Title: Genetically-encoded bioluminescence/fluorescence tools for multiscale imaging of cellular events in deep animal tissues

 

Takahiro KUCHIMARU

Division of Bioconvergence, Center for Molecular Imaging, Jichi Medical University

 

We have developed genetically-encoded bioluminescence/fluorescence tools for multiscale imaging of cellular events in deep animal tissues. Specifically, we have developed synthetic near-infrared bioluminescence reactions that surpass the natural reaction in sensitivity, enabling improved detection of targets in deep tissues (1-3). In addition, these near-infrared bioluminescence systems provide high temporal resolution, paving the way for molecular imaging modality of freely moving animals (4).

 Noninvasive bioluminescence imaging in animal models has strong potential in combination with single-cell genetic profiling of tissue-comprising cells. In particular, cell-cell interactions play pivotal roles in tissue homeostasis and disease progression. These days, spatial single-cell transcriptomics has emerged as a powerful approach to study cell-cell interactions in animal tissues. However, current methods—primarily based on computational inference or tissue section–based analyses—often involve trade-offs between sequencing depth and spatial resolution. To bridge this gap, we developed sGRAPHIC, a genetic tool for fluorescently labeling cell-cell interactions in living tissues and isolating labeled cells for single-cell transcriptomics (5). This optical labeling-based omics approach can be further enhanced by integration with multi-omics analysis beyond transcriptomics.

 

References

(1) Nat Commun 2016, 7, 11856 (2) Science 2018, 359, 935 (3) bioRxiv 2025.01.20.633992 (4) Int J Mol Sci 2024, 25, 7338. (5) Nat Commun 2023, 14, 8031