Quantifying Landscape and Flux from Single-Cell Omics: Unraveling the Physical Mechanisms of Cell Function

Recent advancements in single-cell sequencing technology have reshaped our understanding of cellular processes. While in the realm of biological research, the understanding of the underlying physical and chemical mechanisms from single-cell omics stands as a promising frontier, yet it is still not quite adequately explored. This knowledge gap stems from the complexities of mapping nonequilibrium physical and chemical principles onto the heterogeneous and complex dynamics of cellular functions. Herein, several key biological processes are highlighted to embark on this challenging journey of harnessing the power of single-cell omics to elucidate the nonequilibrium physical and chemical basis of various biological cell functions, including cell cycle, cell differentiation/reprogramming, cancer progression and metastasis, and embryonic dynamic development. This perspective presents breakthrough insights into cell division and differentiation, highlighting the nonequilibrium landscape and flux as the driving forces governing the cellular function which can be quantified through the single-cell omics data, providing new insights into cellular plasticity and fate determination. In addition, it provides possible early warning signals of cancer formation and metastasis based on omics data. Venturing into the wonders of dynamical development, it shows the uncovered nonequilibrium physicochemical mechanisms determined by the dynamical landscape-flux of embryogenesis from time-resolved single-cell data. This perspective further offers an outlook on challenges and opportunities for the integrations of spatiotemporal multiomics and nonequilibrium physical and chemical theories, in anticipation of a more comprehensive and in-depth understanding of the myriad processes of life. Hence, this perspective summarizes key advances in this emerging field and points to the next opportunities and challenges to fully integrate the potential of single-cell biotechnology and physical chemistry theory in life science.