Slide-tags enables single-nucleus barcoding for multimodal spatial genomics
© 2023. The Author(s)..
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.
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:625 |
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| Enthalten in: |
Nature - 625(2024), 7993 vom: 07. Jan., Seite 101-109 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Russell, Andrew J C [VerfasserIn] |
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| Links: |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 19.01.2024 Date Revised 10.02.2024 published: Print-Electronic UpdateOf: bioRxiv. 2023 Apr 03;:. - PMID 37066158 Citation Status MEDLINE |
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| doi: |
10.1038/s41586-023-06837-4 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365837105 |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a 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 | ||
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| 700 | 1 | |a Nadaf, Naeem M |e verfasserin |4 aut | |
| 700 | 1 | |a Shabet, Matthew |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Vipin |e verfasserin |4 aut | |
| 700 | 1 | |a Kambhampati, Sandeep |e verfasserin |4 aut | |
| 700 | 1 | |a Raichur, Ruth |e verfasserin |4 aut | |
| 700 | 1 | |a Marrero, Giovanni J |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Sophia |e verfasserin |4 aut | |
| 700 | 1 | |a Balderrama, Karol S |e verfasserin |4 aut | |
| 700 | 1 | |a Vanderburg, Charles R |e verfasserin |4 aut | |
| 700 | 1 | |a Shanmugam, Vignesh |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Luyi |e verfasserin |4 aut | |
| 700 | 1 | |a Iorgulescu, J Bryan |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Charles H |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Catherine J |e verfasserin |4 aut | |
| 700 | 1 | |a Macosko, Evan Z |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Fei |e verfasserin |4 aut | |
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