Synthetic lateral inhibition governs cell-type bifurcation with robust ratios
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
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Pages (from-to) | 6195 |
Journal | Nature communications |
Volume | 6 |
Publication status | Published - 5 Feb 2015 |
Peer-reviewed | Yes |
External IDs
Scopus | 84923206665 |
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Keywords
Keywords
- Animals, CHO Cells, Cell Communication/genetics, Cell Differentiation/genetics, Cell Engineering, Cricetulus, Feedback, Physiological, Gene Expression Regulation, Genes, Reporter, Genetic Vectors, Glycosyltransferases/genetics, Green Fluorescent Proteins/genetics, Intracellular Signaling Peptides and Proteins/genetics, Lentivirus/genetics, Luciferases/genetics, Luminescent Proteins/genetics, Membrane Proteins/genetics, Mice, Neural Stem Cells/cytology, Receptors, Notch/genetics, Signal Transduction, Time Factors, Transcription, Genetic, Red Fluorescent Protein