title: Gene Expression Noise Enhances Robust Organization of the Early Mammalian Blastocyst.
abstract: A critical event in mammalian embryo development is construction of an inner cell mass surrounded by a trophoectoderm (a shell of cells that later form extraembryonic structures). We utilize multi-scale, stochastic modeling to investigate the design principles responsible for robust establishment of these structures. This investigation makes three predictions, each supported by our quantitative imaging. First, stochasticity in the expression of critical genes promotes cell plasticity and has a critical role in accurately organizing the developing mouse blastocyst. Second, asymmetry in the levels of noise variation (expression fluctuation) of Cdx2 and Oct4 provides a means to gain the benefits of noise-mediated plasticity while ameliorating the potentially detrimental effects of stochasticity. Finally, by controlling the timing and pace of cell fate specification, the embryo temporally modulates plasticity and creates a time window during which each cell can continually read its environment and adjusts its fate. These results suggest noise has a crucial role in maintaining cellular plasticity and organizing the blastocyst.
authors.affiliation: Department of Physics and Astronomy, Vanderbilt University, Nashville TN, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Holmes
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Nabora Soledad
authors.initials: NS
authors.lastname: Reyes de Mochel
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Mathematics, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Qixuan
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Mathematics, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Huijing
authors.initials: H
authors.lastname: Du
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Mathematics, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Chiang
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Olivier
authors.initials: O
authors.lastname: Cinquin
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Ken
authors.initials: K
authors.lastname: Cho
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA, United States of America.|Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, United States of America.|Department of Mathematics, University of California, Irvine, Irvine, CA, United States of America.
authors.forename: Qing
authors.identifier: 0000-0002-8804-3368
authors.initials: Q
authors.lastname: Nie
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D000066670:Cell Plasticity / Q000502:physiology; D002478:Cells, Cultured; D003198:Computer Simulation; D047108:Embryonic Development / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D059629:Signal-To-Noise Ratio; D013269:Stochastic Processes