biostudies-literaturePita-Juarez YOffice of Research Infrastructure Programs, National Institutes of HealthNIDDK NIH HHSNational Blood Clot AllianceU.S. Food and Drug AdministrationNCI NIH HHSNIH Support GrantGates Foundation56https://www.ebi.ac.uk/biostudies/studies/S-EPMC11907808biostudies-literatureUnknown26(1)<h4>Background</h4>The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents.<h4>Results</h4>We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansioGenome biologyA single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.PMC11907808S10RR027050PR200524P1P30CA013696R01 CA258776R01 HL129506-07R37CA258829HHSF223201810172CINV-027498P30 DK046200U54CA225088R21CA263381P30 DK135043Massachusetts Life Sciences CenterK08CA222663Phelan SMyloserdnyy ALiang YAshenberg OWarren SPatrick MZhang SRane TSubramanian ASturm ATsai LTEssene ALHuang PIzar BVillani ACJiang ZGHibshoosh HSlyper MChen RHecht JRozenblatt-Rosen OPita-Juarez YNiezen SWardhani AKramer ZMelms JCBeechem JTran VMHe SDelorey TMSzabo GKaragkouni DBiermann JJacobs CBrook ORPadera RFMacParland SAPopov YVRiedel SYalcin YHide WHung DFleming SJVlachos ISBader GDBloom-Ackermann ZBabadi MPhillips DMiller EPorter CBMAmin ADZiegler CGKReeves JNam AImad NSolomon IHGomez JPant DRegev AShalek AKHether TNaderi PSkelton-Badlani DPan LKalavros NAndrews TSGregory MVeregge MfalseA single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.<h4>Background</h4>The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these in the context of liver function, we perform single-nucleus RNA-seq and spatial transcriptomic profiling of livers from 17 COVID-19 decedents.<h4>Results</h4>We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, and a central role in a pro-fibrotic TGFβ signaling cell-cell communications network. Integrated analysis and comparisons with healthy controls reveal extensive changes in the cellular composition and expression states in COVID-19 liver, providing the underpinning of hepatocellular injury, ductular reaction, pathologic vascular expansio2025-01-01T00:00:00Z2025 Mar2026-06-01T22:54:27.831Z2025-04-06T10:47:51.989ZS-EPMC119078084008777310.1186/s13059-025-03499-5