduce a proximity biotinylation strategy that enables labeling, detection, and enrichment of secreted polypeptides in a cell type-selective manner in mice. We generate a proteomic atlas of hepatocyte, myocyte, pericyte, and myeloid cell secretomes by direct purification of biotinylated secreted polypeptides from blood. Our secretome atlas validates known cell type-protein pairs, reveals secreted polypeptides that distinguish between cell types, and identifies new cellular sources for classical plasma proteins. Lastly, we uncover a dynamic and previously undescribed nutrient-dependent reprogramming of the hepatocyte secretome characterized by increased unconventional secretion of the cytosolic enzyme BHMT. This secretome profiling strategy enables dynamic and cell-type dissection of the plasma proteome and the secreted polypeptides that mediate intercellular signaling.Competing Interest StatementThe authors have declared no competing interest. ER -