Speaker
Description
Waddington’s epigenetic landscape (EL) famously represents development as a ball rolling down a branching surface whose valleys correspond to cell fates, while the landscape itself is shaped by pegs and ropes representing gene interactions. Despite its enduring influence, which continues today in fields such as stem cell biology, aging and single-cell omics, the conceptual meaning of this metaphor remains ambiguous.
In this work we propose a systematic critical analysis of both Waddington’s original EL metaphor and its modern theoretical reinterpretations. At the metaphor level, a basic difficulty lies in the status of the “ball”, which is supposed to represent the evolving cell, while the landscape is shaped by the “ropes” (gene products). This creates a visual and conceptual separation between the cell and the regulatory system. At the theoretical level, several mathematical frameworks have been proposed to formalize the landscape idea, including geometric approaches based on dynamical systems and bifurcation theory \cite{Cislo2025}, potential–flux decompositions of non-equilibrium dynamics \cite{Wang2015} and stochastic quasi-potentials derived from large-deviation theory \cite{Newby2015}. We analyze the relevance of their underlying assumptions and show that these frameworks differ in essential ways from Waddington’s vision. Clarifying these conceptual differences helps assess the scope and limitations of the EL metaphor in contemporary theoretical biology
Bibliography
@article{Cislo2025,
title = {Reconstructing {Waddington}’s landscape from data},
volume = {122},
issn = {0027-8424, 1091-6490},
url = {https://pnas.org/doi/10.1073/pnas.2521762122},
doi = {10.1073/pnas.2521762122},
language = {en},
number = {49},
urldate = {2026-05-10},
journal = {Proceedings of the National Academy of Sciences},
author = {Cislo, Dillon J. and Delás, M. Joaquina and Briscoe, James and Siggia, Eric D.},
month = dec,
year = {2025},
pages = {e2521762122},
}
@article{Newby2015,
title = {Landscape and flux theory of non-equilibrium dynamical systems with application to biology},
volume = {64},
issn = {0001-8732, 1460-6976},
url = {http://www.tandfonline.com/doi/full/10.1080/00018732.2015.1037068},
doi = {10.1080/00018732.2015.1037068},
language = {en},
number = {1},
urldate = {2026-05-10},
journal = {Advances in Physics},
author = {Wang, Jin},
month = jan,
year = {2015},
pages = {1--137},
}
@article{Wang2015,
title = {Bistable switching asymptotics for the self regulating gene},
volume = {48},
issn = {1751-8113, 1751-8121},
url = {https://iopscience.iop.org/article/10.1088/1751-8113/48/18/185001},
doi = {10.1088/1751-8113/48/18/185001},
number = {18},
urldate = {2026-05-10},
journal = {Journal of Physics A: Mathematical and Theoretical},
author = {Newby, Jay},
month = may,
year = {2015},
pages = {185001},
}
