Spatiotemporal dissection of the cell cycle with single-cell proteogenomics

Area of Science:

• Cell Biology
• Proteomics
• Genomics

Background:

• The cell cycle governs cell growth and division, crucial for life.
• Dysregulation of the cell cycle is implicated in diseases like cancer.
• Existing research lacks systematic analysis of cell-to-cell proteomic variability.

Purpose of the Study:

• To create a comprehensive spatiotemporal map of human proteomic heterogeneity.
• To investigate cell-to-cell variability in protein levels during the cell cycle.
• To identify proteins associated with mitosis and their potential oncogenic functions.

Main Methods:

• Integration of proteomics at subcellular resolution with single-cell transcriptomics.
• Precise temporal measurements of individual cells within the cell cycle.
• Analysis of proteomic and transcriptomic data to identify cell-to-cell variability.

Main Results:

• Approximately 20% of the human proteome exhibits cell-to-cell variability.
• Hundreds of proteins with novel associations to mitosis and the cell cycle were identified.
• Cell cycle progression accounts for less than half of observed cell-to-cell variability; most proteins are regulated post-translationally.
• Kinase-mediated phosphorylation differs between cycling and non-cycling variable proteins, impacting cell fate and metabolism.

Conclusions:

• The study provides a detailed proteomic map of the cell cycle, highlighting significant cell-to-cell heterogeneity.
• Identified proteins with potential oncogenic functions warrant further investigation in cancer research.
• The findings emphasize the importance of post-translational modifications in regulating protein levels during the cell cycle.