Deciphering protein complexes and protein interaction networks for stem cell pluripotency

Embryonic stem cells (ESCs) hold great promise in regenerative medicine owing to their unique property of unlimited self-renewal while retaining multilineage differentiation capacities. Stem cell biology has been advanced by high throughput genomics and proteomics approaches toward identifying a fuller repertoire of genetic and epigenetic regulatory factors and understanding how they function individually and/or combinatorially in regulating self-renewal and maintaining pluripotency. Proteins function as members of protein complexes and form a myriad of protein-protein interactions in governing proper transcriptional output and cellular identity. Construction of protein-protein interaction networks together with other large datasets such as expression profiles and target gene occupancy is essential in facilitating a comprehensive understanding of the mechanisms of ESC self-renewal and pluripotency. This chapter will summarize current efforts and ongoing progresses in dissecting the protein complexes and mapping the protein interaction networks associated with the major pluripotency factors Nanog, Oct4 and Sox2, and provide guidance for refining the current methodologies and developing new tools for high throughput data generation to further our understanding of stem cell pluripotency.