Mapping Cell Fate Transition in Space and Time

Yichen Gu, Jialin Liu, Chen Li, Joshua D. Welch

Abstract: Cell fate transition is fundamentally a spatiotemporal process, but previous work has largely neglected the spatial dimension. Incorporating both space and time into models of cell fate transition would be a key step toward characterizing how interactions among neighboring cells, the presence of local niche factors, and physical migration of cells contribute to tissue development. To realize this potential, we propose a model for jointly inferring spatial and temporal dynamics of cell fate transition from spatial transcriptomic data. Our approach extends the RNA velocity framework to model single-cell gene expression dynamics of an entire tissue with spatially coupled differential equations. Our principled probabilistic approach enables the incorporation of time point labels and multiple slices. We further introduce the idea of cell velocity, which is defined as the physical direction of cell maturation and migration. Simulated data analysis indicates that incorporating spatial coordinates significantly improves the accuracy of velocity and time inference. Our work introduces a new dimension into the study of cell fate transitions and lays a foundation for modeling the collective dynamics of cells comprising an entire tissue. The full paper is at https://www.biorxiv.org/content/10.1101/2024.02.12.579941v1.