Mass-spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation

Abstract

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.

References in corpus (5)

• A Random Matrix Approach to Cross-Correlations in Financial Data
• Mass-spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation
• Post-transcriptional regulation across human tissues
• Differential stoichiometry among core ribosomal proteins
• Routinely quantifying single cell proteomes: A new age in quantitative biology and medicine

Cited by in corpus (8)

• Mass-spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation
• Post-transcriptional regulation across human tissues
• Initial recommendations for performing, benchmarking, and reporting single-cell proteomics experiments
• Single-cell protein analysis by mass-spectrometry
• Routinely quantifying single cell proteomes: A new age in quantitative biology and medicine
• Sampling the proteome by emerging single-molecule and mass-spectrometry methods
• Quantifying homologous proteins and proteoforms
• Analyzing ribosome remodeling in health and disease