RT Journal Article SR Electronic T1 Slide-seq: A Scalable Technology for Measuring Genome-Wide Expression at High Spatial Resolution JF bioRxiv FD Cold Spring Harbor Laboratory SP 563395 DO 10.1101/563395 A1 Samuel G. Rodriques A1 Robert R. Stickels A1 Aleksandrina Goeva A1 Carly A. Martin A1 Evan Murray A1 Charles R. Vanderburg A1 Joshua Welch A1 Linlin M. Chen A1 Fei Chen A1 Evan Z. Macosko YR 2019 UL http://biorxiv.org/content/early/2019/02/28/563395.abstract AB The spatial organization of cells in tissue has a profound influence on their function, yet a high-throughput, genome-wide readout of gene expression with cellular resolution is lacking. Here, we introduce Slide-seq, a highly scalable method that enables facile generation of large volumes of unbiased spatial transcriptomes with 10 µm spatial resolution, comparable to the size of individual cells. In Slide-seq, RNA is transferred from freshly frozen tissue sections onto a surface covered in DNA-barcoded beads with known positions, allowing the spatial locations of the RNA to be inferred by sequencing. To demonstrate Slide-seq’s utility, we localized cell types identified by large-scale scRNA-seq datasets within the cerebellum and hippocampus. We next systematically characterized spatial gene expression patterns in the Purkinje layer of mouse cerebellum, identifying new axes of variation across Purkinje cell compartments. Finally, we used Slide-seq to define the temporal evolution of cell-type-specific responses in a mouse model of traumatic brain injury. Slide-seq will accelerate biological discovery by enabling routine, high-resolution spatial mapping of gene expression.One Sentence Summary Slide-seq measures genome-wide expression in complex tissues at 10-micron resolution.