Decoding cell fate: integrated experimental and computational analysis at the single-cell level.

Abstract

Understanding cell fate determination is crucial in developmental biology and regenerative medicine. Although theoretical frameworks such as epigenetic landscape and gene regulatory networks have been proposed for decades, traditional studies have often been limited by population-averaging and low-throughput techniques, which obscure the heterogeneity of individual cells and fail to provide a systematic view of cell fate control. Recent advances in single-cell technologies have provided unprecedented resolution, revealing the complexity of cell fate decisions and driving the need for more sophisticated computational methods. In this review, we first emphasize experimental advances, such as single-cell multi-omics, lineage tracing, and perturbation techniques, which produce novel data modalities and enable dynamic tracking of cell fate transitions. We then discuss the modeling paradigms for cell fate studies and further assess the role of emerging AI tools in perturbation modeling and discuss the potential of single-cell and spatial foundation models. Additionally, we highlight several case studies on predicting and manipulating cell fates, and discuss key challenges and future directions of the field. This work generates no new software.