crc-23-0142-s20.pdf (370.17 kB)
Figure S11 from Single-cell profiling uncovers a Muc4-expressing metaplastic gastric cell type sustained by Helicobacter pylori-driven inflammation
journal contributionposted on 2023-08-14, 13:20 authored by Valerie Phoebe O'Brien, Yuqi Kang, Meera K Shenoy, Greg Finak, William C Young, Julien Dubrulle, Lisa Koch, Armando E Rodriguez Martinez, Jeffery Williams, Elizabeth Donato, Surinder K. Batra, Cecilia C.S. Yeung, William M Grady, Meghan A Koch, Raphael Gottardo, Nina R. Salama
Gastric inflammation is greatest in Hp+KRAS+ mice.
ARTICLE ABSTRACTMechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA-seq showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and immunohistochemistry-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation.