Abstract
BackgroundReprogramming of somatic cells for derivation of either embryonic stem (ES) cells, by somatic cell nuclear transfer (SCNT), or ES-like cells, by induced pluripotent stem (iPS) cell procedure, provides potential routes toward non-immunogenic cell replacement therapies. Nucleolar proteins serve as markers for activation of embryonic genes, whose expression is crucial for successful reprogramming. Although Nucleolin (Ncl) is one of the most abundant nucleolar proteins, its interaction partners in ES cells have remained unidentified.MethodologyHere we explored novel Ncl-interacting proteins using in situ proximity ligation assay (PLA), colocalization and immunoprecipitation (IP) in ES cells.Principal FindingsWe found that phosphorylated Ncl (Ncl-P) interacted with translationally controlled tumor protein (Tpt1) in murine ES cells. The Ncl-P/Tpt1 complex peaked during mitosis and was reduced upon retinoic acid induced differentiation, signifying a role in cell proliferation. In addition, we showed that Ncl-P interacted with the transcription factor Oct4 during interphase in human as well as murine ES cells, indicating of a role in transcription. The Ncl-P/Oct4 complex peaked during early stages of spontaneous human ES cell differentiation and may thus be involved in the initial differentiation event(s) of mammalian development.ConclusionsHere we described two novel protein-protein interactions in ES cells, which give us further insight into the complex network of interacting proteins in pluripotent cells.
Highlights
Nuclear reprogramming of somatic cells is a promising route in cell replacement therapy that can be used to replace or restore normal function of damaged cells
The molecular mechanisms of nuclear reprogramming are still unsolved recent reports have shown that reprogramming of human somatic cells can be achieved in vitro by retroviral expression of four transcription factors creating induced pluripotent stem cells, which are comparable to embryonic stem (ES) cells [1,2,3,4]
Even though Ncl is expressed at high levels in ES cells, not much is known about its specific role or physical interaction network in this cell type; we explored Ncl in ES cells, starting with a search for new interaction partners
Summary
Nuclear reprogramming of somatic cells is a promising route in cell replacement therapy that can be used to replace or restore normal function of damaged cells. The molecular mechanisms of nuclear reprogramming are still unsolved recent reports have shown that reprogramming of human somatic cells can be achieved in vitro by retroviral expression of four transcription factors creating induced pluripotent stem (iPS) cells, which are comparable to ES cells [1,2,3,4]. Successful reprogramming of somatic cells requires proper embryonic genome activation. Reprogramming of somatic cells for derivation of either embryonic stem (ES) cells, by somatic cell nuclear transfer (SCNT), or ES-like cells, by induced pluripotent stem (iPS) cell procedure, provides potential routes toward nonimmunogenic cell replacement therapies. Nucleolar proteins serve as markers for activation of embryonic genes, whose expression is crucial for successful reprogramming. Nucleolin (Ncl) is one of the most abundant nucleolar proteins, its interaction partners in ES cells have remained unidentified
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