{"doi":"10.1016/j.jcmgh.2021.10.005","title":"Moving Up a NOTCH: Defining the Stem Cell Niche in the Gastric Antrum","abstract":"Initially intestinal stem cells in the gastrointestinal tract were identified by their mitotic activity and ability to take up and retain radiolabeled nucleotides (eg, tritiated thymidine, bromodeoxyuridine).1Cairns J. Somatic stem cells and the kinetics of mutagenesis and carcinogenesis.Proc Natl Acad Sci U S A. 2002; 99: 10567-10570Crossref PubMed Scopus (204) Google Scholar,2Kim S.J. Cheung S. Hellerstein M.K. Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon.Am J Physiol Cell Physiol. 2004; 286: C1464-C1473Crossref PubMed Scopus (34) Google Scholar Wnt signaling was subsequently identified as the proliferative signal in the stem cell niche, with downstream targets (eg, Lgr5) expressed by actively cycling cells.3Vries R.G. Huch M. Clevers H. Stem cells and cancer of the stomach and intestine.Mol Oncol. 2010; 4: 373-384Crossref PubMed Scopus (91) Google Scholar,4Nalapareddy K. Geiger H. Analysis of aged dysfunctional intestinal stem cells.Methods Mol Biol. 2020; 2171: 41-52Crossref PubMed Scopus (1) Google Scholar Although the site of stem cells in the proximal stomach has been linked to the isthmus or “neck” where there is a transition at the upper one-third of the oxyntic gland between the luminal-facing foveolar cells and the midgland parietal cells, only the stem cells in the antral glands of the stomach adjacent to the proximal small intestine show a pattern of mitotic activity marked by Wnt-dependent Lgr5 expression analogous to the small intestine.5Mills J.C. Shivdasani R.A. Gastric epithelial stem cells.Gastroenterology. 2011; 140: 412-424Abstract Full Text Full Text PDF PubMed Scopus (129) Google Scholar The antral stem cell niche is also anatomically defined by an “isthmus,” approximately one-third from the crypt base. In the small intestine, the active stem cell niche is defined by 4–5 Lgr5+-WNT-regulated crypt base columnar cells at the base intercalated between Paneth cells, which generate antimicrobial peptides, such as lysozyme and defensins.6Yen T.H. Wright N.A. The gastrointestinal tract stem cell niche.Stem Cell Rev. 2006; 2: 203-212Crossref PubMed Scopus (215) Google Scholar,7Shaker A. Rubin D.C. Intestinal stem cells and epithelial-mesenchymal interactions in the crypt and stem cell niche.Transl Res. 2010; 156: 180-187Abstract Full Text Full Text PDF PubMed Scopus (77) Google Scholar However, despite the similarity in stem cell niches, the signaling pathways of the gastric antrum, also comprised of mitotically active and nondividing support cells, have been less well defined. In this issue, Samuelson and coworkers extend their prior studies by identifying Delta-like1 (DLL1) as the Notch receptor ligand expressed in the nonmitotic stem cell niche that communicates with the actively cycling Lgr5/Notch1/Sox9-positive cells.8Horita N. Keeley T.M. Hibdon E.S. Delgado E. Lafkas D. Siebel C.W. Samuelson L.C. Delta-like 1-expressing cells at the gland base promote proliferation of gastric antral stem cells in mouse.Cell Mol Gastroenterol Hepatol. 2022; 13: 275-287Abstract Full Text Full Text PDF Scopus (3) Google Scholar Because the Lgr5-positive stem cells at the crypt base express the Notch1 receptor, the authors concluded that nonproliferating mucous cells expressing DLL1 form the antral stem cell niche. Based on prior studies, these GSII lectin-positive niche cells are likely TFF2 and Muc6 positive and contribute to Notch-mediated antral tumors through activation of mTor.9Demitrack E.S. Gifford G.B. Keeley T.M. Carulli A.J. VanDussen K.L. Thomas D. Giordano T.J. Liu Z. Kopan R. Samuelson L.C. Notch signaling regulates gastric antral LGR5 stem cell function.EMBO J. 2015; 34: 2522-2536Crossref PubMed Scopus (57) Google Scholar Although Jagged 1 (Jag1) was the most abundant Notch ligand in the antral glands, its expression was restricted to the differentiated cell populations of the mid and upper antral gland marked by Muc5AC and FoxQ1.8Horita N. Keeley T.M. Hibd","journal":"Cellular and Molecular Gastroenterology and Hepatology","year":2021,"id":205421,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":279067,"name":"Juanita L. Merchant","orcid":"0000-0002-6559-8184","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:51:33.996102Z","pmid":"34728187","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}