Single-cell proteomics reveals cell-type-specific functional coordination in PBMCs
- 1Northeastern University and Parallel Squared Technology Institute
Abstract
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 (Smart-seq3xpress) to analyze the proteomes and transcriptomes of thousands of single peripheral blood mononuclear cells (PBMCs). plexDIA quantified more protein-coding gene products per cell with higher data completeness while Smart-seq3xpress quantified more gene products across all cells. 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 previously characterized abundance differences. Covariation analysis within cell types resolves a B cell-specific axis of translational states inversely covarying with GDF6 cytokine abundance. Our framework captures cell-type-specific functional coordination representing a distinct information layer accessible via single-cell proteomics.
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BibTeX
@misc{koury2026singlecell,
title = {{Single-cell proteomics reveals cell-type-specific functional coordination in PBMCs}},
author = {L. Koury and A. Leduc and S. Khan and M. Hagemann-Jensen and J. Michaelsson and J. E. Mold and N. Slavov},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.11.751068},
url = {https://www.biorxiv.org/content/10.64898/2026.09.11.751068v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Single-cell proteomics reveals cell-type-specific functional coordination in PBMCs
AU - L. Koury
AU - A. Leduc
AU - S. Khan
AU - M. Hagemann-Jensen
AU - J. Michaelsson
AU - J. E. Mold
AU - N. Slavov
PY - 2026
DA - 2026/09/11
PB - bioRxiv
DO - 10.64898/2026.09.11.751068
UR - https://www.biorxiv.org/content/10.64898/2026.09.11.751068v1
AB - 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 (Smart-seq3xpress) to analyze the proteomes and transcriptomes of thousands of single peripheral blood mononuclear cells (PBMCs). plexDIA quantified more protein-coding gene products per cell with higher data completeness while Smart-seq3xpress quantified more gene products across all cells. 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 previously characterized abundance differences. Covariation analysis within cell types resolves a B cell-specific axis of translational states inversely covarying with GDF6 cytokine abundance. Our framework captures cell-type-specific functional coordination representing a distinct information layer accessible via single-cell proteomics.
ER -