RRC ID 36055
Author Matsuda M, Koga M, Woltjen K, Nishida E, Ebisuya M.
Title Synthetic lateral inhibition governs cell-type bifurcation with robust ratios.
Journal Nat Commun
Abstract 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.
Volume 6
Pages 6195
Published 2015-2-5
DOI 10.1038/ncomms7195
PII ncomms7195
PMID 25652697
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
IF 12.121
Times Cited 37
DNA material pGa981-6 (RDB06776)
Human and Animal Cells CHO-K1(RCB0285)