量化单细胞组学中的景观与通量:揭示细胞功能的物理机制
Quantifying Landscape and Flux from Single-Cell Omics: Unraveling the Physical Mechanisms of Cell Function.
作者信息
Zhu Ligang, Wang Jin
机构信息
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Department of Chemistry and Department of Physics and Astronomy, Stony Brook University, Stony Brook, New York 11794, United States.
出版信息
JACS Au. 2025 Aug 7;5(8):3738-3757. doi: 10.1021/jacsau.5c00620. eCollection 2025 Aug 25.
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.
单细胞测序技术的最新进展重塑了我们对细胞过程的理解。在生物学研究领域,从单细胞组学理解潜在的物理和化学机制是一个充满前景的前沿领域,但仍未得到充分探索。这一知识差距源于将非平衡物理和化学原理映射到细胞功能的异质和复杂动态过程中的复杂性。在此,我们强调了几个关键的生物学过程,以开启这一具有挑战性的旅程,即利用单细胞组学的力量来阐明各种生物细胞功能的非平衡物理和化学基础,包括细胞周期、细胞分化/重编程、癌症进展和转移以及胚胎动态发育。这一观点为细胞分裂和分化提供了突破性的见解,强调非平衡格局和通量是驱动细胞功能的力量,可通过单细胞组学数据进行量化,为细胞可塑性和命运决定提供了新的见解。此外,它还基于组学数据提供了癌症形成和转移的可能预警信号。深入探索动态发育的奇妙之处,它展示了从时间分辨的单细胞数据中由胚胎发生的动态格局-通量所决定的未被发现的非平衡物理化学机制。这一观点进一步展望了时空多组学与非平衡物理和化学理论整合所面临的挑战和机遇,以期更全面、深入地理解生命的众多过程。因此,这一观点总结了这一新兴领域的关键进展,并指出了充分整合单细胞生物技术和物理化学理论在生命科学中的潜力所面临的下一个机遇和挑战。