Reference - Detail
|Author||Matsuda M, Koga M, Woltjen K, Nishida E, Ebisuya M.|
|Title||Synthetic lateral inhibition governs cell-type bifurcation with robust ratios.|
Cell-type diversity in multicellular organisms is created through a series of binary cell fate decisions. Lateral inhibition controlled by Delta-Notch signalling is the core mechanism for the choice of alternative cell types by homogeneous neighbouring cells. Here, we show that cells engineered with a Delta-Notch-dependent lateral inhibition circuit spontaneously bifurcate into Delta-positive and Notch-active cell populations. The synthetic lateral inhibition circuit comprises transcriptional repression of Delta and intracellular feedback of Lunatic fringe (Lfng). The Lfng-feedback subcircuit, even alone, causes the autonomous cell-type bifurcation. Furthermore, the ratio of two cell populations bifurcated by lateral inhibition is reproducible and robust against perturbation. The cell-type ratio is adjustable by the architecture of the lateral inhibition circuit as well as the degree of cell-cell attachment. Thus, the minimum lateral inhibition mechanism between adjacent cells not only serves as a binary cell-type switch of individual cells but also governs the cell-type ratio at the cell-population level.
|MeSH||Animals CHO Cells Cell Communication / genetics* Cell Differentiation / genetics* Cell Engineering Cricetulus Feedback, Physiological Gene Expression Regulation Genes, Reporter Genetic Vectors Glycosyltransferases / genetics Glycosyltransferases / metabolism* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism* Lentivirus / genetics Lentivirus / metabolism Luciferases / genetics Luciferases / metabolism Luminescent Proteins / genetics Luminescent Proteins / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Neural Stem Cells / cytology Neural Stem Cells / metabolism* Receptors, Notch / genetics Receptors, Notch / metabolism* Signal Transduction Time Factors Transcription, Genetic|
|WOS Category||CELL BIOLOGY|
|DNA material||pGa981-6 (RDB06776)|
|Human and Animal Cells||CHO-K1(RCB0285)|