High-definition spatial transcriptomics for in situ tissue profiling

Sanja Vickovic; Gökcen Eraslan; Fredrik Salmén; Johanna Klughammer; Linnea Stenbeck; Denis Schapiro; Tarmo Äijö; Richard Bonneau; Ludvig Bergenstråhle; José Fernandéz Navarro; Joshua Gould; Gabriel K Griffin; Åke Borg; Mostafa Ronaghi; Jonas Frisén; Joakim Lundeberg; Aviv Regev; Patrik L Ståhl

doi:10.1038/s41592-019-0548-y

High-definition spatial transcriptomics for in situ tissue profiling

Nat Methods. 2019 Oct;16(10):987-990. doi: 10.1038/s41592-019-0548-y. Epub 2019 Sep 9.

Authors

Sanja Vickovic^{1

2}, Gökcen Eraslan^#³, Fredrik Salmén^#⁴, Johanna Klughammer^#³, Linnea Stenbeck^#⁴, Denis Schapiro^{3

5}, Tarmo Äijö⁶, Richard Bonneau^{7

8}, Ludvig Bergenstråhle⁴, José Fernandéz Navarro⁴, Joshua Gould³, Gabriel K Griffin^{3

8}, Åke Borg⁹, Mostafa Ronaghi¹⁰, Jonas Frisén¹¹, Joakim Lundeberg^{12

13}, Aviv Regev^{3

14}, Patrik L Ståhl⁴

Affiliations

¹ Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. vickovic@broadinstitute.org.
² Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. vickovic@broadinstitute.org.
³ Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁴ Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
⁵ Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA, USA.
⁶ Center for Computational Biology, Flatiron Institute, New York, NY, USA.
⁷ Center for Data Science, New York University, New York, NY, USA.
⁸ Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
⁹ Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
¹⁰ Illumina, Inc., San Diego, CA, USA.
¹¹ Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
¹² Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Stockholm, Sweden. joakim.lundeberg@scilifelab.se.
¹³ Department of Bioengineering, Stanford University, Stanford, CA, USA. joakim.lundeberg@scilifelab.se.
¹⁴ Howard Hughes Medical Institute and Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.

^# Contributed equally.

Abstract

Spatial and molecular characteristics determine tissue function, yet high-resolution methods to capture both concurrently are lacking. Here, we developed high-definition spatial transcriptomics, which captures RNA from histological tissue sections on a dense, spatially barcoded bead array. Each experiment recovers several hundred thousand transcript-coupled spatial barcodes at 2-μm resolution, as demonstrated in mouse brain and primary breast cancer. This opens the way to high-resolution spatial analysis of cells and tissues.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms / pathology
Female
Gene Expression Profiling*
Humans
Mice
Olfactory Bulb / cytology
Sequence Analysis, RNA / methods
Single-Cell Analysis / methods
Tissue Array Analysis
Transcriptome*

Abstract

Publication types

MeSH terms

Grants and funding