Single-cell RNA sequencing (scRNA-seq) has revolutionised our understanding of the human gut by providing a high-resolution view of cellular diversity. In the healthy gut, scRNA-seq has unveiled remarkable variation among epithelial cells, immune cells, and other intestinal lineages, highlighting the complex interactions required for nutrient absorption and immune homeostasis.1,2 By analysing individual cells, scRNA-seq identifies rare and intermediate cell states that would be missed by traditional bulk sequencing.2 These insights are crucial for understanding gut physiology and identifying how cellular disruptions lead to disease.
In inflammatory bowel disease (IBD), scRNA-seq has been pivotal in mapping disease-specific cellular changes. For example, it has identified distinct pro-inflammatory immune cell populations and epithelial subtypes that contribute to chronic inflammation.3,4 In Crohn’s disease, scRNA-seq has revealed that epithelial cells re-activate developmental gene programmes seen in the fetal gut, which may drive the pathological remodelling of the intestinal barrier.4 Such findings underscore the importance of scRNA-seq in linking cellular processes to disease mechanisms.
Moreover, scRNA-seq has contributed to personalised medicine by identifying novel cellular markers and pathways that could serve as therapeutic targets. For instance, the identification of immune cell subsets in ulcerative colitis has opened new avenues for targeted drug discovery.3,5 Additionally, integrating scRNA-seq with genetic data helps pinpoint disease-critical cell types and pathways, offering insights into disease susceptibility and progression.5
Overall, single-cell RNA sequencing provides an unparalleled view of the cellular landscape in both health and disease, paving the way for more precise and effective therapeutic interventions in intestinal disorders.2,3,4
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