title: Quantitative proteomics of protein complexes and their implications for cell reprograming and pluripotency.
abstract: Pluripotency of embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs) and reprograming of somatic cells (SCs) to pluripotency are governed by known and unknown factors. These factors, including protein complexes, are poorly described at the proteome level. Here, we established the quantitative proteomic profiles across three types of cells (iPSCs, ESCs, and SCs) using OFFGEL fractionation coupled with LTQ-Orbitrp analysis. Additionally, we utilized the previously published proteomic profiles of iPSCs, ESCs, and SCs. By integrating these proteomic profiles with protein-protein interaction resources, we identified numerous protein complexes in iPSCs and/or ESCs, which include known and novel chromatin remodeling complexes that facilitate cell reprograming. The identified protein complexes also include the previously unreported ones that are associated with the imperfect aspects of iPSCs or cell reprograming process. Further, we performed a comparison between our study and previously published studies and highlighted a partial conservation of the identified protein complexes across the iPSCs generated by different laboratories and iPS cell-type specific protein complexes. The identified protein complexes were validated by integrated in silico analysis of microarray repository data related to ESCs differentiation into embryoid bodies. A majority of the protein complexes exhibited significant (p < 0.005) co-regulation of their components upon ESC differentiation, suggesting their role in the maintenance of the pluripotent state. Finally, we showed a link between the components of the protein complexes and embryonic development using the existing loss-of-function phenotype data. Together, our integrated approach provides the first comprehensive view of the protein complexes that may have implications for cell reprograming and pluripotency.
authors.affiliation: Genomics Research Center and ‡Institute of Cellular and Organismic Biology, Academia Sinica , Taipei 11529, Taiwan.
authors.forename: Putty-Reddy
authors.initials: PR
authors.lastname: Sudhir
authors.forename: Madireddy Pavana
authors.initials: MP
authors.lastname: Kumari
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hsu
authors.forename: Julien
authors.initials: J
authors.lastname: Massiot
authors.forename: Chein-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Hung-Chih
authors.initials: HC
authors.lastname: Kuo
authors.forename: Chung-Hsuan
authors.initials: CH
authors.lastname: Chen
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D046228:Microarray Analysis; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics
chemical_list: D011506:Proteins