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Quantifying the Waddington landscape and biological paths for development and differentiation

Wang, Jin ; Zhang, Kun ; Xu, Li ; Wang, Erkang

Proceedings of the National Academy of Sciences - PNAS, 2011-05, Vol.108 (20), p.8257-8262 [Periódico revisado por pares]

United States: National Academy of Sciences

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  • Título:
    Quantifying the Waddington landscape and biological paths for development and differentiation
  • Autor: Wang, Jin ; Zhang, Kun ; Xu, Li ; Wang, Erkang
  • Assuntos: Animals ; Basins ; Biological Sciences ; Biology ; Cell Dedifferentiation ; Cell Differentiation ; Cell Lineage ; Cells ; Cellular differentiation ; China ; Correlation analysis ; Curl ; Developmental biology ; Humans ; Kinetics ; Land development ; Models, Biological ; Models, Theoretical ; Multipotent stem cells ; Physical Sciences ; probability ; Probability distribution ; Progenitor cells ; Stem cells ; Stem Cells - cytology ; Transcription factors
  • É parte de: Proceedings of the National Academy of Sciences - PNAS, 2011-05, Vol.108 (20), p.8257-8262
  • Notas: http://dx.doi.org/10.1073/pnas.1017017108
    Author contributions: J.W. and E.W. designed research; J.W., K.Z., and L.X. performed research; J.W. and E.W. contributed new reagents/analytic tools; J.W., K.Z., L.X., and E.W. analyzed data; and J.W., K.Z., L.X., and E.W. wrote the paper.
    Edited* by José N. Onuchic, University of California, La Jolla, CA, and approved March 18, 2011 (received for review November 11, 2010)
  • Descrição: We developed a theoretical framework to prove the existence and quantify the Waddington landscape as well as chreode-biological paths for development and differentiation. The cells can have states with the higher probability ones giving the different cell types. Different cell types correspond to different basins of attractions of the probability landscape. We study how the cells develop from undifferentiated cells to differentiated cells from landscape perspectives. We quantified the Waddington landscape through construction of underlying probability landscape for cell development. We show the developmental process proceeds as moving from undifferentiated to the differentiated basins of attractions. The barrier height of the basins of attractions correlates with the escape time that determines the stability of cell types. We show that the developmental process can be quantitatively described and uncovered by the biological paths on the quantified Waddington landscape from undifferentiated to the differentiated cells. We found the dynamics of the developmental process is controlled by a combination of the gradient and curl force on the landscape. The biological paths often do not follow the steepest descent path on the landscape. The landscape framework also quantifies the possibility of reverse differentiation process such as cell reprogramming from differentiated cells back to the original stem cell. We show that the biological path of reverse differentiation is irreversible and different from the one for differentiation process. We found that the developmental process described by the underlying landscape and the associated biological paths is relatively stable and robust against the influences of environmental perturbations.
  • Editor: United States: National Academy of Sciences
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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