Cell type-selective secretome profiling in vivo.

Wei Wei, Nicholas M Riley, Andrew C Yang, Joon T Kim, Stephanie M Terrell, Veronica L Li, Marta Garcia-Contreras, Carolyn R Bertozzi, Jonathan Z Long

Nature chemical biology 2021 Mar

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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.

Citation

Wei Wei, Nicholas M Riley, Andrew C Yang, Joon T Kim, Stephanie M Terrell, Veronica L Li, Marta Garcia-Contreras, Carolyn R Bertozzi, Jonathan Z Long. Cell type-selective secretome profiling in vivo. Nature chemical biology. 2021 Mar;17(3):326-334