ArticleMolecular systems biology2021
MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback.
Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Molecular signatures of cell diversity modulated by long noncoding RNAs in the human fetal spinal cord.iScience · 2026Article
- miRNA modules for precise, tunable control of gene expression.bioRxiv : the preprint server for biology · 2025Article
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- Mathematical Modeling for Oscillations Driven by Noncoding RNAs.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Kinetic modelling reveals the presence of multistability in normal and stressful conditions in translational initiation mechanism.PloS one · 2025Article
- High-throughput microRNA sequencing in the developing branchial arches suggests miR-92b-3p regulation of a cardiovascular gene network.Frontiers in genetics · 2025Article
- Widespread biochemical reaction networks enable Turing patterns without imposed feedback.Nature communications · 2024Article
- Elucidation of how the Mir-23-27-24 cluster regulates development and aging.Experimental & molecular medicine · 2024Review
- A logic-incorporated gene regulatory network deciphers principles in cell fate decisions.eLife · 2024Article
- Control of cell state transitions by post-transcriptional regulation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- LncRNAiScience · 2024Article
- Effects of microRNA-mediated negative feedback on gene expression noise.Biophysical journal · 2023Article
- Theoretical and computational tools to model multistable gene regulatory networks.Reports on progress in physics. Physical Society (Great Britain) · 2023Review
- MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.Molecular therapy. Nucleic acids · 2023Article
- Transcription ofJournal of developmental biology · 2023Article
- Critical Considerations for Investigating MicroRNAs during Tumorigenesis: A Case Study in Conceptual and Contextual Nuances of miR-211-5p in Melanoma.Epigenomes · 2023Review
- Origin, heterogeneity, and interconversion of noncanonical bistable switches from the positive feedback loops under dual signaling.iScience · 2023Article
- A quantitative evaluation of topological motifs and their coupling in gene circuit state distributions.iScience · 2023Article
- Single-cell transcriptomic analysis reveals diversity within mammalian spinal motor neurons.Nature communications · 2023Article
- Cooperative RNA degradation stabilizes intermediate epithelial-mesenchymal states and supports a phenotypic continuum.iScience · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Positive feedback driven by transcriptional regulation has long been considered a key mechanism underlying cell lineage segregation during embryogenesis. Using the developing spinal cord as a paradigm, we found that canonical, transcription-driven feedback cannot explain robust lineage segregation of motor neuron subtypes marked by two cardinal factors, Hoxa5 and Hoxc8. We propose a feedback mechanism involving elementary microRNA-mRNA reaction circuits that differ from known feedback loop-like structures. Strikingly, we show that a wide range of biologically plausible post-transcriptional regulatory parameters are sufficient to generate bistable switches, a hallmark of positive feedback. Through mathematical analysis, we explain intuitively the hidden source of this feedback. Using embryonic stem cell differentiation and mouse genetics, we corroborate that microRNA-mRNA circuits govern tissue boundaries and hysteresis upon motor neuron differentiation with respect to transient morphogen signals. Our findings reveal a previously underappreciated feedback mechanism that may have widespread functions in cell fate decisions and tissue patterning.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.