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Reprogramming, oscillations and transdifferentiation in epigenetic landscapes

Kaity, Bivash and Sarkar, Ratan and Chakrabarti, Buddhapriya and Mitra, Mithun K (2018) Reprogramming, oscillations and transdifferentiation in epigenetic landscapes. In: SCIENTIFIC REPORTS, 8 .

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Official URL: https://dx.doi.org/10.1038/s41598-018-25556-9


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.

Item Type: Journal Article
Additional Information: Copyright of this article belong to NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Department/Centre: Division of Physical & Mathematical Sciences > Centre for High Energy Physics
Date Deposited: 04 Jul 2018 14:43
Last Modified: 04 Jul 2018 14:43
URI: http://eprints.iisc.ac.in/id/eprint/60146

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