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We aimed to elucidate alterations in tuft cell populations during gastric atrophy and tumorigenesis in humans with correlative comparison to relevant mouse models. Tuft cell distribution was determined in human stomachs from organ donors and in gastric pathologies including M\u00e9n\u00e9trier's disease, <jats:italic>Helicobacter pylori<\/jats:italic> gastritis, intestinal metaplasia (IM), and gastric tumors. Tuft cell populations were examined in <jats:italic>Lrig1\u2010Kras<\/jats:italic><jats:sup><jats:italic>G12D<\/jats:italic><\/jats:sup>, <jats:italic>Mist1\u2010Kras<\/jats:italic><jats:sup><jats:italic>G12D<\/jats:italic><\/jats:sup>, and MT\u2010TGF\u03b1 mice. Tuft cells were evenly distributed throughout the entire normal human stomach, primarily concentrated in the isthmal region in the fundus. M\u00e9n\u00e9trier's disease stomach showed increased tuft cells. Similarly, Lrig1\u2010Kras mice and mice overexpressing TGF\u03b1 showed marked foveolar hyperplasia and expanded tuft cell populations. Human stomach with IM or dysplasia also showed increased tuft cell numbers. Similarly, Mist1\u2010Kras mice had increased numbers of tuft cells during metaplasia and dysplasia development. In human gastric cancers, tuft cells were rarely observed, but showed positive associations with well\u2010differentiated lesions. In mouse gastric cancer xenografts, tuft cells were restricted to dysplastic well\u2010differentiated mucinous cysts and were lost in less differentiated cancers. Taken together, tuft cell populations increased in atrophic human gastric pathologies, metaplasia, and dysplasia, but were decreased in gastric cancers. Similar findings were observed in mouse models, suggesting that, while tuft cells are associated with precancerous pathologies, their loss is most associated with the progression to invasive cancer.<\/jats:p>","DOI":"10.1002\/cjp2.352","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T09:34:12Z","timestamp":1703064852000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dynamic tuft cell expansion during gastric metaplasia and dysplasia"],"prefix":"10.1002","volume":"10","author":[{"given":"Bogun","family":"Jang","sequence":"first","affiliation":[{"name":"Section of Surgical Sciences Vanderbilt University Medical Center  Nashville TN USA"},{"name":"Jeju National University College of Medicine  Jeju Republic of Korea"},{"name":"Department of Pathology Jeju National University Hospital  Jeju Republic of 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