[PDF][PDF] High-spatial-resolution multi-omics sequencing via deterministic barcoding in tissue

Y Liu, M Yang, Y Deng, G Su, A Enninful, CC Guo… - Cell, 2020 - cell.com
Y Liu, M Yang, Y Deng, G Su, A Enninful, CC Guo, T Tebaldi, D Zhang, D Kim, Z Bai
Cell, 2020cell.com
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 …
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.
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