Spatial transcriptomics is a technology used to spatially resolve RNA-seq data, and thereby all mRNAs, in individual tissue sections. The ordered attachment of spatially barcoded reverse transcription oligo primers to the surface of microscope slides enables the encoding and maintenance of positional information throughout mRNA sample processing and subsequent sequencing. This contrasts with RNA-sequencing of single cells, or the sequencing of bulk RNA extracted from tissue volumes, where precise spatial information is lost
Method
When a tissue cryosection is attached to a spatial transcriptomic slide the barcoded primers bind and capture adjacent mRNAs from the tissue. While the tissue section is attached to the slide, reverse transcription of captured mRNA is initiated and the resulting cDNA incorporates the spatial barcode of the primer. Following mRNA capture and reverse transcription, sequencing libraries are prepared and analyzed with Illumina dye sequencing. The spatial barcode present within each generated sequence allows the data for each individual mRNA transcript to be mapped back to its point of origin within the tissue section.
History
Spatial transcriptomics was invented and developed in 2016 by Jonas Frisén, Joakim Lundeberg, Patrik Ståhl and their colleagues in Stockholm, Sweden. In 2019 at the Broad Institute, the labs of Fei Chen and Evan Macosko developed Slide-seq, which used barcoded oligos on beads.
Publications using spatial transcriptomics (as of April 2018)
Stahl, P. L., F. Salmen, S. Vickovic, A. Lundmark, J. F. Navarro, J. Magnusson, S. Giacomello, M. Asp, J. O. Westholm, M. Huss, A. Mollbrink, S. Linnarsson, S. Codeluppi, A. Borg, F. Ponten, P. I. Costea, P. Sahlen, J. Mulder, O. Bergmann, J. Lundeberg, and J. Frisen. "Visualization and Analysis of Gene Expression in Tissue Sections by Spatial Transcriptomics." Science 353, no. 6294 : 78-82..
Giacomello, Stefania, Fredrik Salmén, Barbara K. Terebieniec, Sanja Vickovic, José Fernandez Navarro, Andrey Alexeyenko, Johan Reimegård, Lauren S. Mckee, Chanaka Mannapperuma, Vincent Bulone, Patrik L. Ståhl, Jens F. Sundström, Nathaniel R. Street, and Joakim Lundeberg. "Spatially Resolved Transcriptome Profiling in Model Plant Species." Nature Plants 3, no. 6 : 17061..
Asp, Michaela, Fredrik Salmén, Patrik L. Ståhl, Sanja Vickovic, Ulrika Felldin, Marie Löfling, José Fernandez Navarro, Jonas Maaskola, Maria J. Eriksson, Bengt Persson, Matthias Corbascio, Hans Persson, Cecilia Linde, and Joakim Lundeberg. "Spatial Detection of Fetal Marker Genes Expressed at Low Level in Adult Human Heart Tissue." Scientific Reports 7, no. 1..
Berglund E, Maaskola J, Schultz N, et al. "Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity." Nat Commun 2018;9:2419..
Moncada, Reuben, Florian Wagner, Marta Chiodin, Joseph C. Devlin, Maayan Baron, Cristina H. Hajdu, Diane Simeone, and Itai Yanai. "Building a Tumor Atlas: Integrating Single-cell RNA-Seq Data with Spatial Transcriptomics in Pancreatic Ductal Adenocarcinoma." 2018..
Rodriques, S. G., Stickels, R. R., Goeva, A., Martin, C. A., Murray, E., Vanderburg, C. R., … Macosko, E. Z.. Slide-seq: A scalable technology for measuring genome-wide expression at high spatial resolution. Science, 363, 1463–1467.
