Embryonic stem (ES) cells are capable of continuous self-renewal and pluripotential differentiation. A "core" set of tran-scription factors, Oct4, Sox2, and Nanog, maintains the ES cell state, whereas various combinations of factors, invariablyincluding Oct4 and Sox2, reprogram somatic cells to pluripotency. We have sought to define the transcriptional network con-trolling pluripotency in mouse ES cells through combined proteomic and genomic approaches. We constructed a protein inter-action network surrounding Nanog and determined gene targets of the core and reprogramming factors, plus others. Theexpanded transcriptional network we have constructed forms the basis for further studies of directed differentiation and lin-eage reprogramming, and a paradigm for comprehensive elucidation of regulatory pathways in other stem cells.
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