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Its highly organized vascular system plays a crucial role in maintaining functional zonation and tissue homeostasis. Within the liver, the hepatic artery, portal vein, hepatic vein, bile duct, and nerve networks intertwine to form an intricate three-dimensional architecture; however, traditional two-dimensional imaging fails to reveal their true spatial relationships, and current three-dimensional imaging methods remain insufficient to capture fine structural details. To achieve comprehensive visualization of these multi-ductal systems, we established a high-resolution three-dimensional imaging platform that combines multicolor perfusion of metallic compound nanoparticles (MCNPs) with an optimized tissue-clearing protocol (Liver-CUBIC), enabling simultaneous 3D reconstruction of the portal vein, hepatic artery, bile duct, and hepatic vein in mouse livers. Based on these data, we identified and defined a previously unrecognized structure located in the outer layer of the portal vein, termed the Periportal Lamellar Complex (PLC). The PLC encircles the portal vein between the vascular endothelium and the perisinusoidal region, exhibits low-permeability barrier characteristics, and contains a distinctive population of CD34\u207aSca-1\u207a endothelial cells. During liver fibrosis, the PLC extends from the portal vein toward the hepatic lobule, forming a structural scaffold that guides bile duct and nerve migration.<\/jats:p>","DOI":"10.1101\/2025.08.29.673025","type":"posted-content","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T16:40:15Z","timestamp":1756917615000},"source":"Crossref","is-referenced-by-count":0,"title":["A Novel 3D Visualization Method in Mice Identifies the Periportal Lamellar Complex (PLC) as a Key Regulator of Hepatic Ductal and Neuronal Branching Morphogenesis"],"prefix":"10.64898","author":[{"given":"Tongtong","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujun","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihan","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Chen","sequence":"additional","affiliation":[{"name":"Chengdu Minghong Tiancheng Technology Co., Ltd, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhong","sequence":"additional","affiliation":[{"name":"Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoxin","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banglei","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-0495","authenticated-orcid":false,"given":"Chong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjian","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041806151080000_2025.08.29.673025v6.1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg5733"},{"key":"2026041806151080000_2025.08.29.673025v6.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2024.104585"},{"key":"2026041806151080000_2025.08.29.673025v6.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V122.21.583.583"},{"key":"2026041806151080000_2025.08.29.673025v6.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2016.08.001"},{"key":"2026041806151080000_2025.08.29.673025v6.5","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i47.8831"},{"key":"2026041806151080000_2025.08.29.673025v6.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0125-y"},{"key":"2026041806151080000_2025.08.29.673025v6.7","doi-asserted-by":"crossref","unstructured":"Beckh, K. , Fuchs, E. , Ball\u00e9, C. , & Jungermann, K . 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