All-optical multimodal mapping of single-cell-type-specific metabolic activities via REDCAT
Abstract Metabolism is fundamental to cell function, yet its activities vary across tissue environments. Resolving these processes in situ at single-cell resolution is crucial for understanding physiology in health and disease. However, existing methods lack biochemical specificity or direct linkage to cell identity. Here we report a method, Raman Enhanced Delineation of Cell Atlases in Tissues (REDCAT), an all-optical platform integrating Raman scattering microscopy and high-plex immunofluorescence to co-map metabolism and cell types. REDCAT achieves subcellular profiling of protein, lipid, nuclear metabolites and redox metabolism in human tissues. In lymph nodes, it revealed cell-type-specific metabolic specialization. In lymphoma, REDCAT uncovered profound reprogramming and transitional states during tumor transformation. In the liver, it resolved zonation-dependent metabolic gradients. By linking cell identity to spatial metabolic states, REDCAT provides a framework for studying immunity and cancer, offering a path to deciphering the metabolic basis of disease.
Authors
- Negin Farzad (ORCID: https://orcid.org/0009-0002-5391-9363)
- Presha Rajbhandari (ORCID: https://orcid.org/0000-0003-2184-7238)
- Rong Fan (ORCID: https://orcid.org/0000-0001-7805-8059)
- Nancy R. Zhang (ORCID: https://orcid.org/0000-0002-0880-5749)
- Zhiliang Bai (ORCID: https://orcid.org/0000-0002-3977-3057)
- Jungmin Nam (ORCID: https://orcid.org/0000-0002-6717-1328)
- Lingyan Shi (ORCID: https://orcid.org/0000-0003-1373-3206)
- Brent R. Stockwell (ORCID: https://orcid.org/0000-0002-3532-3868)
- Archibald Enninful (ORCID: https://orcid.org/0000-0002-6350-6530)
- Anthony A. Fung (ORCID: https://orcid.org/0000-0003-1631-7451)
- Mina L. Xu (ORCID: https://orcid.org/0000-0001-9513-245X)
- Zhaojun Zhang (ORCID: https://orcid.org/0000-0001-6518-0207)
- Zongming Ma (ORCID: https://orcid.org/0000-0003-2401-0177)
- Yajuan Li (ORCID: https://orcid.org/0000-0003-2328-6956)
- Xiaoyu Qin
- Hongje Jang
- Jorge Villazon
- Hua Tian
Institutions
- Pennsylvania Department of Health (US)
- Columbia University Irving Medical Center (US)
- Yale Cancer Center (US)
- Yale University (US)
- University of California San Diego (US)
- Children's Institute of Pittsburgh (US)
- La Jolla Bioengineering Institute (US)
- Columbia University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Methods
- Published
- 2026-08-27
- DOI
- https://doi.org/10.1038/s41592-026-03180-0
- Citations
- 6
- Primary Topic
- Advanced Biosensing Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 15.16
Funders
- National Institutes of Health