Journal
NATURE CHEMICAL BIOLOGY
Volume 17, Issue 3, Pages 326-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41589-020-00698-y
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Funding
- US National Institutes of Health [DK105203, DK124265, K00CA21245403]
- Stanford Diabetes Research Center [P30DK116074]
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This study introduced a proximity biotinylation strategy to label, detect, and enrich secreted polypeptides in a cell type-selective manner in mice, resulting in a proteomic atlas of secretomes from various cell types. The research confirmed known cell type-protein pairs, identified new secreted polypeptides distinguishing between cell types, and uncovered a dynamic nutrient-dependent reprogramming of hepatocyte secretome. The strategy enables dynamic and cell type-specific dissection of the plasma proteome and intercellular signaling mediators.
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.
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