Figure 4. Intestinal Niches.

(A) Before the advent of scRNA-Seq, knowledge of the intestinal niche was limited. In the intestine, Lgr5⁺ISCs lie adjacent to Paneth cells that secrete Wnt and EGF ligands that are crucial for ISC maintenance. In addition, Wnt ligands are secreted by the mesenchymal compartment, but the cellular composition of this compartment was unknown.

(B) Single-cell analysis of the intestinal epithelium has shed light on many components of the niche. In the small intestine, a subset of Lgr5⁺ ISCs express MHC-II and interact with Tregs that control the ISC pool.

(C) During helminth infection, epithelial cell populations change, giving rise to an increase in goblet and tuft cells. MHCII-expressing ISC subsets increase innumber and mediate these changes via interaction with T_H2 cells.

(D) Prior to scRNA-seq studies, the mesenchymal niche in the colon was thought to be the major source of Wnt ligands, but its composition was largely unknown.(E) In the mesenchymal compartment, eight subpopulations of mesenchymal cells (denoted by different colors) were identified by scRNA-Seq, which also highlighted the overlap between Foxl1⁺ and Gli1⁺ cells that secrete Wnt ligands.

(F) Inflammatory bowel disease (IBD) remodels the intestinal epithelium. scRNA-Seq identified expansion of inflammatory mesenchymal cells in IBD patients and loss of Wnt-secreting mesenchymal cells, as well as expansion of microfold cells.