Genome-wide spatial expression profiling in formalin-fixed tissues

Gracia Villacampa, Eva; Larsson, Ludvig; Mirzazadeh, Reza; Kvastad, Linda; Andersson, Alma; Mollbrink, Annelie; Kokaraki, Georgia; Monteil, Vanessa; Schultz, Niklas; Appelberg, Karin Sofia; Montserrat, Nuria; Zhang, Haibo; Penninger, Josef M.; Miesbach, Wolfgang; Mirazimi, Ali; Carlson, Joseph; Lundeberg, Joakim

doi:10.1016/j.xgen.2021.100065

Cited by 132Single-cell and spatial transcriptomicsGene expression and cancer classificationMolecular Biology Techniques and Applications

Genome-wide spatial expression profiling in formalin-fixed tissues

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Gracia Villacampa, Eva, Larsson, Ludvig, Mirzazadeh, Reza, Kvastad, Linda, Andersson, Alma, Mollbrink, Annelie, Kokaraki, Georgia, Monteil, Vanessa +9 more·2021·Cell Genomics

DOI 10.1016/j.xgen.2021.100065PMC PMC9903805

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Abstract

Formalin-fixed paraffin embedding (FFPE) is the most widespread long-term tissue preservation approach. Here, we report a procedure to perform genome-wide spatial analysis of mRNA in FFPE-fixed tissue sections, using well-established, commercially available methods for imaging and spatial barcoding using slides spotted with barcoded oligo(dT) probes to capture the 3' end of mRNA molecules in tissue sections. We applied this method for expression profiling and cell type mapping in coronal sections from the mouse brain to demonstrate the method's capability to delineate anatomical regions from a molecular perspective. We also profiled the spatial composition of transcriptomic signatures in two ovarian carcinosarcoma samples, exemplifying the method's potential to elucidate molecular mechanisms in heterogeneous clinical samples. Finally, we demonstrate the applicability of the assay to characterize human lung and kidney organoids and a human lung biopsy specimen infected with SARS-CoV-2. We anticipate that genome-wide spatial gene expression profiling in FFPE biospecimens will be used for retrospective analysis of biobank samples, which will facilitate longitudinal studies of biological processes and biomarker discovery.

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Visium allows retrospective analysis of stored FFPE blocks.
“An important advantage of this methodology is the possibility for retrospective analysis of stored FFPE blocks55, which allows designing experiments around a desired age range.”
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Authors: Gracia Villacampa, E., Larsson, L., Mirzazadeh, R., Kvastad, L., Andersson, A., Mollbrink, A., Kokaraki, G., Monteil, V., Schultz, N., Appelberg, K. S., Montserrat, N., Zhang, H., Penninger, J. M., Miesbach, W., Mirazimi, A., Carlson, J., & Lundeberg, J.
Affiliations: Science for Life Laboratory (SE)
Karolinska Institutet (SE)
Karolinska University Hospital (SE)
Public Health Agency of Sweden (SE)
University of Toronto (CA)
Institute of Molecular Biotechnology (AT)
University Hospital Frankfurt (DE)
Corresponding author: Lundeberg, Joakim
ORCID: Gracia Villacampa, Eva
Larsson, Ludvig
Mirzazadeh, Reza
Kvastad, Linda
Andersson, Alma
Mollbrink, Annelie
Kokaraki, Georgia
Monteil, Vanessa
Zhang, Haibo
Penninger, Josef M.
Miesbach, Wolfgang
Carlson, Joseph
Lundeberg, Joakim
Venue: Cell Genomics
Publisher: Elsevier BV
Published: 2021-12
Volume: 1
Issue: 3
Pages: 100065
ISSN: 2666-979X (ISSN-L)
DOI: 10.1016/j.xgen.2021.100065
PMC: PMC9903805
OpenAlex: W4200565305
Cited by: 132
References: 11
Citations by year: 2026: 16 · 2025: 27 · 2024: 30 · 2023: 27 · 2022: 17 · 2021: 13 · 2020: 2
FWCI: 6.91
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cell Genomics (publishedVersion, cc-by)
bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Swedish Cancer Society
Swedish Research Council
H2020 (874741)
Science for Life Laboratory
Erling Persson Family Foundation
Knut och Alice Wallenbergs Stiftelse (2018.0172)
Stiftelsen för Strategisk Forskning
Horizon 2020 (824110 EASI-Genomics, 874656 discovAIR)
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, formalin-fixed paraffin-embedded tissue, cell type mapping, ovarian carcinosarcoma, lung organoids, kidney organoids, COVID-19 pandemic, lung biopsy, biomarker discovery

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Genome-wide spatial expression profiling in formalin-fixed tissues

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