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Numerous studies have shown that mesenchymal\u2010specific Lkb1 is sufficient for the development of PJS\u2010like polyps in mice. However, the cellular origin and components of these Lkb1\u2010associated polyps and underlying mechanisms remain elusive. In this study, we generated tamoxifen\u2010inducible\n                    <jats:italic>Lkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Myh11\u2010Cre\/ERT2<\/jats:italic>\n                    and\n                    <jats:italic>Lkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>PDGFR\u03b1\u2010Cre\/ERT2<\/jats:italic>\n                    mice, performed single\u2010cell RNA sequencing (scRNA\u2010seq) and imaging\u2010based lineage tracing, and aimed to investigate the cellular complexity of gastrointestinal polyps associated with PJS. We found that\n                    <jats:italic>Lkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/+<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Myh11\u2010Cre\/ERT2<\/jats:italic>\n                    mice developed gastrointestinal polyps starting at 9\u2009months after tamoxifen treatment. scRNA\u2010seq revealed aberrant stem cell\u2010like characteristics of epithelial cells from polyp tissues of\n                    <jats:italic>Lkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/+<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>Myh11\u2010Cre\/ERT2<\/jats:italic>\n                    mice. The Lkb1\u2010associated polyps were further characterized by a branching smooth muscle core, abundant extracellular matrix deposition, and high immune cell infiltration. In addition, the Spp1\u2013Cd44 or Spp1\u2013Itga8\/Itgb1 axes were identified as important interactions among epithelial, mesenchymal, and immune compartments in Lkb1\u2010associated polyps. These characteristics of gastrointestinal polyps were also demonstrated in another mouse model, tamoxifen\u2010inducible\n                    <jats:italic>Lkb1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>flox\/flox<\/jats:italic>\n                    <\/jats:sup>\n                    ;\n                    <jats:italic>PDGFR\u03b1\u2010Cre\/ERT2<\/jats:italic>\n                    mice, which developed obvious gastrointestinal polyps as early as 2\u20133\u2009months after tamoxifen treatment. Our findings further confirm the critical role of mesenchymal\n                    <jats:italic>Lkb1\/Stk11<\/jats:italic>\n                    in gastrointestinal polyposis and provide novel insight into the cellular complexity of Lkb1\u2010associated polyp biology. \u00a9 2024 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.6259","type":"journal-article","created":{"date-parts":[[2024,2,23]],"date-time":"2024-02-23T03:28:19Z","timestamp":1708658899000},"page":"47-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cellular and molecular characteristics of stromal Lkb1 deficiency\u2010induced gastrointestinal polyposis based on single\u2010cell\n                    <scp>RNA<\/scp>\n                    sequencing"],"prefix":"10.1002","volume":"263","author":[{"given":"Zhaohua","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangjing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunwen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqi","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Huo","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghong","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6717-9039","authenticated-orcid":false,"given":"Ben","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai PR 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