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Science Papers on Way to Track Interactions of Single Cells, Spatially Resolved Single-Cell RNA Sequencing

A technique that combines viral barcoding with sequencing to track interactions between individual nervous system cells during inflammation is reported in this week's Science. Called RABID-seq — short for rabies barcode interaction detection followed by sequencing — the method is based on a glycoprotein G-deficient pseudotyped rabies virus engineered to express a unique fluorescent mRNA barcode that can be analyzed by single-cell RNA sequencing. In the study, RABID-seq's developers at Harvard Medical School use it to study microglia-astrocyte communication in the context of central nervous system inflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. Among their findings are signaling pathways controlled by specific axon guidance molecules that act as mediators of microglia-astrocyte interactions and which could potentially be targets for therapeutic intervention.

A workflow for spatially resolved single-cell RNA sequencing (scRNA-seq) is presented in Science Advances this week. While scRNA-seq can profile the transcriptomes of thousands of cells in a single experiment, it does not provide information on the spatial organization of cells. To address this, a team led by investigators from the University of California, San Francisco, developed XYZeq, a method that uses two rounds of split-pool indexing to encode the spatial location of each cell from a tissue sample into combinatorially indexed scRNA-seq libraries. The researchers demonstrate XYZeq by using it to profile mouse tumor models to capture spatially barcoded transcriptomes from tens of thousands of cells. "XYZeq provides a scalable workflow that can be adapted to multiple z-layers of tissue and can potentially facilitate analysis of entire organs," the authors write. "Large-scale integrated profiling of multiple modalities of single cells mapped to the structural features of their tissue will enable greater understanding of how the tissue microenvironment affects cellular infiltration and interaction in health and disease."