Dynamics of Single-Cell Protein Covariation during Epithelial-Mesenchymal Transition

Area of Science:

• Cell Biology
• Systems Biology
• Proteomics

Background:

• Physiological processes, including epithelial-mesenchymal transition (EMT), involve complex protein interaction networks.
• Changes in protein interactions may be more informative than average protein abundance for understanding cellular dynamics.
• Single-cell analysis provides a powerful lens to observe heterogeneity in biological systems.

Purpose of the Study:

• To investigate whether protein covariation within cellular clusters better reflects dynamic changes during physiological transitions compared to average protein abundance.
• To explore the utility of protein correlation dynamics in single cells for identifying functional protein modules.

Main Methods:

• Quantification of proteins in individual human cells undergoing EMT.
• Application of covariation analysis to protein data from single cells.
• Temporal analysis of protein-protein correlations within functionally coherent clusters.

Main Results:

• Functionally coherent protein clusters exhibited dynamic changes in protein-protein correlations during EMT.
• These correlation dynamics occurred without significant changes in the average protein abundance of the clusters.
• The observed protein correlation dynamics were monotonic over time and identified specific protein modules involved in actin cytoskeleton organization, energy metabolism, and protein transport.

Conclusions:

• Protein correlation dynamics in single cells offer a sensitive measure of biological regulation during physiological transitions.
• This approach reveals functional protein modules and regulatory mechanisms that are masked by analyzing average protein abundance.
• Single-cell protein covariation analysis provides a valuable window into dynamic cellular processes.