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Adv."],"published-print":{"date-parts":[[2026,2,20]]},"abstract":"<jats:p>The liver contains an intricate microstructure that is critical for proper liver function. Architectural disruption of this spatial structure is pathologic. Unfortunately, two-dimensional (2D) histopathology\u2014the gold standard for pathological understanding of many liver diseases\u2014can misrepresent or leave gaps in our understanding of complex 3D structural features. Here, we used immunostaining, tissue clearing, microscopy, and computational software to create 3D multilobular reconstructions of both nonfibrotic and cirrhotic human liver tissue. We found that spatial architecture in human cirrhotic liver samples with varying etiologies had sinusoid zonal dysregulation, reduction in glutamine synthetase\u2013expressing pericentral hepatocytes, regression of central vein networks, disruption of hepatic arterial networks, and fragmentation of biliary networks, which together suggest a pro-portalization\/decentralization phenotype in cirrhotic tissue. Further implementation of 3D pathological analyses may provide a deeper understanding of cirrhotic pathobiology and inspire treatments for liver disease.<\/jats:p>","DOI":"10.1126\/sciadv.adz2299","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T18:59:51Z","timestamp":1771441191000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["3D reconstruction of human liver tissue at cellular resolution"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1829-6511","authenticated-orcid":true,"given":"Wesley B.","family":"Fabyan","sequence":"first","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA."},{"name":"Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-0862","authenticated-orcid":true,"given":"Chelsea L.","family":"Fortin","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA."},{"name":"Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA."},{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2031-3148","authenticated-orcid":true,"given":"Dorice L.","family":"Goune","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA."},{"name":"Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi L.","family":"Kenerson","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3400-8479","authenticated-orcid":true,"given":"Susana P.","family":"Simmonds Bohorquez","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA."},{"name":"Institute for Stem Cells and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-3086","authenticated-orcid":true,"given":"Jonathan T. C.","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of Washington, Seattle, WA 98195, USA."},{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA."},{"name":"Department of Mechanical Engineering, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0235-6994","authenticated-orcid":true,"given":"Rotonya M.","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, WA 98195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond S. 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