Single cell RNA sequencing of the human gut in health and disease

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

References

  1. Bigaeva E, Uniken Venema WT, Weersma RK, Festen EA. Understanding human gut diseases at single-cell resolution. Human Molecular Genetics. 2020 Sep 15;29(R1):R51-8.
  2. Yan H, Ye Y, Zhao H, Zuo H, Li Y. Single-Cell RNA sequencing for analyzing the intestinal tract in healthy and diseased individuals. Frontiers in Cell and Developmental Biology. 2022 Jul 7;10:915654.
  3. Corridoni D, Chapman T, Antanaviciute A, Satsangi J, Simmons A. Inflammatory bowel disease through the lens of single-cell RNA-seq technologies. Inflammatory bowel diseases. 2020 Nov;26(11):1658-68.
  4. Elmentaite R, Ross AD, Roberts K, James KR, Ortmann D, Gomes T, Nayak K, Tuck L, Pritchard S, Bayraktar OA, Heuschkel R. Single-cell sequencing of developing human gut reveals transcriptional links to childhood Crohn’s disease. Developmental cell. 2020 Dec 21;55(6):771-83.
  5. Jagadeesh KA, Dey KK, Montoro DT, Mohan R, Gazal S, Engreitz JM, Xavier RJ, Price AL, Regev A. Identifying disease-critical cell types and cellular processes across the human body by integration of single-cell profiles and human genetics. bioRxiv. 2021 Mar 19:2021-03.