Quantitative Proteomics of Protein Complexes and Their Implications for Cell Reprograming and Pluripotency

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.