Reprogramming, oscillations and transdifferentiation in epigenetic landscapes

被引:9
|
作者
Kaity, Bivash [1 ]
Sarkar, Ratan [2 ]
Chakrabarti, Buddhapriya [3 ]
Mitra, Mithun K. [1 ]
机构
[1] Indian Inst Technol, Dept Phys, Bombay 400076, Maharashtra, India
[2] Indian Inst Sci, Ctr High Energy Phys, Bangalore 560012, Karnataka, India
[3] Univ Sheffield, Dept Phys & Astron, Sheffield S3 7RH, S Yorkshire, England
来源
SCIENTIFIC REPORTS | 2018年 / 8卷
关键词
PLURIPOTENT STEM-CELLS; TRANSCRIPTIONAL REGULATION; DIRECT CONVERSION; HUMAN FIBROBLASTS; LINEAGE CHOICE; EXPRESSION; PU.1; DIFFERENTIATION; BISTABILITY; CHROMOSOMES;
D O I
10.1038/s41598-018-25556-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Waddington's epigenetic landscape provides a phenomenological understanding of the cell differentiation pathways from the pluripotent to mature lineage-committed cell lines. In light of recent successes in the reverse programming process there has been significant interest in quantifying the underlying landscape picture through the mathematics of gene regulatory networks. We investigate the role of time delays arising from multi-step chemical reactions and epigenetic rearrangement on the cell differentiation landscape for a realistic two-gene regulatory network, consisting of self-promoting and mutually inhibiting genes. Our work provides the first theoretical basis of the transdifferentiation process in the presence of delays, where one differentiated cell type can transition to another directly without passing through the undifferentiated state. Additionally, the interplay of time-delayed feedback and a time dependent chemical drive leads to long-lived oscillatory states in appropriate parameter regimes. This work emphasizes the important role played by time-delayed feedback loops in gene regulatory circuits and provides a framework for the characterization of epigenetic landscapes.
引用
收藏
页数:12
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