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High-Spatial-Resolution Multi-Omics Atlas Sequencing of Mouse Embryos via Deterministic Barcoding in Tissue

By 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

Posted 01 Oct 2019
bioRxiv DOI: 10.1101/788992

We present DBiT-seq –Deterministic Barcoding in Tissue for spatial omics sequencing – for co-mapping of mRNAs and proteins in a formaldehyde-fixed tissue slide via NGS sequencing. 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 10μm 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. In Brief Microfluidic deterministic barcoding of mRNAs and proteins in tissue slides followed by high-throughput sequencing enables the construction of a high-spatial-resolution multi-omics atlas at the genome scale. Application to mouse embryos (E10-12) identified major tissue types in early organogenesis and revealed fine tissue features such as retinal pigmented epithelium and endothelial microvasculature at the cellular level. ![Figure][1]</img> ### Competing Interest Statement R.F. is cofounder and scientific advisor of, and hold equity in, IsoPlexis and Singleron Biotechnologies with financial interest. [1]: pending:yes

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