Article

Visualization and analysis of gene expression in tissue sections by spatial transcriptomics

Patrik L. StåhlDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, SwedenFredrik SalménScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenSanja VickovićScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenAnna LundmarkDepartment of Dental Medicine, Division of Periodontology, Karolinska Institute, SE-141 04 Huddinge, SwedenJosé Fernández NavarroDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, SwedenJens P. MagnussonDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, SwedenStefania GiacomelloScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenMichaela AspScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenJakub Orzechowski WestholmScience for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Box 1031, SE-171 21 Solna, SwedenMikael HussScience for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Box 1031, SE-171 21 Solna, SwedenAnnelie MollbrinkScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenSten LinnarssonDivision of Molecular Neuroscience, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-17177 Stockholm, SwedenSimone CodeluppiDepartment of Physiology and Pharmacology, Karolinska Institute, SE-17177 Stockholm, SwedenÅke BorgDivision of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, SE-223 81 Lund, SwedenFredrik PonténDepartment of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, SwedenPaul Igor CosteaScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenPelin SahlénScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenJan MulderScience for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-171 77 Stockholm, SwedenOlaf BergmannDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, SwedenJoakim LundebergScience for Life Laboratory, Division of Gene Technology, KTH Royal Institute of Technology, SE-106 91 Stockholm, SwedenJonas FrisénDepartment of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden

2016en

ABI

Abstract

Analysis of the pattern of proteins or messengerRNAs (mRNAs) in histological tissue sections is a cornerstone in biomedical research and diagnostics. This typically involves the visualization of a few proteins or expressed genes at a time. We have devised a strategy, which we call "spatial transcriptomics," that allows visualization and quantitative analysis of the transcriptome with spatial resolution in individual tissue sections. By positioning histological sections on arrayed reverse transcription primers with unique positional barcodes, we demonstrate high-quality RNA-sequencing data with maintained two-dimensional positional information from the mouse brain and human breast cancer. Spatial transcriptomics provides quantitative gene expression data and visualization of the distribution of mRNAs within tissue sections and enables novel types of bioinformatics analyses, valuable in research and diagnostics.

Identifiers

DOI: 10.1126/science.aaf2403

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