論文 - 詳細
RRC ID | 36055 |
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著者 | Matsuda M, Koga M, Woltjen K, Nishida E, Ebisuya M. |
タイトル | Synthetic lateral inhibition governs cell-type bifurcation with robust ratios. |
ジャーナル | 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. |
巻・号 | 6 |
ページ | 6195 |
公開日 | 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 |
引用数 | 37 |
WOS 分野 | CELL BIOLOGY |
リソース情報 | |
遺伝子材料 | pGa981-6 (RDB06776) |
ヒト・動物細胞 | CHO-K1(RCB0285) |