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  • Perspective
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Temporal and spatial omics technologies for 4D profiling

Nature Methods volume 22, pages 1408–1419 (2025)Cite this article

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Abstract

Cells have distinct molecular repertoires on their surfaces and unique intracellular biomolecular profiles that play pivotal roles in orchestrating a myriad of biological responses in the context of growth, development and disease. A persistent challenge in the deep exploration of these cues has been in our inability to effectively and precisely capture the temporal and spatial characteristics of living cells. In this Perspective, we delve into techniques for temporal and two- and three-dimensional spatial omics analyses and underscore how their harmonious fusion promises to unlock insights into the dynamics and diversity of individual cells within biological systems such as tissues and organoids. We then explore four-dimensional profiling, a nascent but promising frontier that adds a temporal (fourth-dimension) component to three-dimensional omics; highlight the advancements, challenges and gaps in the field; and discuss potential strategies for further technological development.

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Fig. 1: Timeline depicting the evolution of temporal and spatial omics.
Fig. 2: Spatiotemporal profiling.
Fig. 3
Fig. 4: Future approaches for 4D profiling.

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Acknowledgements

This work was supported by the NSF Graduate Research Fellowship Program to D.E.R. and National Institutes of Health award R00CA256353 to J.K.

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Authors and Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA

    David E. Reynolds, Daniel Oh, Phoebe Vallapureddy & Jina Ko

  2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Yoon Ho Roh & Jina Ko

  3. Department of Energy and Chemical Engineering, Incheon National University, Incheon, Republic of Korea

    Yoon Ho Roh

  4. Department of Biomedical Engineering, Yale University, New Haven, CT, USA

    Rong Fan

  5. Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA

    Rong Fan

  6. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

    Rong Fan

  7. Human and Translational Immunology Program, Yale School of Medicine, New Haven, CT, USA

    Rong Fan

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Contributions

D.E.R. led the writing and editing of the paper and created the figures. Y.H.R., D.O. and P.V. contributed to the writing and editing. R.F. provided feedback and assisted with revisions. J.K. supervised and reviewed the manuscript.

Corresponding author

Correspondence to Jina Ko.

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Competing interests

R.F. is a scientific founder and adviser for IsoPlexis, Singleron Biotechnologies and AtlasXomics. J.K. is a scientific cofounder and adviser for Aperture Bio. The remaining authors declare no competing interests.

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Nature Methods thanks Guangdun Peng and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Madhura Mukhopadhyay, in collaboration with the Nature Methods team.

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Reynolds, D.E., Roh, Y.H., Oh, D. et al. Temporal and spatial omics technologies for 4D profiling. Nat Methods 22, 1408–1419 (2025). https://doi.org/10.1038/s41592-025-02683-6

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