Cited by 321Single-cell and spatial transcriptomicsCancer Immunotherapy and BiomarkersImmune cells in cancer

High-definition spatial transcriptomic profiling of immune cell populations in colorectal cancer

Open access
Oliveira, Michelli Faria de, Romero, Juan Pablo, Chung, Meii, Williams, Stephen R., Gottscho, Andrew D., Gupta, Anushka, Pilipauskas, Susan E., Mohabbat, Seayar +10 more·2025·Nature Genetics

Abstract

A comprehensive understanding of cellular behavior and response to the tumor microenvironment (TME) in colorectal cancer (CRC) remains elusive. Here, we introduce the high-definition Visium spatial transcriptomic technology (Visium HD) and investigate formalin-fixed paraffin-embedded human CRC samples (n = 5). We demonstrate the high sensitivity, single-cell-scale resolution and spatial accuracy of Visium HD, generating a highly refined whole-transcriptome spatial profile of CRC samples. We identify transcriptomically distinct macrophage subpopulations in different spatial niches with potential pro-tumor and anti-tumor functions via interactions with tumor and T cells. In situ gene expression analysis validates our findings and localizes a clonally expanded T cell population close to macrophages with anti-tumor features. Our study demonstrates the power of high-resolution spatial technologies to understand cellular interactions in the TME and paves the way for larger studies that will unravel mechanisms and biomarkers of CRC biology, improving diagnosis and disease management strategies.

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Crossref · 10.1038/s41588-025-02193-3

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  • Vascular-immune interactions were primarily inferred from histological proximity, flow cytometry and gene-expression patterns.

    “Moreover, vascular-immune interactions were primarily inferred from histological proximity, flow cytometry and gene-expression patterns; spatial transcriptomics and single-cell multiomics approaches will be valuable for elucidating cell-type-specific crosstalk at single-cell resolution 54,55 .”

    From Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro (2026) · cites this paper as [54]

    The citation follows the sentence’s second clause. The Main section says spatial transcriptomics helps locate cell types and understand their interactions in colorectal tumors, supporting the proposed value of spatial approaches. It does not establish vascular–immune crosstalk specifically or the value of single-cell multiomics for studying it; the preceding claim about histology and flow cytometry is not supported by this paper. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 1

  1. Avraham-Davidi, I. et al. Spatially defined multicellular functional units in colorectal cancer revealed from single cell and spatial transcriptomics. eLife 14, RP104815 (2025).

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Authors
Oliveira, M. F. D., Romero, J. P., Chung, M., Williams, S. R., Gottscho, A. D., Gupta, A., Pilipauskas, S. E., Mohabbat, S., Raman, N., Sukovich, D. J., Patterson, D. M., Visium HD Development Team, de Oliveira, M. F., Romero, J. P., Williams, S. R., Patterson, D. M., Taylor, S. E. B., & Taylor, S. E. B.
Affiliations
10X Genomics (United States) (US)
Venue
Nature Genetics
Published
2025-06
Volume
57
Issue
6
Pages
1512-1523
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
OpenAlex
W4411069266
Cited by
321
References
56
Citations by year
2026: 253 · 2025: 68
FWCI
95.95
Type
journal article
Language
en
Open access
Locations
  • Nature Genetics (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
colorectal cancer, tumor microenvironment, spatial transcriptomics, Visium HD, macrophage subpopulations, T cell clonal expansion, immune cell interactions, formalin-fixed paraffin-embedded tissue, in situ gene expression, antitumor immunity
MeSH terms
Female, Humans, Macrophages, Male, T-Lymphocytes, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Gene Expression Profiling, Single-Cell Analysis, Tumor Microenvironment, Transcriptome

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