Gene expression
A single-cell atlas refines colorectal cancer subtypes
Open access · cc by · source: Europe PMC
Across ~487,829 cells from diverse CRC samples and cohorts, tumors show CMS-related programs plus immune/stromal continua; high CAF and C1Q+ TAM content track poorer outcomes and may simplify prognosis beyond bulk CMS alone.
Study at a glance
- Design
- Other — Single-cell atlas of CRC tumor/microenvironment relative to CMS, with external cohorts
- N
- N=16 · 16 primary patients (plus adjacent normals); ~487,829 cells across pooled cohorts
- Population
- Racially diverse CRC patients and external single-cell CRC cohorts
- Outcome
- Cellular CMS heterogeneity and CAF/C1Q+ TAM contributions to prognosis
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
Tumor cells recapitulate CMS subgroups but with significant intratumoral CMS heterogeneity. MSI-H (CMS1) and MSS tumors can look similar in epithelial pathway activation, yet MSI-H tumors show CD8+ cytotoxic T-cell infiltration patterns that help explain checkpoint-inhibitor responses. CRC transcriptomes form a tumor–immune–stromal continuum rather than only discrete bulk subtypes. Patients with high cancer-associated fibroblasts (CAFs) and C1Q+ TAM content have poorer outcomes; some CAF subtypes associate with immunotherapy resistance. Authors conclude CAF/C1Q+TAM signatures can explain much of CMS’s prognostic signal and may be therapeutically relevant.
Methodology
Authors argue bulk CMS mixes tumor and stroma, so they profiled racially diverse human CRC samples and multiple external cohorts (~487,829 single cells) to map cellular diversity in tumor and microenvironment compartments relative to consensus molecular subtypes (CMS).
Limitations
Does not prove that depleting CAFs or C1Q+ TAMs improves immunotherapy in a randomized trial. Continuum language means bulk CMS labels are still useful but incomplete — not that subtypes are meaningless. Cohort composition and correction notes in the literature should be checked before treating every numeric detail as final.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
scRNA-seq can separate definitive endoderm progenitors and point to hypoxia effects in hESC cultures.
In human ES differentiation, scRNA-seq separated definitive endoderm progenitors (PC5 signature) and motivated severe hypoxia experiments that increased CXCR4+ DE-like cells.
Scope note — different system — CRC tumor atlas, not stem-cell DE
Limits the claim's scope: a different population, assay, or outcome.
A CRC single-cell atlas links CMS labels to immune/stromal states and outcomes.
Across ~487,829 cells, tumor cells recapitulated CMS subgroups with intratumoral heterogeneity; MSI-H tumors showed CD8 cytotoxic infiltration patterns; high CAF and C1Q+ TAM content associated with poorer outcomes.
Evidence for the claim as stated.
hESC endoderm time courses, brain organoid atlases, and CRC tumor atlases all use scRNA-seq without answering the same biological question—do not average their findings into one ‘scRNA-seq result.’
Evidence for the claim as stated.
Method papers and toolboxes in the wider queue are not interchangeable with these empirical atlases; this page only cites studies that make a biological claim with single-cell profiles.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
hESC endoderm time courses, brain organoid atlases, and CRC tumor atlases all use scRNA-seq without answering the same biological question—do not average their findings into one ‘scRNA-seq result.’
Method papers and toolboxes in the wider queue are not interchangeable with these empirical atlases; this page only cites studies that make a biological claim with single-cell profiles.
Related papers in this topic
Same topic cluster — not a recommendation engine.