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SpaceBar enables clone tracing in spatial transcriptomic data

Kinsler, G.; Fagan, C.; Li, H.; Kaster, J.; Dunne, M.; Vander Velde, R. J.; Boe, R. H.; Shaffer, S.; Herlyn, M.; Raj, A.; Heyman, Y.

2025-02-14 genomics
10.1101/2025.02.10.637514 bioRxiv
Show abstract

We report a cellular barcoding strategy, SpaceBar, that enables simultaneous clone tracing and spatial transcriptomics profiling. Our approach uses a library of 96 synthetic barcode sequences that can be robustly detected by imaging based spatial transcriptomics (seqFISH), delivered such that each cell is labeled with a combination of barcodes. We used these barcodes to label melanoma cells in a tumor xenograft model and profiled both clone identity and spatial gene expression in situ. We developed a gene scoring metric that quantifies how strongly gene expression is driven by intrinsic cellular cues or extrinsic environmental signals. Our framework distinguishes between clonal dynamics and environmentally-driven transcriptional regulation in complex tissue contexts.

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