Single-Cell Sequencing Approach Homes in on Signaling Pathway in Gastric Cell Differentiation 

Researchers have uncovered the signaling pathways involved in the renewal of cells in the glandular stomach. In their study appearing in Nature Communications, researchers from the Nara Institute of Science and Technology in Japan used the single-cell RNA sequencing method Quartz-Seq2 to examine gene expression in progenitor cells as they differentiate into pit cells, neck cells, and parietal cells within mice. Defects in the differentiation of gastric progenitor cells have been linked to a number of diseases, including gastritis and gastric cancer. With a combination of pseudotime gene analysis and analyses in gastric organoids, the researchers found that EGFR-ERK signaling appears to promote differentiation, while NF-κB signaling promotes keeping the cells in an undifferentiated state. Further, inhibiting EGFR pharmacologically led to a decrease in the number of pit cells. "We knew that EGFR signaling is intricately involved in gastric cancers and several EGF receptors are overexpressed in various cancers," senior author Akira Kurisaki from NAIST says in a statement. "However, it was a pleasant surprise to find through our single-cell analysis that EGFR signaling has a differentiation-promoting role rather than a mitogenic role in healthy gastric homeostasis."