학술논문

Gene Expression Noise Enhances Robust Organization of the Early Mammalian Blastocyst
Document Type
article
Source
PLOS Computational Biology. 13(1)
Subject
Biochemistry and Cell Biology
Biomedical and Clinical Sciences
Biological Sciences
1.1 Normal biological development and functioning
Animals
Blastocyst
Cell Differentiation
Cell Plasticity
Cells
Cultured
Computer Simulation
Embryonic Development
Gene Expression Regulation
Developmental
Humans
Mice
Models
Biological
Models
Statistical
Signal-To-Noise Ratio
Stochastic Processes
Mathematical Sciences
Information and Computing Sciences
Bioinformatics
Language
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.