title: Defining an essential transcription factor program for naïve pluripotency.
abstract: The gene regulatory circuitry through which pluripotent embryonic stem (ES) cells choose between self-renewal and differentiation appears vast and has yet to be distilled into an executive molecular program. We developed a data-constrained, computational approach to reduce complexity and to derive a set of functionally validated components and interaction combinations sufficient to explain observed ES cell behavior. This minimal set, the simplest version of which comprises only 16 interactions, 12 components, and three inputs, satisfies all prior specifications for self-renewal and furthermore predicts unknown and nonintuitive responses to compound genetic perturbations with an overall accuracy of 70%. We propose that propagation of ES cell identity is not determined by a vast interactome but rather can be explained by a relatively simple process of molecular computation.
authors.affiliation: Computational Science Laboratory, Microsoft Research, Cambridge, CB1 2FB, UK.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Dunn
authors.affiliation: Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 1QR, UK.
authors.forename: G
authors.initials: G
authors.lastname: Martello
authors.affiliation: Computational Science Laboratory, Microsoft Research, Cambridge, CB1 2FB, UK.
authors.forename: B
authors.initials: B
authors.lastname: Yordanov
authors.affiliation: Computational Science Laboratory, Microsoft Research, Cambridge, CB1 2FB, UK.
authors.forename: S
authors.initials: S
authors.lastname: Emmott
authors.affiliation: Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge, CB2 1QR, UK.|Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: A G
authors.initials: AG
authors.lastname: Smith
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D019295:Computational Biology; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D051379:Mice; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014157:Transcription Factors