학술논문
Slide-tags enables single-nucleus barcoding for multimodal spatial genomics
Document Type
Original Paper
Author
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
Source
Nature: International weekly journal of science. 625(7993):101-109
Subject
Language
English
ISSN
0028-0836
1476-4687
1476-4687
Abstract
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 μm 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.
Slide-tags enables multiomic sequencing of single cells and their localization within tissues.