Single-cell and spatial technologies reveal UC pathogenesis insights but face sample size and phenotype heterogeneity limits.
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Key Takeaway
Note that scRNA-seq and spatial studies offer pathogenesis insights but are limited by small samples and phenotype heterogeneity.
A systematic review assessed the utility of single cell RNA sequencing (scRNA-seq), spatial transcriptomic (ST), and proteomic (SP) technologies in adult ulcerative colitis cohorts. These advanced technologies were examined for their ability to provide insights into disease pathogenesis and treatment response within colonic tissue.
Results from the review indicate that these methods reveal alterations across the innate and adaptive immune systems, as well as stromal and epithelial compartments. Spatial studies specifically provided insights into the cellular composition of the UC microenvironment and identified inflammatory features distinguishing treatment responders from non-responders. Additionally, these technologies offered insights into ligand-receptor interactions, which may serve as potential spatial biomarkers and therapeutic targets.
Safety and tolerability data were not reported in the included studies. The review highlights significant limitations, including small sample sizes and heterogeneous UC phenotypes across the analyzed cohorts. These factors constrain the generalizability of the findings and the robustness of the observed associations.
Given the methodological constraints, the clinical relevance of these technologies for routine practice remains uncertain. Clinicians should interpret these findings as preliminary evidence that deepens biological understanding rather than established clinical guidelines for ulcerative colitis management.
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View Original Abstract ↓
IntroductionUlcerative colitis (UC) is driven by mucosal inflammation and epithelial injury. Single cell RNA sequencing (scRNA-seq) enables high resolution profiling of immune, stromal and epithelial compartments in UC, whilst spatial transcriptomic (ST) and proteomic (SP) enable interrogation of cell-cell interactions, niche-specific expression profiles, and spatially restricted pathological processes. Although scRNA-seq, ST, and SP technologies have been rapidly evolved in the past ten years, relatively limited clinical applications have been demonstrated. This systematic review aims at comprehensively analysing current evidence in UC studies as an approach to identifying key limitations and proposing recommendations for strengthening future spatial research towards translations into clinics.MethodsA comprehensive search of Embase, Medline, and grey literature was conducted to identify studies using scRNA-seq or spatial transcriptomic or proteomic technologies in adult UC cohorts. Outcomes of interest included insights into disease pathogenesis or treatment response.ResultsscRNA-seq studies revealed alterations across the innate and adaptive immune systems, as well as stromal and epithelial compartments in UC colonic tissue. Spatial studies provided insights into: (i) cellular composition of the UC microenvironment; (ii) inflammatory features in treatment responders versus non-responders; and (iii) ligand-receptor interactions as potential spatial biomarkers and therapeutic targets.ConclusionOverall, single-cell and spatial studies are deepening our understanding of UC pathogenesis and treatment response. However, they are often limited by small sample sizes and heterogeneous UC phenotypes. Future studies should prioritise robust cohort design and careful sample stratification. This will be critical to generating mechanistically precise, reproducible, and clinically meaningful insights into the heterogeneity of UC pathogenesis and treatment response.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024601628.
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