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Cell type-selective secretome profiling in vivo

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 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 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.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Pericyte, Hepatocyte, Liver, Cell Culture, Rhabdomyocyte, Blood

SUBMITTER: Nicholas Riley

LAB HEAD: Jonathan Z. Long

PROVIDER: PXD021602 | Pride | 2020-12-07

REPOSITORIES: Pride

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			Action	DRS
	AAV_FLEx_Albumin_cre1.raw	Raw
	AAV_FLEx_Albumin_cre2.raw	Raw
	AAV_FLEx_Albumin_cre3.raw	Raw
	AAV_FLEx_LysM-creERT2_1.raw	Raw
	AAV_FLEx_LysM-creERT2_2.raw	Raw

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Cell type-selective secretome profiling in vivo

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