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bioRxiv · 10.64898/2026.03.15.711134

A Unified Dynamical-Systems and Control-Theoretic Model for Single-Cell Fate Dynamics

Redd, D. M.·Green, S. G.·Terooatea, T. W.
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Abstract

Single-cell technologies now resolve cell-fate transitions, yet most analyses remain descriptive rather than predictive. This model unifies pseudotime (geometry), RNA velocity (local direction), optimal transport (OT; distributional evolution) and Schrodinger-bridge approaches (stochastic trajectories) within a stochastic dynamical-systems and control lens under partial observability1,2,3,4. We provide a minimal bridge from Chemical Master Equation models to SDE/Fokker-Planck descriptions and quasi-potentials, clarify what can and cannot be identified from snapshot data, and outline practical experimental design (time points, modalities, perturbations)5,6,7. We summarize method-specific assumptions, strengths and failure modes; present case studies (iPSC reprogramming, pancreas endocrinogenesis, hematopoiesis at scale); and detail a 10-step workflow with uncertainty propagation and reporting standards3,8,9. Finally, we recast intervention as a control problem: the realistic objective is probabilistic programmability-shifting terminal fate distributions with minimal inputs and preserved viability-rather than deterministic state-to-state command10.

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Redd, D. M., Green, S. G., Terooatea, T. W.. 2026-03-18. A Unified Dynamical-Systems and Control-Theoretic Model for Single-Cell Fate Dynamics. https://doi.org/10.64898/2026.03.15.711134

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