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Exploring the underlying mechanisms of the coupling between cell differentiation and cell cycle

J Phys Chem B. 2019 Apr 25;123(16):3490-3498. doi: 10.1021/acs.jpcb.9b00509. Epub 2019 Apr 11.

Abstract

Differentiation and replication are the two major fates of the cells. They are the fundamental processes for completing the cellular functions. Although the underlying biological processes have been considerably explored for each of these processes and significant progresses have been made, global quantification and physical understanding are still challenging, especially for the relationship among them. In this study, we developed a theoretical framework for both the cell cycle and cell differentiation by exploring the associated global dynamics and their underlying relationship. We found that the dynamics of the cell cycle and cell differentiation is governed by both the landscape gradient and rotational curl flux. While landscape attracts the system down to the stable state basins, the curl flux drives the stable oscillation flow. We uncovered the irregular sombrero-shaped landscapes of the cell cycle at different developmental stages. We studied how the cells develop from undifferentiated cells to differentiated cells and how the cell cycle proceeds at different developmental stages. We investigated how the cell differentiation can influence the cell cycle where more progressive differentiation can lead to the changes of the cell cycle oscillations. In contrast, we can also quantitatively illustrate how the cell cycle can influence the cell differentiation where cell cycle regulation can lead to the changes of the differentiation processes. Through the landscape and flux analysis, we uncovered the key regulatory elements controlling the progression of the cell differentiation and cell cycle. This can help to design an effective strategy for drug discovery against associated diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Cycle*
  • Cell Differentiation*
  • Gene Regulatory Networks
  • Models, Biological*