Synthetic lateral inhibition governs cell-type bifurcation with robust ratios

Research output: Contribution to journalResearch articleContributedpeer-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 languageEnglish
Pages (from-to)6195
JournalNature communications
Volume6
Publication statusPublished - 5 Feb 2015
Peer-reviewedYes

External IDs

Scopus 84923206665

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