Cell type-selective secretome profiling in vivo.

Autor: Wei W; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Biology, Stanford University, Stanford, CA, USA.; Stanford ChEM-H, Stanford University, Stanford, CA, USA., Riley NM; Stanford ChEM-H, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA., Yang AC; Department of Bioengineering, Stanford University, Stanford, CA, USA., Kim JT; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford ChEM-H, Stanford University, Stanford, CA, USA., Terrell SM; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford ChEM-H, Stanford University, Stanford, CA, USA., Li VL; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford ChEM-H, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA., Garcia-Contreras M; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Stanford ChEM-H, Stanford University, Stanford, CA, USA., Bertozzi CR; Stanford ChEM-H, Stanford University, Stanford, CA, USA.; Department of Chemistry, Stanford University, Stanford, CA, USA.; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA., Long JZ; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. jzlong@stanford.edu.; Stanford ChEM-H, Stanford University, Stanford, CA, USA. jzlong@stanford.edu.
Jazyk: angličtina
Zdroj: Nature chemical biology [Nat Chem Biol] 2021 Mar; Vol. 17 (3), pp. 326-334. Date of Electronic Publication: 2020 Nov 16.
DOI: 10.1038/s41589-020-00698-y
Abstrakt: 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.
Databáze: MEDLINE
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