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Mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation
Author(s) -
Levy Ezra,
Budnik Bogdan,
Slavov Nikolai
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.802.9
Subject(s) - proteome , biology , proteomics , transcriptome , computational biology , phenotype , cell , embryonic stem cell , cell type , systems biology , cell fate determination , human proteome project , cellular differentiation , microbiology and biotechnology , gene , gene expression , genetics , transcription factor
Cellular heterogeneity is important to biological processes, including cancer and development. However, proteome heterogeneity is largely unexplored because of the limitations of existing methods for quantifying protein levels in single cells. To alleviate these limitations, we developed Single Cell ProtEomics by Mass Spectrometry (SCoPE‐MS), and validated its ability to identify distinct human cancer cell types based on their proteomes. We used SCoPE‐MS to quantify over a thousand proteins in differentiating mouse embryonic stem (ES) cells. The single‐cell proteomes enabled us to deconstruct cell populations and infer protein abundance relationships. Comparison between single‐cell proteomes and transcriptomes indicated coordinated mRNA and protein covariation. Yet many genes exhibited functionally concerted and distinct regulatory patterns at the mRNA and the protein levels, suggesting that post‐transcriptional regulatory mechanisms contribute to proteome remodeling during lineage specification, especially for developmental genes. SCoPE‐MS is broadly applicable to measuring proteome configurations of single cells and linking them to functional phenotypes, such as cell type and differentiation potentials. Support or Funding Information Northeastern University NIH New Innovator Award DP2GM123497 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .