Spatial gene expression maps of the intestinal lymphoid follicle and associated epithelium identify zonated expression programs.

Noam Cohen,Milena Rozenberg,Shani Ben-Moshe,Adi Egozi,Hassan Massalha,Shalev Itzkovitz,Keren Bahar Halpern

doi:10.1371/journal.pbio.3001214

Abstract

The intestine is lined with isolated lymphoid follicles (ILFs) that facilitate sampling of luminal antigens to elicit immune responses. Technical challenges related to the scarcity and small sizes of ILFs and their follicle-associated epithelium (FAE) impeded the characterization of their spatial gene expression programs. Here, we combined RNA sequencing of laser capture microdissected tissues with single-molecule transcript imaging to obtain a spatial gene expression map of the ILF and its associated FAE in the mouse small intestine. We identified zonated expression programs in both follicles and FAEs, with a decrease in enterocyte antimicrobial and absorption programs and a partial induction of expression programs normally observed at the villus tip. We further identified Lepr+ subepithelial telocytes at the FAE top, which are distinct from villus tip Lgr5+ telocytes. Our analysis exposes the epithelial and mesenchymal cell states associated with ILFs.

Highlights

The intestine is lined with mucosa-associated lymphoid follicles that promote homeostatic response against luminal microbiota [1]
We found that some villus tip enterocyte genes, such as Cdh1, Cdkn1a, and the apolipoprotein genes Apoa1 and Apoa4 were elevated at the follicle-associated epithelium (FAE) top (FAET)
We found that FAE enterocytes exhibit a gene expression signature that is distinct from both enterocytes at the VB and at the villus tip

Summary

Introduction

The intestine is lined with mucosa-associated lymphoid follicles that promote homeostatic response against luminal microbiota [1]. These lymphoid follicles include 7 to 10 large Peyer’s patches (1 to 2 mm in diameter) [2], as well as smaller solitary intestinal lymphoid tissues (SILTs) that are up to 200 μm in diameter. The thin mucous layer enables apical–basolateral transport of antigens from the lumen across the FAE into the lamina propria by M cells, mediating the mucosal immune response [7].

Results

Discussion

Methods