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
WOS Category CELL BIOLOGY
Altmetric score
オルトメトリクス指標項目
The most frequently cited source X(Twitter)
Total number of mentions 16
Altmetric score changes over past 6months 0.0
Resource
DNA material pGa981-6 (RDB06776)
Human and Animal Cells CHO-K1(RCB0285)