Compartmentalization of biological processes is a fundamental principle of eukaryotic cells that gathers the relevant molecules and enables multiple processes to occur in parallel. Despite a great deal of research, basic questions about the spatial organization of many proteins and biological processes remain unanswered. The Cell Atlas aims to systematically localize the human proteome using an antibody-based approach as part of the Human Protein Atlas project.

Data generation include automated sample preparation, high-resolution confocal microscopy and computational image analysis. An integrative approach with strict validation criteria is used including gene silencing, paired antibodies and fluorescently tagged proteins. This allows identification of novel protein components of both known and unknown cellular structures.

In total, over 12000 human proteins have been localized to 25 organelles and cellular structures. As much as 50% of all proteins localize to multiple compartments and 20% show cell cycle dependent expression. The high spatial resolution allows pinpointing of protein localization to fine structures such as the cytokinetic bridge, microtubule ends, nuclear bodies, and rods and rings. 

Here we discuss the importance of spatial proteomics for cell biology and present the content of the Cell Atlas as well as the path ahead to define the human organelle proteomes. 

This research was supported by grants from Knut and Alice Wallenbergs foundation.