Defining an essential transcription factor program for naïve pluripotency

• DOI: 10.1126/science.1248882
• Publication Date: 2014-06-05T18:25:59Z
• Authors: S.-J. Dunn; G. Martello; B. Yordanov; S. Emmott; A. G. Smith
• Keywords: Pluripotent Stem Cells; 0301 basic medicine; Mice; 03 medical and health sciences; Gene Expression Regulation; Cell Culture Techniques; Animals; Computational Biology; Gene Regulatory Networks; Embryonic Stem Cells; Transcription Factors

The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast has yet to be distilled into an executive molecular program. We developed a data-constrained, computational approach reduce complexity derive set of functionally validated components interaction combinations sufficient explain observed ES cell behavior. This minimal set, the simplest version comprises only 16 interactions, 12 components, three inputs, satisfies all prior specifications for furthermore predicts unknown nonintuitive responses compound genetic perturbations with overall accuracy 70%. propose that propagation identity is not determined by interactome but rather can explained relatively simple process computation.