The emergence of the two cell fates and their associated switching for a negative auto-regulating gene
| Autor: | Erkang Wang, Kun Zhang, Xiaona Fang, Zhenlong Jiang, Jin Wang, Li Tian, Qiong Liu, Qingzhe Dong |
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| Rok vydání: | 2019 |
| Předmět: |
Physiology
Molecular Networks (q-bio.MN) Self-repressor Cell Gene regulatory network Plant Science Cell fate determination Biology General Biochemistry Genetics and Molecular Biology Bimodality Gene product 03 medical and health sciences 0302 clinical medicine Bacterial Proteins Structural Biology Cell fate decision-making Gene expression Escherichia coli medicine Quantitative Biology - Molecular Networks Gene Regulatory Networks lcsh:QH301-705.5 Gene Ecology Evolution Behavior and Systematics 030304 developmental biology Regulation of gene expression 0303 health sciences food and beverages Cell Biology Phenotype Cell biology medicine.anatomical_structure lcsh:Biology (General) Gene Expression Regulation FOS: Biological sciences General Agricultural and Biological Sciences 030217 neurology & neurosurgery Research Article Transcription Factors Developmental Biology Biotechnology |
| Zdroj: | BMC Biology BMC Biology, Vol 17, Iss 1, Pp 1-14 (2019) |
| ISSN: | 1741-7007 |
| Popis: | Decisions in the cell that lead to its ultimate fate are important for cellular functions such as proliferation, growth, differentiation, development and death. Understanding this decision process is imperative for advancements in the treatment of diseases such as cancer. It is clear that underlying gene regulatory networks and surrounding environments of the cells are crucial for function. The self-repressor is a very abundant gene regulatory motif, and is often believed to have only one cell fate. In this study, we elucidate the effects of microenvironments mimicking the epigenetic effects on cell fates through the introduction of inducers capable of binding to a self-repressing gene product (protein), thus regulating the associated gene. This alters the effective regulatory binding speed of the self-repressor regulatory protein to its destination DNA without changing the gene itself. The steady state observations and real time monitoring of the self-repressor expression dynamics reveal the emergence of the two cell fates, The simulations are consistent with the experimental findings. We provide physical and quantitative explanations for the origin of the two phenotypic cell fates. We find that two cell fates, rather than a single fate, and their associated switching dynamics emerge from a change in effective gene regulation strengths. The switching time scale is quantified. Our results reveal a new mechanism for the emergence of multiple cell fates. This provides an origin for the heterogeneity often observed among cell states, while illustrating the influence of microenvironments on cell fates and their decision-making processes without genetic changes Comment: 19 pages, 4 figures |
| Databáze: | OpenAIRE |
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