09/16/2026
Deep scRNA-seq missed it. Single-cell proteomics found it.
We profiled thousands of single PBMCs โ proteomes and transcriptomes side by side โ and uncovered functional coordination undetectable in the deepest scRNA-seq we could perform.
PBMCs are widely studied cells in single-cell biology. Millions of PBMCs have been analyzed by scRNA-seq. Have we seen it all ?
Interestingly, single-cell mass spectrometry (plexDIA) quantified more protein-coding gene products per cell than the RNA measurements, with substantially higher data completeness. The consistency and quantification accuracy makes it possible to ask a challenging question:
๐๐จ๐ฐ ๐๐จ ๐ ๐๐ง๐ ๐ฉ๐ซ๐จ๐๐ฎ๐๐ญ๐ฌ ๐ฏ๐๐ซ๐ฒ ๐ญ๐จ๐ ๐๐ญ๐ก๐๐ซ ๐๐ซ๐จ๐ฆ ๐๐๐ฅ๐ฅ ๐ญ๐จ ๐๐๐ฅ๐ฅ ๐ฐ๐ข๐ญ๐ก๐ข๐ง ๐ญ๐ก๐ ๐ฌ๐๐ฆ๐ ๐๐๐ฅ๐ฅ ๐ญ๐ฒ๐ฉ๐ ?
The protein measurements revealed cell-type-specific proteome architecture -- shaped in part by protein stability, and complex coordination -- that was undetectable in our mRNA data. Specifically, protein covariation within a cell type suggests cell-type-specific protein-protein interactions and functional rewiring of biological pathways independent of abundance differences.
Some examples:
1๏ธโฃ Arp2/3 complex shows distinct protein-level coordination across immune cell types, while this organization is largely absent from the corresponding mRNA data.
2๏ธโฃ Protein covariation reveal an axis of translational states in B cells that tracks inversely with the abundance cytokine GDF6, suggesting reciprocal regulation of protein synthesis and GDF6 priming.
The broader message is simple:
๐ท Single-cell proteomics opens a new window to a layer of functional coordination that had remained remained undetected.
We are excited to open this window wider and investigate deeper !
https://www.biorxiv.org/content/10.64898/2026.09.11.751068v1.full
