Single-cell dynamics

Landscape–Flux
Framework

A visual guide to how cell states emerge, move, and change.

Explore the landscape
Interactive state space stochastic trajectories
Now viewingProgenitor basin
0°

Landscape

Stability shapes the space of possible cell states.

Flux

Non-equilibrium flow drives transitions between states.

Cell states

Attractors correspond to stable cellular phenotypes.

The central idea

One map. Two kinds of force.

A landscape shows where cells accumulate. Flux shows how probability keeps moving. You need both to reconstruct non-equilibrium dynamics.

A
Observed drift

Single-cell dynamics combine stabilization with directional, driven flow.

01

Infer the steady distribution

Estimate Pss(x) from a transition matrix, RNA-velocity field, optimal transport model, or an ensemble of trajectories.

02

Convert density into landscape

U(x) = −ln Pss(x). Deep basins mark frequently occupied, stable phenotypic regions.

03

Recover the missing direction

The steady current Jss distinguishes genuine circulation from equilibrium relaxation.

Quantitative laboratory

Compare two dynamical landscapes.

Switch between cell-cycle circulation and branching differentiation. Every basin reports its steady probability and relative potential; the controls update flux, transition rate, and entropy production.

U(x) = −ln Pss(x)Jₛₛ = 0.084
high Ustable limit-cycle troughG1P=0.45SP=0.28G2/MP=0.27
0.184 keff (a.u.⁻¹)0.084 |Jss|0.443tot (kB/a.u.)

Illustrative numerical model

Cell cycle

A nonzero cyclic current captures the arrow of cell-cycle progression even though the phase distribution is stationary.

StatePssU − Umin
G10.450.000
S0.280.474
G2/M0.270.511
Calculationkeff = exp(−ΔU‡/D) × drive factorValues are pedagogical and dimensionless—not fitted experimental estimates.

Mathematical core

Six equations to keep nearby.

These relations connect observed single-cell motion to probability, force, irreversibility, and transition paths.

Force decomposition

F = −D∇U + Jss / Pss

Gradient stabilizes. Flux circulates.

The first term follows the potential; the second is the non-equilibrium driving force.

Probability current

J = FP − D∇P

Drift transports probability while diffusion spreads it.

Continuity

tP = −∇·J

Probability changes wherever currents converge or diverge.

Landscape

U = −ln Pss

Highly occupied states become low-potential basins.

Entropy production

tot = ∫ JᵀD⁻¹JP dx ≥ 0

A global measure of time-reversal breaking and dissipation.

Path action

S[x] = ¼∫‖ẋ − F‖²D⁻¹dt

Lower-action paths are more probable transition routes.

Important

The landscape depends on coordinates, sampling, and the diffusion model. Treat it as an effective probabilistic potential, and test biological conclusions for robustness.

Lab reference

Shared language for the group.

Open any term for a collaborator-ready definition. The distinctions between density, current, and force are especially important.

DataDynamicsSteady stateLandscape + flux
01Attractor+

A stable region of state space toward which nearby cellular trajectories tend to move.

02Detailed balance+

The equilibrium condition in which every microscopic probability flow is balanced by its reverse, so Jₛₛ = 0.

03Landscape+

U = −ln Pₛₛ: a probabilistic potential derived from the steady-state distribution. It is not automatically a thermodynamic energy.

04Probability flux+

The directed current J that transports probability through state space. At steady state it can circulate even when P no longer changes.

05Barrier+

A high-potential region separating attractors; larger barriers generally imply rarer transitions, with a noise-dependent rate.

06Entropy production+

A nonnegative measure of irreversibility and energetic dissipation associated with sustained probability currents.

Selected literature

References

Foundational theory and recent single-cell applications of the landscape–flux framework.

  1. 01Jin Wang, Li Xu, and Erkang WangPotential landscape and flux framework of nonequilibrium networks: Robustness, dissipation, and coherence of biochemical oscillationsProceedings of the National Academy of Sciences · 2008 · DOI: 10.1073/pnas.0800579105
  2. 02Jin Wang, Kun Zhang, Li Xu, and Erkang WangQuantifying the Waddington landscape and biological paths for development and differentiationProceedings of the National Academy of Sciences · 2011 · DOI: 10.1073/pnas.1017017108
  3. 03Jin WangLandscape and flux theory of non-equilibrium dynamical systems with application to biologyAdvances in Physics · 2015 · DOI: 10.1080/00018732.2015.1037068
  4. 04Xiaona Fang, Karsten Kruse, Ting Lu, and Jin WangNonequilibrium physics in biologyReviews of Modern Physics · 2019 · DOI: 10.1103/RevModPhys.91.045004
  5. 05Ligang Zhu and Jin WangQuantifying Landscape-Flux via Single-Cell Transcriptomics Uncovers the Underlying Mechanism of Cell CycleAdvanced Science · 2024 · DOI: 10.1002/advs.202308879
  6. 06Ligang Zhu, Songlin Yang, Kun Zhang, Hong Wang, Xiaona Fang, and Jin WangUncovering underlying physical principles and driving forces of cell differentiation and reprogramming from single-cell transcriptomicsProceedings of the National Academy of Sciences · 2024 · DOI: 10.1073/pnas.2401540121
  7. 07Ligang Zhu and Jin WangQuantifying Landscape and Flux from Single-Cell Omics: Unraveling the Physical Mechanisms of Cell FunctionJACS Au · 2025 · DOI: 10.1021/jacsau.5c00620