Single Cell Multiome and Spatial Transcriptomics Analysis for Next Generation Molecular Profiling

Next generation genomic technologies such as RNA-seq, and in particular single cell RNA-seq, significantly advanced our understanding of biology in health and disease, transforming our observation from bulk cells in a tissue to single cell resolution. Recent advances now enable single cell multiomic solutions, such as analysis of full length paired B-cell or T-cell receptors, surface protein expression, antigen specificity and gene expression in the same cell, as well as simultaneously profiling gene expression and open chromatin from the same cell, providing insights into cell types and states and gene regulatory mechanisms. Nonetheless, although single cell genomic technologies provide greater understanding of tissue complexity, they still lack spatial information. Spatial transcritomics, ‘omics on a tissue’, allows assigning cell types to their location in the tissue, enabling to elucidate cell heterogeneity and define cell types while also retaining spatial information. We have utilized the Visium spatial transcriptomics technology (10x genomics), using fresh frozen or FFPE samples, to study the immune crosstalk within lymph nodes to infection and explore the spatial organization of a mouse tumor model. We further developed an analytical pipeline for multi-resolution deconvolution of spatial transcriptomics profiles. These advances in spatial transcriptomics open the way for studying important determinants of cellular function by enabling a transcriptome-wide evaluation of gene expression in situ.