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Combining scRNA\u2010seq and spatial transcriptomic analysis, the kinetic landscape of the liver microenvironment across time and space in AAV\u2010HBV mice, which develop from inflammation to ultimately hepatocellular carcinoma is generated. Kupffer cells (KCs), originally resided within the peri\u2010portal area, are persistently recruited to the HBV\u2010enriched peri\u2010central region via increased CXCL9 produced by endothelial cells, facilitating the interaction between KCs and HBV\n                    <jats:sup>+<\/jats:sup>\n                    hepatocytes to induce LXR\u03b1 deficiency\u2010mediated lipid metabolism disorders (LMD) in KCs. In turn, KCs with LMD elicited cancer stem cell formation from HBV\n                    <jats:sup>+<\/jats:sup>\n                    hepatocytes via Stat3 pathway, activated by the chemokine network within the crosstalk. Moreover, miR\u2010155\u2010mediated post\u2010transcriptional regulation and ASGR1\u2010dependent degradation collaboratively regulated LXR\u03b1 downregulation in KCs. LXR\u03b1 deficiency in KCs is also detected in the tumor tissues of HBV\n                    <jats:sup>+<\/jats:sup>\n                    patients compared to that of the normal and tumor\u2010adjacent tissue. Importantly, LXR\u03b1 upregulation in KCs constrained fibrosis and cancer stem cell formation. For the first time, the role of KC zonation in disease progression has been revealed, highlighting LXR\u03b1 in KCs as a promising target for the early intervention in the transition from CHB\u2010induced inflammation to cancer.\n                  <\/jats:p>","DOI":"10.1002\/advs.202510275","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T09:47:51Z","timestamp":1761817671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["CHB\u2010Induced Immune Zonation Chaos Elicited LXR\u03b1\u2010mediated Lipid Metabolism Disorders in Kupffer Cells to Induce Cancer Stem Cell Formation"],"prefix":"10.1002","volume":"13","author":[{"given":"Jingqi","family":"Shi","sequence":"first","affiliation":[{"name":"Bioinformatics Center of AMMS  Beijing 100850 P. R. 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