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Biosci. (Landmark Ed)"],"abstract":"<jats:p>Objective: To generate a single-cell atlas of colorectal cancer (CRC) development in Lynch syndrome (LS), and to delineate the associated cellular reprogramming and intercellular communication networks. Methods: We performed single-cell RNA sequencing (scRNA-seq) on matched normal mucosa, adenoma, and carcinoma tissues obtained from patients with LS. Following quality control and batch-effect correction, we used the Uniform Manifold Approximation and Projection (UMAP) clustering and marker gene analyses to annotate cell types, differential expression analyses to identify stage-specific genes, and GSVA analyses to assess pathway activity. Functional assays with patient-derived organoids and transwell experiments were employed to validate the role of DMBT1. Cell\u2013cell communication networks were inferred using Cell Chat. Results: We identified twelve distinct cell clusters and observed marked shifts in cellular composition during CRC progression, including increased T lymphocytes and macrophages and decreased epithelial cells. Trajectory analyses suggested a potential differentiation path from BEST4+ to CEMIP+\/EGFR+ epithelial cells. DMBT1 was consistently down-regulated and its depletion activated the WNT\/\u03b2-catenin pathway, enhancing organoid growth and cell migration. Expansion of CCR8+ regulatory T cells and C1QC+\/IDO1+\/IL1B+ macrophages indicated an immunosuppressive and pro-tumorigenic microenvironment. Conclusions: This study provides a comprehensive single-cell resource for LS-associated CRC and highlights DMBT1 loss, epithelial remodelling, and immune dysregulation as potential therapeutic targets.<\/jats:p>","DOI":"10.31083\/fbl47730","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:29:27Z","timestamp":1777454967000},"source":"Crossref","is-referenced-by-count":0,"title":["From Normal Mucosa to Colorectal Cancer in Lynch Syndrome: Single-Cell Dissection of Cellular Heterogeneity and Communication Networks"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1161-0480","authenticated-orcid":true,"given":"Shangxiang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jishen","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengkai","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinzhong","family":"Duanmu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7142-0139","authenticated-orcid":true,"given":"Qunguang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, 330006 Nanchang, Jiangxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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