tetano
Editor, Senior Moderator
Genome Biol
. 2025 Mar 14;26(1):56.
doi: 10.1186/s13059-025-03499-5. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients
Yered Pita-Juarez[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Dimitra Karagkouni[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nikolaos Kalavros[SUP] #[/SUP][SUP] 1 3 4 [/SUP], Johannes C Melms[SUP] #[/SUP][SUP] 5 6 [/SUP], Sebastian Niezen[SUP] #[/SUP][SUP] 2 7 8 [/SUP], Toni M Delorey[SUP] #[/SUP][SUP] 9 [/SUP], Adam L Essene[SUP] 7 10 11 [/SUP], Olga R Brook[SUP] 12 [/SUP], Deepti Pant[SUP] 7 10 11 [/SUP], Disha Skelton-Badlani[SUP] 2 7 8 [/SUP], Pourya Naderi[SUP] 1 2 [/SUP], Pinzhu Huang[SUP] 2 7 8 [/SUP], Liuliu Pan[SUP] 13 [/SUP], Tyler Hether[SUP] 13 [/SUP], Tallulah S Andrews[SUP] 14 [/SUP], Carly G K Ziegler[SUP] 2 3 15 16 17 18 19 20 21 22 23 [/SUP], Jason Reeves[SUP] 13 [/SUP], Andriy Myloserdnyy[SUP] 2 7 8 [/SUP], Rachel Chen[SUP] 2 7 8 [/SUP], Andy Nam[SUP] 13 [/SUP], Stefan Phelan[SUP] 13 [/SUP], Yan Liang[SUP] 13 [/SUP], Mark Gregory[SUP] 13 [/SUP], Shanshan He[SUP] 13 [/SUP], Michael Patrick[SUP] 13 [/SUP], Tushar Rane[SUP] 13 [/SUP], Aster Wardhani[SUP] 13 [/SUP], Amit Dipak Amin[SUP] 5 6 [/SUP], Jana Biermann[SUP] 5 6 [/SUP], Hanina Hibshoosh[SUP] 24 [/SUP], Molly Veregge[SUP] 7 10 11 [/SUP], Zachary Kramer[SUP] 7 10 [/SUP], Christopher Jacobs[SUP] 7 10 11 [/SUP], Yusuf Yalcin[SUP] 2 7 8 [/SUP], Devan Phillips[SUP] 25 [/SUP], Michal Slyper[SUP] 25 [/SUP], Ayshwarya Subramanian[SUP] 9 [/SUP], Orr Ashenberg[SUP] 9 [/SUP], Zohar Bloom-Ackermann[SUP] 26 [/SUP], Victoria M Tran[SUP] 26 [/SUP], James Gomez[SUP] 26 [/SUP], Alexander Sturm[SUP] 26 [/SUP], Shuting Zhang[SUP] 26 [/SUP], Stephen J Fleming[SUP] 27 28 [/SUP], Sarah Warren[SUP] 13 [/SUP], Joseph Beechem[SUP] 13 [/SUP], Deborah Hung[SUP] #[/SUP][SUP] 26 29 30 [/SUP], Mehrtash Babadi[SUP] #[/SUP][SUP] 27 28 [/SUP], Robert F Padera Jr[SUP] #[/SUP][SUP] 31 [/SUP], Sonya A MacParland[SUP] #[/SUP][SUP] 15 32 33 [/SUP], Gary D Bader[SUP] #[/SUP][SUP] 34 35 [/SUP], Nasser Imad[SUP] #[/SUP][SUP] 1 [/SUP], Isaac H Solomon[SUP] #[/SUP][SUP] 31 [/SUP], Eric Miller[SUP] #[/SUP][SUP] 13 [/SUP], Stefan Riedel[SUP] #[/SUP][SUP] 1 2 [/SUP], Caroline B M Porter[SUP] #[/SUP][SUP] 9 [/SUP], Alexandra-Chloé Villani[SUP] #[/SUP][SUP] 3 36 37 38 [/SUP], Linus T-Y Tsai[SUP] #[/SUP][SUP] 2 3 7 10 11 [/SUP], Winston Hide[SUP] #[/SUP][SUP] 1 2 [/SUP], Gyongyi Szabo[SUP] #[/SUP][SUP] 2 3 7 8 [/SUP], Jonathan Hecht[SUP] #[/SUP][SUP] 1 2 [/SUP], Orit Rozenblatt-Rosen[SUP] #[/SUP][SUP] 9 25 [/SUP], Alex K Shalek[SUP] #[/SUP][SUP] 39 40 41 42 43 44 45 46 47 48 49 [/SUP], Benjamin Izar[SUP] #[/SUP][SUP] 50 51 52 53 54 [/SUP], Aviv Regev[SUP] #[/SUP][SUP] 55 56 [/SUP], Yury V Popov[SUP] #[/SUP][SUP] 57 58 59 [/SUP], Z Gordon Jiang[SUP] #[/SUP][SUP] 60 61 62 [/SUP], Ioannis S Vlachos[SUP] #[/SUP][SUP] 63 64 65 66 67 68 [/SUP]
Affiliations
Background: 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.
Results: 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 expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells.
Conclusions: Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
Keywords: COVID-19; Liver; SARS-CoV-2; Single-cell sequencing; Single-nucleus sequencing; Spatial transcriptomics.
. 2025 Mar 14;26(1):56.
doi: 10.1186/s13059-025-03499-5. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients
Yered Pita-Juarez[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Dimitra Karagkouni[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Nikolaos Kalavros[SUP] #[/SUP][SUP] 1 3 4 [/SUP], Johannes C Melms[SUP] #[/SUP][SUP] 5 6 [/SUP], Sebastian Niezen[SUP] #[/SUP][SUP] 2 7 8 [/SUP], Toni M Delorey[SUP] #[/SUP][SUP] 9 [/SUP], Adam L Essene[SUP] 7 10 11 [/SUP], Olga R Brook[SUP] 12 [/SUP], Deepti Pant[SUP] 7 10 11 [/SUP], Disha Skelton-Badlani[SUP] 2 7 8 [/SUP], Pourya Naderi[SUP] 1 2 [/SUP], Pinzhu Huang[SUP] 2 7 8 [/SUP], Liuliu Pan[SUP] 13 [/SUP], Tyler Hether[SUP] 13 [/SUP], Tallulah S Andrews[SUP] 14 [/SUP], Carly G K Ziegler[SUP] 2 3 15 16 17 18 19 20 21 22 23 [/SUP], Jason Reeves[SUP] 13 [/SUP], Andriy Myloserdnyy[SUP] 2 7 8 [/SUP], Rachel Chen[SUP] 2 7 8 [/SUP], Andy Nam[SUP] 13 [/SUP], Stefan Phelan[SUP] 13 [/SUP], Yan Liang[SUP] 13 [/SUP], Mark Gregory[SUP] 13 [/SUP], Shanshan He[SUP] 13 [/SUP], Michael Patrick[SUP] 13 [/SUP], Tushar Rane[SUP] 13 [/SUP], Aster Wardhani[SUP] 13 [/SUP], Amit Dipak Amin[SUP] 5 6 [/SUP], Jana Biermann[SUP] 5 6 [/SUP], Hanina Hibshoosh[SUP] 24 [/SUP], Molly Veregge[SUP] 7 10 11 [/SUP], Zachary Kramer[SUP] 7 10 [/SUP], Christopher Jacobs[SUP] 7 10 11 [/SUP], Yusuf Yalcin[SUP] 2 7 8 [/SUP], Devan Phillips[SUP] 25 [/SUP], Michal Slyper[SUP] 25 [/SUP], Ayshwarya Subramanian[SUP] 9 [/SUP], Orr Ashenberg[SUP] 9 [/SUP], Zohar Bloom-Ackermann[SUP] 26 [/SUP], Victoria M Tran[SUP] 26 [/SUP], James Gomez[SUP] 26 [/SUP], Alexander Sturm[SUP] 26 [/SUP], Shuting Zhang[SUP] 26 [/SUP], Stephen J Fleming[SUP] 27 28 [/SUP], Sarah Warren[SUP] 13 [/SUP], Joseph Beechem[SUP] 13 [/SUP], Deborah Hung[SUP] #[/SUP][SUP] 26 29 30 [/SUP], Mehrtash Babadi[SUP] #[/SUP][SUP] 27 28 [/SUP], Robert F Padera Jr[SUP] #[/SUP][SUP] 31 [/SUP], Sonya A MacParland[SUP] #[/SUP][SUP] 15 32 33 [/SUP], Gary D Bader[SUP] #[/SUP][SUP] 34 35 [/SUP], Nasser Imad[SUP] #[/SUP][SUP] 1 [/SUP], Isaac H Solomon[SUP] #[/SUP][SUP] 31 [/SUP], Eric Miller[SUP] #[/SUP][SUP] 13 [/SUP], Stefan Riedel[SUP] #[/SUP][SUP] 1 2 [/SUP], Caroline B M Porter[SUP] #[/SUP][SUP] 9 [/SUP], Alexandra-Chloé Villani[SUP] #[/SUP][SUP] 3 36 37 38 [/SUP], Linus T-Y Tsai[SUP] #[/SUP][SUP] 2 3 7 10 11 [/SUP], Winston Hide[SUP] #[/SUP][SUP] 1 2 [/SUP], Gyongyi Szabo[SUP] #[/SUP][SUP] 2 3 7 8 [/SUP], Jonathan Hecht[SUP] #[/SUP][SUP] 1 2 [/SUP], Orit Rozenblatt-Rosen[SUP] #[/SUP][SUP] 9 25 [/SUP], Alex K Shalek[SUP] #[/SUP][SUP] 39 40 41 42 43 44 45 46 47 48 49 [/SUP], Benjamin Izar[SUP] #[/SUP][SUP] 50 51 52 53 54 [/SUP], Aviv Regev[SUP] #[/SUP][SUP] 55 56 [/SUP], Yury V Popov[SUP] #[/SUP][SUP] 57 58 59 [/SUP], Z Gordon Jiang[SUP] #[/SUP][SUP] 60 61 62 [/SUP], Ioannis S Vlachos[SUP] #[/SUP][SUP] 63 64 65 66 67 68 [/SUP]
Affiliations
- PMID: 40087773
- PMCID: PMC11907808
- DOI: 10.1186/s13059-025-03499-5
Background: 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.
Results: 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 expansion, and fibrogenesis characteristic of COVID-19 cholangiopathy. We also observe Kupffer cell proliferation and erythrocyte progenitors for the first time in a human liver single-cell atlas. Despite the absence of a clinical acute liver injury phenotype, endothelial cell composition is dramatically impacted in COVID-19, concomitantly with extensive alterations and profibrogenic activation of reactive cholangiocytes and mesenchymal cells.
Conclusions: Our atlas provides novel insights into liver physiology and pathology in COVID-19 and forms a foundational resource for its investigation and understanding.
Keywords: COVID-19; Liver; SARS-CoV-2; Single-cell sequencing; Single-nucleus sequencing; Spatial transcriptomics.