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It is characterized by extensive metabolic reprogramming, resulting in acute metabolic loss of function and maladaptive repair that can prime the organ for fibrosis rather than functional regeneration. To understand how intercellular communication dictates these outcomes, we performed cell type-specific bulk RNA-sequencing on hepatocytes (HEP), hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs), Kupffer cells (KC), and CD45+ leukocytes (CD45) from mice following polymicrobial sepsis. Cell-cell communication analyses using CellChat and NicheNet revealed a clear reorganization of the hepatic environment. While HSCs remain largely quiescent during homeostasis, after sepsis, they become the liver\u2019s central signaling hub and broadcast potent fibrogenic and chemotactic signals (e.g., Ccl7) to surrounding cells. This actively suppresses hepatocyte metabolic functions, promotes leukocyte infiltration, and may further initiate early fibrogenic priming. Our findings highlight HSCs as regulators during septic acute liver injury, revealing communication nodes that could be targeted to constrain fibrosis responses and promote normal functions and repair.<\/jats:p>","DOI":"10.3390\/cells15110968","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T10:19:52Z","timestamp":1779877192000},"page":"968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polymicrobial Sepsis-Induced Changes in Hepatic Stellate Cell Communication in Male C57BL\/6J Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Steven","family":"Timmermans","sequence":"first","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Van Dender","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5246-1923","authenticated-orcid":false,"given":"Maxime","family":"Roes","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9530-4898","authenticated-orcid":false,"given":"Elise","family":"Moens","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4227-2894","authenticated-orcid":false,"given":"Tineke","family":"Vanderhaeghen","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-6476","authenticated-orcid":false,"given":"Jolien","family":"Vandewalle","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-036X","authenticated-orcid":false,"given":"Claude","family":"Libert","sequence":"additional","affiliation":[{"name":"Center for Inflammation Research, Vlaams Instituut voor Biotechnologie (VIB), 9052 Ghent, Belgium"},{"name":"Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"ref_1","first-page":"8","article-title":"Liver Architecture","volume":"46","author":"Sasse","year":"1992","journal-title":"Enzyme"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"R1147","DOI":"10.1016\/j.cub.2017.09.019","article-title":"The Liver","volume":"27","author":"Trefts","year":"2017","journal-title":"Curr. 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