Understanding human gut diseases at single-cell resolution

Abstract

Our understanding of gut functioning and pathophysiology has grown considerably in the past decades, and advancing technologies enable us to deepen this understanding. Single-cell RNA sequencing (scRNA-seq) has opened a new realm of cellular diversity and transcriptional variation in the human gut at a high, single-cell resolution. ScRNA-seq has pushed the science of the digestive system forward by characterizing the function of distinct cell types within complex intestinal cellular environments, by illuminating the heterogeneity within specific cell populations and by identifying novel cell types in the human gut that could contribute to a variety of intestinal diseases. In this review, we highlight recent discoveries made with scRNA-seq that significantly advance our understanding of the human gut both in health and across the spectrum of gut diseases, including inflammatory bowel disease, colorectal carcinoma and celiac disease.

Figure 1

Gut disease-specific features identified by single-cell transcriptomics. The inner circle includes the cell types (in red color) that expand in disease and form key network hubs, mediating inter-lineage crosstalk. The outer circle highlights changes in the proportions of cell subtypes in each compartment that don’t directly contribute to the disease-associated cell–cell network but yet have detrimental effects for intestinal barrier homeostasis. Cell types in gray are depleted in active disease, while cell types in green considerably expand. Cell–cell interactions and their direction are marked by black arrows. Blue dashed arrows delineate the recruitment of circulating classical monocytes by activated endothelial cells, which in turn differentiate into pathogenic activated macrophages and DCs. Annotations: IAFs, inflammation-associated fibroblasts; CAFs, cancer-associated fibroblasts; DCs, dendritic cells; PCs, Paneth cells; PLCs, Paneth-like cells.