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bioRxiv · 10.1101/2020.09.18.303909

Cell type-selective secretome profiling in vivo

Wei, W.·Riley, N. M.·Yang, A. C.·Kim, J. T.·Terrell, S. M.·Li, V. L.·Garcia-Contreras, M.·Bertozzi, C. R.·Long, J. Z.
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Abstract

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.

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Wei, W., Riley, N. M., Yang, A. C., Kim, J. T., Terrell, S. M., Li, V. L., Garcia-Contreras, M., Bertozzi, C. R., Long, J. Z.. 2020-09-20. Cell type-selective secretome profiling in vivo. https://doi.org/10.1101/2020.09.18.303909

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