Compartmentalization of biological reactions in time and space is an important mechanism to allow multiple cellular reactions to occur in parallel. Thus, resolving the spatiotemporal cellular distribution of the human proteome would greatly increase our understanding of human biology and disease. We have previously generated a high-resolution map of the subcellular distribution of the human proteome as part of the open access Human Protein Atlas database. We have shown that as much as half of all proteins localize to multiple compartments. Such proteins may have context specific functions and ‘moonlight’ in different parts of the cell, thus increasing the functionality of the proteome and the complexity of the cell from a systems perspective. Recently we turned to single cell analysis to identify proteins with potential temporal variability in expression. We identify 17% of the human proteome to display cell-to-cell variability, of which we could attribute 25% as correlated to cell cycle progression and present the first evidence of cell cycle association for 258 proteins. A key finding is that the variance, of many of the cell cycle associated proteins, is only partially explained by the cell cycle, which hints at extensive cross-talk between the cell cycle and other signaling pathways. Single cell sequencing data further demonstrates that only 18 % of these proteins are temporally regulated at the transcript level, indicating that the majority of the novel cell cycle proteins are subjected to translational or post-translational temporal regulation.
In summary, I will demonstrate the importance of spatial proteomics data for improved single cell biology.