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Single-cell proteomics reveals cell-type-specific functional coordination in PBMCs

The coordination of molecular networks defines cellular functions. This is reflected in molecular covariation within a cell type, which is more subtle than the differences separating cell types and has therefore been difficult to quantify. To achieve the depth, consistency and accuracy required to resolve such covariation, we leveraged single-cell proteomics (plexDIA) and transcriptomics…

Single-cell proteomics has unveiled previously unappreciated coordination between protein networks within distinct cell types, according to a recent study. This approach, which analyzes thousands of individual peripheral blood mononuclear cells (PBMCs), revealed molecular covariation that was more nuanced than differences between cell types.

Two complementary single-cell techniques -- plexDIA for protein measurements and Smart-seq3xpress for transcriptomics -- were combined to quantify protein-coding gene products and mRNA, respectively. The proteomic data exposed a cell-type-specific proteome architecture, shaped by factors like protein stability, that was hidden in the mRNA data.

Crucially, protein covariation within a cell type suggested unique protein-protein interactions and rewiring of biological pathways, even when overall protein abundance varied. The researchers identified a specific B cell-specific axis of translational states that inversely correlated with GDF6 cytokine levels. This framework demonstrates that single-cell proteomics can provide a new layer of insight into cell-type-specific functional coordination, offering a more complete picture of cellular complexity than either protein or gene expression data alone.

Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.

Read the original at biorxiv.org →

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