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

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2020 Nov 14

PMID 33188776

Citations 329

Authors

Yang Liu

Mingyu Yang

Yanxiang Deng

Graham Su

Archibald Enninful

Cindy C Guo

Toma Tebaldi

Di Zhang

Dongjoo Kim

Zhiliang Bai

Eileen Norris

Alisia Pan

Jiatong Li

Yang Xiao

Stephanie Halene

Rong Fan

Affiliations

Soon will be listed here.

Abstract

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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