{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:58:15Z","timestamp":1791608295639,"version":"4.3.4"},"reference-count":83,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA0917000"],"award-info":[{"award-number":["2024YFA0917000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["32425012"],"award-info":[{"award-number":["32425012"]}],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Insect Science"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Honeybees are key pollinators of flowering plants, and their health is closely associated with gut function. The function is regionally specialized, with nutrient absorption distributed across distinct gut compartments and influenced by the gut microbiota. Here, we constructed a single\u2010nucleus transcriptomic atlas of the honeybee gut under microbiota\u2010free and conventional (CV) conditions and uncovered a microbiota\u2010dependent mechanism regulating intestinal homeostasis. We characterized major intestinal cell types in the honeybee, including intestinal stem cell\/enteroblast (ISC\/EB), enterocyte (EC), enteroendocrine cell (EE), visceral muscle, and enteric neurons. The cellular data uncovered that regional functional specialization of the intestine is associated with the spatial distribution of EC and EE cell subtypes. Intriguingly, we found that microbiota significantly alter cell composition and gene expression in the ileum, particularly within the ISC\/EB population. <jats:italic>Relish<\/jats:italic>, a conserved nuclear factor\u2010<jats:italic>\u03ba<\/jats:italic>B transcription factor in the immune deficiency pathway, was upregulated in the ISC\/EB within the ileum of CV bees. The gene regulatory network (GRN) revealed that the Relish regulon is explicitly activated in ISC\/EB of CV bees, promoting ISC\/EB toward ECs by directly regulating differentiation factors.Our study highlights the cellular and regional complexity of the honeybee gut and demonstrates that region\u2010specific microbiota may modulate GRN in ISC\/EBs, thereby shaping epithelial cell composition and maintaining intestinal homeostasis. This work provides a valuable resource for understanding host\u2013microbiota interactions in honeybees and serves as a reference to study gut function, immune regulation, and bee health at single\u2010cell resolution.<\/jats:p>","DOI":"10.1111\/1744-7917.70157","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T06:43:19Z","timestamp":1757659399000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiota shape gene regulatory networks to direct intestinal stem cell differentiation trajectories in <i>Apis mellifera<\/i>"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0697-4899","authenticated-orcid":false,"given":"Huiling","family":"Liu","sequence":"first","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Meng","sequence":"additional","affiliation":[{"name":"BGI\u2010Qingdao  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"BGI\u2010Qingdao  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingkun","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Food Science and Engineering Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9235-652X","authenticated-orcid":false,"given":"Xiaohuan","family":"Mu","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zheng","sequence":"additional","affiliation":[{"name":"Shandong Institute of Plant Protection Shandong Academy of Agricultural Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Shandong Institute of Plant Protection Shandong Academy of Agricultural Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shandong Institute of Plant Protection Shandong Academy of Agricultural Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3074-3860","authenticated-orcid":false,"given":"Xiaofei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Shandong Institute of Plant Protection Shandong Academy of Agricultural Sciences  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Liu","sequence":"additional","affiliation":[{"name":"BGI\u2010Qingdao  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-1675","authenticated-orcid":false,"given":"Hao","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Food Science and Nutritional Engineering China Agricultural University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single\u2010cell regulatory network inference and clustering","volume":"14","author":"Aibar S.","year":"2017","journal-title":"Nature Methods"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2020.100954","article-title":"IRBIT directs differentiation of intestinal stem cell progeny to maintain tissue homeostasis","volume":"23","author":"Arnaoutov A.","year":"2020","journal-title":"iScience"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/1744-7917.12868","article-title":"Regulatory mechanisms of microbial homeostasis in insect gut","volume":"28","author":"Bai S.","year":"2021","journal-title":"Insect 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