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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 14, 2021 |
| Title |
Noncanonical post-transcriptional feedback between microRNA and messenger RNA enables bistability and governs robust cell fate decisions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Single cell RNA seq of e12.5 mouse spinal motor neurons at cervical segment (C2-T1). Motor neurons were labeled in GFP and sorted via FACS, pooled and loaded onto 10x Genomics Single Cell 3’ Chip as a single sample.
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| Contributor(s) |
Liau ES, Chen JA |
| Citation |
Li C-J, Liau ES, Lee Y-H, Huang Y-Z, Liu Z, Willems A, Garside V, McGlinn E, Chen J-A, and Hong T. MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback. Mol Syst Biol (2021);17:e9945.
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| Submission date |
Aug 11, 2020 |
| Last update date |
Apr 15, 2021 |
| Contact name |
Jun-An Chen |
| E-mail(s) |
jachen@imb.sinica.edu.tw
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| Organization name |
Academia Sinica
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| Department |
Institute of Molecular Biology
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| Lab |
N517
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| Street address |
128 Academia Road, Section 2
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| City |
Taipei |
| ZIP/Postal code |
11529 |
| Country |
Taiwan |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (1) |
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| Relations |
| BioProject |
PRJNA656449 |
| SRA |
SRP277028 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE156023_RAW.tar |
143.2 Mb |
(http)(custom) |
TAR (of CSV, MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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