MicroRNA governs bistable cell differentiation and lineage segregation via a noncanonical feedback

Autor: Andrew Willems, Ziyi Liu, Ee Shan Liau, Jun-An Chen, Tian Hong, Yang-Zhe Huang, Yi-Han Lee, Victoria C. Garside, Chung-Jung Li, Edwina McGlinn
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Medicine (General)
Bistability
Transcription
Genetic
Cellular differentiation
0302 clinical medicine
single‐cell RNA sequencing
Gene Regulatory Networks
positive feedback loop
RNA-Seq
Biology (General)
Feedback
Physiological
Motor Neurons
0303 health sciences
Applied Mathematics
Cell Differentiation
Articles
RNA Biology
medicine.anatomical_structure
Computational Theory and Mathematics
Spinal Cord
Female
Single-Cell Analysis
General Agricultural and Biological Sciences
Information Systems
Morphogen
Signal Transduction
Lineage (genetic)
QH301-705.5
Tretinoin
Biology
Models
Biological
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
R5-920
medicine
Animals
Cell Lineage
RNA
Messenger
030304 developmental biology
Positive feedback
Homeodomain Proteins
General Immunology and Microbiology
post‐transcriptional regulation
Base Sequence
Mechanism (biology)
tissue boundary formation
motor neuron differentiation
Motor neuron
Embryonic stem cell
Mice
Inbred C57BL
Kinetics
MicroRNAs
Gene Expression Regulation
Neuroscience
Development & Differentiation
030217 neurology & neurosurgery
Transcription Factors
Zdroj: Molecular Systems Biology
Molecular Systems Biology, Vol 17, Iss 4, Pp n/a-n/a (2021)
ISSN: 1744-4292
Popis: 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.
Robust cell fate decision and precise tissue boundary formation are critical for development. This study reports a feedback mechanism involving mRNA‐microRNA interactions during cell lineage segregation in mouse spinal cord development.
Databáze: OpenAIRE
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