SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation

TLDR

Quantifying thousands of proteins in single cells is essential for addressing key biological questions. The authors developed SCoPE‑MS to identify distinct human cancer cell types based on their proteomes. SCoPE‑MS quantifies over a thousand proteins per single mammalian cell, enabling identification of distinct cancer cell types and deconstruction of cell populations to infer protein abundance relationships in differentiating mouse embryonic stem cells. Single‑cell proteome–transcriptome comparison shows coordinated mRNA‑protein covariation, but many genes display distinct regulatory patterns at the mRNA and protein levels.

Abstract

Some exciting biological questions require quantifying thousands of proteins in single cells. To achieve this goal, we develop Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS) and validate its ability to identify distinct human cancer cell types based on their proteomes. We use SCoPE-MS to quantify over a thousand proteins in differentiating mouse embryonic stem cells. The single-cell proteomes enable us to deconstruct cell populations and infer protein abundance relationships. Comparison between single-cell proteomes and transcriptomes indicates coordinated mRNA and protein covariation, yet many genes exhibit functionally concerted and distinct regulatory patterns at the mRNA and the protein level.