Slide-tags enables single-nucleus barcoding for multimodal spatial genomics

• 成果类型: Article
• 署名作者: Russell, Andrew J. C.; Weir, Jackson A.; Nadaf, Naeem M.; Shabet, Matthew; Kumar, Vipin; Kambhampati, Sandeep; Raichur, Ruth; Marrero, Giovanni J.; Liu, Sophia; Balderrama, Karol S.; Vanderburg, Charles R.; Shanmugam, Vignesh; Tian, Luyi; Iorgulescu, J. Bryan; Yoon, Charles H.; Wu, Catherine J.; Macosko, Evan Z.; Chen, Fei
• 署名单位: Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University; Harvard University; Harvard University; Massachusetts Institute of Technology (MIT); Harvard University; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Harvard University; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Guangzhou Laboratory; University of Texas System; UTMD Anderson Cancer Center
• 刊物名称: Nature
• ISSN/ISSBN: 0028-5631
• DOI: 10.1038/s41586-023-06837-4
• 发表日期: 2024-01-04
• 关键词: cytidine deaminase aid; gene-expression; wide expression; cell; seq; accessibility; melanoma; light; state; dark

摘要

Recent technological innovations have enabled the high-throughput quantification of gene expression and epigenetic regulation within individual cells, transforming our understanding of how complex tissues are constructed1-6. However, missing from these measurements is the ability to routinely and easily spatially localize these profiled cells. We developed a strategy, Slide-tags, in which single nuclei within an intact tissue section are tagged with spatial barcode oligonucleotides derived from DNA-barcoded beads with known positions. These tagged nuclei can then be used as an input into a wide variety of single-nucleus profiling assays. Application of Slide-tags to the mouse hippocampus positioned nuclei at less than 10 mu m spatial resolution and delivered whole-transcriptome data that are indistinguishable in quality from ordinary single-nucleus RNA-sequencing data. 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 contextualized receptor-ligand interactions driving B cell maturation in lymphoid tissue. A major benefit of Slide-tags is that it is easily adaptable to almost any single-cell measurement technology. As a proof of principle, we performed multiomic measurements of open chromatin, RNA and T cell receptor (TCR) sequences in the same cells from metastatic melanoma, identifying transcription factor motifs driving cancer cell state transitions in spatially distinct microenvironments. Slide-tags offers a universal platform for importing the compendium of established single-cell measurements into the spatial genomics repertoire. Slide-tags enables multiomic sequencing of single cells and their localization within tissues.