High-Spatial-Resolution Multi-Omics Sequencing via Deterministic Barcoding in Tissue

We present deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via next-generation sequencing (NGS). Parallel microfluidic channels were used to deliver DNA barcodes to the surface of a tissue slide, and...

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Bibliographic Details
Published in:Cell 2020-12, Vol.183 (6), p.1665-1681.e18
Main Authors: Liu, Yang, Yang, Mingyu, Deng, Yanxiang, Su, Graham, Enninful, Archibald, Guo, Cindy C., Tebaldi, Toma, Zhang, Di, Kim, Dongjoo, Bai, Zhiliang, Norris, Eileen, Pan, Alisia, Li, Jiatong, Xiao, Yang, Halene, Stephanie, Fan, Rong
Format: Article
Language:English
Subjects:
high spatial resolution
in situ barcoding
mouse embryo
next-generation sequencing
spatial multi-omics
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Summary:We present deterministic barcoding in tissue for spatial omics sequencing (DBiT-seq) for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via next-generation sequencing (NGS). Parallel microfluidic channels were used to deliver DNA barcodes to the surface of a tissue slide, and crossflow of two sets of barcodes, A1-50 and B1-50, followed by ligation in situ, yielded a 2D mosaic of tissue pixels, each containing a unique full barcode AB. Application to mouse embryos revealed major tissue types in early organogenesis as well as fine features like microvasculature in a brain and pigmented epithelium in an eye field. Gene expression profiles in 10-μm pixels conformed into the clusters of single-cell transcriptomes, allowing for rapid identification of cell types and spatial distributions. DBiT-seq can be adopted by researchers with no experience in microfluidics and may find applications in a range of fields including developmental biology, cancer biology, neuroscience, and clinical pathology. [Display omitted] •Deterministic barcoding in tissue enables NGS-based spatial multi-omics mapping•DBiT-seq identified spatial patterning of major tissue types in mouse embryos•Revealed retinal pigmented epithelium and microvascular endothelium at cellular level•Direct integration with scRNA-seq data allows for rapid cell type identification DBiT-seq is a microfluidic-based method to deliver barcodes to the surface of a tissue slide to allow for spatial omics sequencing with 10-μm pixel size.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2020.10.026