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Integrating Metabolism and Immunity | EK16


Cell type-Selective Secretome Profiling In Vivo


Jan 25, 2021 12:00am ‐ Jan 25, 2021 12:00am

Description

Cell type-Selective Secretome Profiling In Vivo Secreted polypeptides are a fundamental axis of intercellular and endocrine communication. However, a global understanding of the 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 proteins from blood plasma. Our secretome dataset 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 the increased unconventional secretion of the cytosolic enzyme betaine–homocysteine S-methyltransferase (BHMT). This secretome profiling strategy enables dynamic and cell type-specific dissection of the plasma proteome and the secreted polypeptides that mediate intercellular signaling. Wei Wei1,2,5,7, Nicholas M. Riley3,5,6,7, Andrew C. Yang4, Joon T. Kim1,5, Stephanie M. Terrell1,5, Veronica L. Li1,3,5, Marta Garcia-Contreras1,5, Carolyn R. Bertozzi3,5,6, Jonathan Z. Long1,5,* 1Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 USA 2Department of Biology, Stanford University, Stanford, CA 94305 USA 3Department of Chemistry, Stanford University, Stanford, CA 94305 USA 4Department of Bioengineering, Stanford University, Stanford, CA 94305 USA 5Stanford ChEM-H, Stanford University, Stanford, CA 94305 USA 6Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305 USA 7These authors contributed equally *To whom correspondence should be addressed. Email: jzlong@stanford.edu

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