Cellular origins and lineage relationships of the intestinal epithelium

Knowledge of the development and hierarchical organization of tissues is key to understanding how they are perturbed in injury and disease, as well as how they may be therapeutically manipulated to restore homeostasis. The rapidly regenerating intestinal epithelium harbors diverse cell types and their lineage relationships have been studied using numerous approaches, from classical label-retaining and genetic lineage tracing methods to novel transcriptome-based annotations. Here, we describe the developmental trajectories that dictate differentiation and lineage specification in the intestinal epithelium. We focus on the most recent single-cell RNA-sequencing (scRNA-seq)-based strategies for understanding intestinal epithelial cell lineage relationships, underscoring how they have refined our view of the development of this tissue and highlighting their advantages and limitations. We emphasize how these technologies have been applied to understand the dynamics of intestinal epithelial cells in homeostatic and injury-induced regeneration models.