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Series GSE156023 Query DataSets for GSE156023
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
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. 
 
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.
 
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.
Submission date Aug 11, 2020
Last update date Apr 15, 2021
Contact name Jun-An Chen
E-mail(s) jachen@imb.sinica.edu.tw
Organization name Academia Sinica
Department Institute of Molecular Biology
Lab N517
Street address 128 Academia Road, Section 2
City Taipei
ZIP/Postal code 11529
Country Taiwan
 
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (1)
GSM4720584 e12.5 cervical motor neurons
Relations
BioProject PRJNA656449
SRA SRP277028

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Supplementary file Size Download File type/resource
GSE156023_RAW.tar 143.2 Mb (http)(custom) TAR (of CSV, MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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