Understanding cell fate retention and transitions

Determine the biological and dynamical mechanisms by which cells retain established fates and transition between distinct cell fates during development, injury, and directed differentiation.

Background

The paper motivates the need to explain how robust, reproducible developmental trajectories arise from high-dimensional gene regulatory networks and signaling inputs. Despite abundant single-cell RNA-sequencing data, a comprehensive theoretical understanding of cell fate retention and transitions across contexts remains incomplete.

To address this gap, the authors introduce a phenomenological model that combines low-dimensional geometric landscapes with high-dimensional Hopfield-inspired dynamics to connect gene expression, signaling, and cell fate. Solving the open problem would clarify the mechanisms that enable stable cell identities and controlled transitions under developmental, injury, and directed differentiation conditions.