title: Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide cheater screen.
abstract: Ensuring cooperation among formerly autonomous cells has been a central challenge in the evolution of multicellular organisms. One solution is monoclonality, but this option still leaves room for exploitative behavior, as it does not eliminate genetic and epigenetic variability. We therefore hypothesized that embryonic development must be protected by robust regulatory mechanisms that prevent aberrant clones from superseding wild-type cells. Using a genome-wide screen in murine induced pluripotent stem cells, we identified a network of genes (centered on p53, topoisomerase 1, and olfactory receptors) whose down-regulation caused the cells to replace wild-type cells in vitro and in the mouse embryo--without perturbing normal development. These genes thus appear to fulfill an unexpected role in fostering cell cooperation.
authors.affiliation: Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Marion
authors.initials: M
authors.lastname: Dejosez
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ura
authors.forename: Vicky L
authors.initials: VL
authors.lastname: Brandt
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Zwaka
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D054338:Cell Transdifferentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D015536:Down-Regulation; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D055106:Genome-Wide Association Study; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D051379:Mice; D009154:Mutation; D018035:Receptors, Odorant / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D018035:Receptors, Odorant; D016159:Tumor Suppressor Protein p53; D004264:DNA Topoisomerases, Type I