Single cell RNA-sequencing profiling to improve the translation between human IBD and in vivo models

Abstract

Inflammatory bowel disease (IBD) is an umbrella term for two conditions (Crohn's Disease and Ulcerative Colitis) that is characterized by chronic inflammation of the gastrointestinal tract. The use of pre-clinical animal models has been invaluable for the understanding of potential disease mechanisms. However, despite promising results of numerous therapeutics in mouse colitis models, many of these therapies did not show clinical benefits in patients with IBD. Single cell RNA-sequencing (scRNA-seq) has recently revolutionized our understanding of complex interactions between the immune system, stromal cells, and epithelial cells by mapping novel cell subpopulations and their remodeling during disease. This technology has not been widely applied to pre-clinical models of IBD. ScRNA-seq profiling of murine models may provide an opportunity to increase the translatability into the clinic, and to choose the most appropriate model to test hypotheses and novel therapeutics. In this review, we have summarized some of the key findings at the single cell transcriptomic level in IBD, how specific signatures have been functionally validated in vivo, and highlighted the similarities and differences between scRNA-seq findings in human IBD and experimental mouse models. In each section of this review, we highlight the importance of utilizing this technology to find the most suitable or translational models of IBD based on the cellular therapeutic target.

Keywords: Inflammatory bowel disease (IBD); epithelial cell; immune cell; pre-clinical models; single cell RNA-sequencing (scRNA-seq); stromal cell.

Figure 1

Summary of epithelial cell, stromal cell, and immune cell populations identified by scRNA-seq in the DSS-induced colitis model and human IBD. Highlighted key cell populations identified in this review that describe similar and different cell populations between the DSS-colitis pre-clinical model and human IBD.

Figure 2

Summary figure of how translating single cell findings in human to pre-clinical models improves our understanding of disease. Human IBD gene signatures at the single cell level could be overlayed with single cell gene signatures from multiple pre-clinical models of IBD allowing for data-driven selection of the most appropriate pre-clinical model to test novel biology, questions, and therapeutics.