Nanog induced intermediate state in regulating stem cell differentiation and reprogramming
| Autor: | Peijia Yu, Lei Zhang, Chao Tang, Qing Nie |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Homeobox protein NANOG Pluripotent Stem Cells Bioinformatics Cellular differentiation Systems biology Gene regulatory network Stem cells Biology Nanog Models Biological 03 medical and health sciences Structural Biology Cell differentiation Gene Regulatory Networks Induced pluripotent stem cell Molecular Biology Gene lcsh:QH301-705.5 Other Medical and Health Sciences Applied Mathematics SOXB1 Transcription Factors Cell Differentiation Nanog Homeobox Protein Gene network Cellular Reprogramming Computer Science Applications Cell biology 030104 developmental biology lcsh:Biology (General) Modeling and Simulation embryonic structures Stem cell Energy Metabolism Reprogramming Intermediate cellular state Octamer Transcription Factor-3 Research Article iPS cell reprogramming |
| Zdroj: | BMC Systems Biology BMC Systems Biology, Vol 12, Iss 1, Pp 1-13 (2018) Yu, Peijia; Nie, Qing; Tang, Chao; & Zhang, Lei. (2018). Nanog induced intermediate state in regulating stem cell differentiation and reprogramming.. BMC systems biology, 12(1), 22. doi: 10.1186/s12918-018-0552-3. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/3xw9t7g5 |
| ISSN: | 1752-0509 |
| Popis: | Background Heterogeneous gene expressions of cells are widely observed in self-renewing pluripotent stem cells, suggesting possible coexistence of multiple cellular states with distinct characteristics. Though the elements regulating cellular states have been identified, the underlying dynamic mechanisms and the significance of such cellular heterogeneity remain elusive. Results We present a gene regulatory network model to investigate the bimodal Nanog distribution in stem cells. Our model reveals a novel role of dynamic conversion between the cellular states of high and low Nanog levels. Model simulations demonstrate that the low-Nanog state benefits cell differentiation through serving as an intermediate state to reduce the barrier of transition. Interestingly, the existence of low-Nanog state dynamically slows down the reprogramming process, and additional Nanog activation is found to be essential to quickly attaining the fully reprogrammed cell state. Conclusions Nanog has been recognized as a critical pluripotency gene in stem cell regulation. Our modeling results quantitatively show a dual role of Nanog during stem cell differentiation and reprogramming, and the importance of the intermediate state during cell state transitions. Our approach offers a general method for analyzing key regulatory factors controlling cell differentiation and reprogramming. Electronic supplementary material The online version of this article (10.1186/s12918-018-0552-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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