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We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are \u2018tagged\u2019 with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 micron spatial resolution, and delivered whole-transcriptome data that was indistinguishable in quality from ordinary snRNA-seq. To demonstrate that Slide-tags can be applied to a wide variety of human tissues, we performed the assay on brain, tonsil, and melanoma. We revealed cell-type-specific spatially varying gene expression across cortical layers and spatially contextualised receptor-ligand interactions driving B-cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to virtually any single-cell measurement technology. As proof of principle, we performed multiomic measurements of open chromatin, RNA, and T-cell receptor sequences in the same cells from metastatic melanoma. We identified spatially distinct tumour subpopulations to be differentially infiltrated by an expanded T-cell clone and undergoing cell state transition driven by spatially clustered accessible transcription factor motifs. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire.<\/jats:p>","DOI":"10.1101\/2023.04.01.535228","type":"posted-content","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T20:05:30Z","timestamp":1680552330000},"source":"Crossref","is-referenced-by-count":16,"title":["Slide-tags: scalable, single-nucleus barcoding for multi-modal spatial genomics"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5411-2807","authenticated-orcid":false,"given":"Andrew J. 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