“We see this atlas providing a foundation for investigating many different questions about the pathology in the gut, effects of drug-induced gut toxicities and for identifying and examining important cells, interactions, and biomarkers,” coauthor Ramnik Xavier, a member of the Broad Institute of MIT and Harvard University, says in a press release.
Xavier and colleagues collected tissue from the small intestine epithelium of mice and built transcriptional profiles using RNAseq. One of the striking revelations was the discovery of new subtypes of tuft cells, the sensory cells that bear taste receptors to detect pathogens. “We were surprised to see that expression of the gene TSLP—which encodes a cytokine long known to be involved in epithelial-induced inflammation—was exclusive to a particular subset of tuft cells,” coauthor Adam Haber, a postdoc at the Broad and MIT, says in the release. “This suggests a significant ‘lookout’ role for these recently characterized cells.”
The researchers also infected mice with either Salmonella or a roundworm, Heligmosomoides polygyrus, then analyzed a few thousands cells individually to look for infection-related changes. They observed a boost in the expression of genes related to inflammation and immune defense, as well as a change in the overall cellular makeup of the intestine. After bacterial infection, for instance, mice had more mature enterocytes and fewer stem cells than controls. In response to the worm, mice had more so-called goblet cells—which, the authors note, respond to the parasite—and fewer enterocytes.
“Although many studies have demonstrated that goblet cells and, more recently, that tuft cells accumulate and respond to parasites, our analysis reveals that this restructuring of the epithelial barrier is specific to the identity of the pathogen,” the authors write in their report.