High-definition spatial transcriptomics for in situ tissue profiling
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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. A dense, spatially barcoded bead array captures RNA from histological tissue sections for spatially resolved gene expression analysis.
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The lack of single-cell resolution with ST and the low sensitivity of ISS requires further technological improvements.
“While the technologies used here do not require harsh dissociation procedures like single-cell or single-nuclei approaches and maintain spatial information, the lack of single-cell resolution with ST and the low sensitivity of ISS requires further technological improvements (Eng et al. , 2019; Rodriques et al. , 2019; Vickovic et al. , 2019; Stickels et al. , 2020).”
From Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer’s Disease (2020) · cites this paper as Vickovic et al., 2019
Linkage of genome-wide transcriptomic information with spatial context is now possible with spatial transcriptomics, allowing on-slide RNA-sequencing of tissue sections at increasing resolution.
“In addition, linkage of genome-wide transcriptomic information with spatial context is now possible, with the advent of spatial transcriptomics, allowing ‘on-slide’ RNA-sequencing of tissue sections at ever-increasing resolution as the technologies in this area advance and mature.167”
From Understanding the cellular interactome of non-alcoholic fatty liver disease (2022) · cites this paper as [167]
PET imaging of collagen and molecular imaging of fibrosis allow fast, non-invasive, whole-organ quantitative and longitudinal readouts of drug efficacy in antifibrotic clinical trials.
“PET imaging of collagen and molecular imaging of fibrosis185,186, which allows fast, non-invasive, and whole-organ-quantitative and longitudinal readouts of drug efficacy in antifibrotic clinical trials”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [186]
The distribution of specific markers (Pcp4 and Slc17a7) captured by Stereo-seq exhibited the expected similarity to in situ hybridization data from Allen Brain Atlas and clearer patterns than HDST or Slide-seqV2-resolved expression data.
“The distribution of specific markers ( Pcp4 and Slc17a7 ) captured by Stereo-seq exhibited the expected similarity to in situ hybridization (ISH) data taken from Allen Brain Atlas (ABA) (Lein et al., 2007) and clearer patterns than HDST (Vickovic et al., 2019) or Slide-seqV2-resolved (Stickels et al., 2021) expression data (Figure S1E).”
From Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays (2022) · cites this paper as Vickovic et al., 2019
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- Authors
- Vickovic, S., Eraslan, G., Salmén, F., Klughammer, J., Stenbeck, L., Schapiro, D., Äijö, T., Bonneau, R., Bergenstråhle, L., Navarro, J. F., Gould, J., Griffin, G. K., Borg, Å., Ronaghi, M., Frisén, J., Lundeberg, J., Regev, A., & Ståhl, P. L.
- Affiliations
- Science for Life Laboratory (SE)
- Broad Institute (US)
- Flatiron Institute (US)
- Brigham and Women's Hospital (US)
- Lund University (SE)
- Illumina (United States) (US)
- Karolinska Institutet (SE)
- Corresponding author
- Lundeberg, Joakim
- ORCID
- Venue
- Nature Methods
- Published
- 2019-09-09
- Volume
- 16
- Issue
- 10
- Pages
- 987-990
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC6765407
- OpenAlex
- W2972983657
- Cited by
- 1,150
- References
- 34
- Citations by year
- 2026: 138 · 2025: 160 · 2024: 198 · 2023: 174 · 2022: 176 · 2021: 194 · 2020: 92 · 2019: 13 · 2018: 1 · 2017: 2
- FWCI
- 39.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Methods (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Knut och Alice Wallenbergs Stiftelse (2016.0454)
- Cancerfonden
- Stiftelsen för Strategisk Forskning
- Vetenskapsrådet
- European Molecular Biology Organization (ALTF 738-2017)
- Howard Hughes Medical Institute
- Klarman Family Foundation
- U.S. Department of Health & Human Services | National Institutes of Health (1OT2OD026673-1)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2ZHP3_181475)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Molecular Biology Techniques and Applications
- Keywords
- spatial transcriptomics, mouse brain, breast cancer, single-cell spatial analysis
- MeSH terms
- Animals, Breast Neoplasms, Female, Humans, Olfactory Bulb, Sequence Analysis, RNA, Gene Expression Profiling, Tissue Array Analysis, Mice, Single-Cell Analysis, Transcriptome
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