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| 001 | 299785 | ||
| 005 | 20250416163106.0 | ||
| 024 | 7 | _ | |a 10.1038/s41586-025-08677-w |2 doi |
| 024 | 7 | _ | |a pmid:40074890 |2 pmid |
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| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Sugimoto, Atsushi |0 0000-0003-3311-2562 |b 0 |
| 245 | _ | _ | |a Hepatic stellate cells control liver zonation, size and functions via R-spondin 3. |
| 260 | _ | _ | |a London [u.a.] |c 2025 |b Nature Publ. Group |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1744813824_25114 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:A190# / 640, pages 752–761 (2025) |
| 520 | _ | _ | |a Hepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood1-5. Here we demonstrate that genetic depletion of HSCs changes WNT activity and zonation of hepatocytes, leading to marked alterations in liver regeneration, cytochrome P450 metabolism and injury. We identify R-spondin 3 (RSPO3), an HSC-enriched modulator of WNT signalling, as responsible for these hepatocyte-regulatory effects of HSCs. HSC-selective deletion of Rspo3 phenocopies the effects of HSC depletion on hepatocyte gene expression, zonation, liver size, regeneration and cytochrome P450-mediated detoxification, and exacerbates alcohol-associated and metabolic dysfunction-associated steatotic liver disease. RSPO3 expression decreases with HSC activation and is inversely associated with outcomes in patients with alcohol-associated and metabolic dysfunction-associated steatotic liver disease. These protective and hepatocyte-regulating functions of HSCs via RSPO3 resemble the R-spondin-expressing stromal niche in other organs and should be integrated into current therapeutic concepts. |
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| 700 | 1 | _ | |a Saito, Yoshinobu |0 0000-0002-0624-0449 |b 1 |
| 700 | 1 | _ | |a Wang, Guanxiong |0 P:(DE-He78)8e8c59b5f06ec6da46af280f37a413c0 |b 2 |e First author |u dkfz |
| 700 | 1 | _ | |a Sun, Qiuyan |b 3 |
| 700 | 1 | _ | |a Yin, Chuan |b 4 |
| 700 | 1 | _ | |a Lee, Ki Hong |0 P:(DE-He78)5db788041043691b6a2f18e8ba5c73ae |b 5 |u dkfz |
| 700 | 1 | _ | |a Geng, Yana |b 6 |
| 700 | 1 | _ | |a Rajbhandari, Presha |0 0000-0003-2184-7238 |b 7 |
| 700 | 1 | _ | |a Hernandez, Celine |b 8 |
| 700 | 1 | _ | |a Steffani, Marcella |0 0000-0002-7439-7851 |b 9 |
| 700 | 1 | _ | |a Qie, Jingran |b 10 |
| 700 | 1 | _ | |a Savage, Thomas |0 0000-0002-6618-2973 |b 11 |
| 700 | 1 | _ | |a Goyal, Dhruv M |0 0009-0007-6454-2158 |b 12 |
| 700 | 1 | _ | |a Ray, Kevin C |b 13 |
| 700 | 1 | _ | |a Neelakantan, Taruna V |b 14 |
| 700 | 1 | _ | |a Yin, Deqi |b 15 |
| 700 | 1 | _ | |a Melms, Johannes |0 0000-0002-5410-6586 |b 16 |
| 700 | 1 | _ | |a Lehrich, Brandon M |b 17 |
| 700 | 1 | _ | |a Yasaka, Tyler M |0 0000-0002-8482-0369 |b 18 |
| 700 | 1 | _ | |a Liu, Silvia |b 19 |
| 700 | 1 | _ | |a Oertel, Michael |b 20 |
| 700 | 1 | _ | |a Lan, Tian |b 21 |
| 700 | 1 | _ | |a Guillot, Adrien |0 0000-0002-6002-9986 |b 22 |
| 700 | 1 | _ | |a Peiseler, Moritz |b 23 |
| 700 | 1 | _ | |a Filliol, Aveline |0 0000-0002-1345-8147 |b 24 |
| 700 | 1 | _ | |a Kanzaki, Hiroaki |b 25 |
| 700 | 1 | _ | |a Fujiwara, Naoto |b 26 |
| 700 | 1 | _ | |a Ravi, Samhita |0 0000-0002-6731-734X |b 27 |
| 700 | 1 | _ | |a Izar, Benjamin |0 0000-0003-2379-6702 |b 28 |
| 700 | 1 | _ | |a Brosch, Mario |b 29 |
| 700 | 1 | _ | |a Hampe, Jochen |b 30 |
| 700 | 1 | _ | |a Remotti, Helen |b 31 |
| 700 | 1 | _ | |a Argemi, Josepmaria |0 0000-0003-1696-7753 |b 32 |
| 700 | 1 | _ | |a Sun, Zhaoli |b 33 |
| 700 | 1 | _ | |a Kendall, Timothy J |0 0000-0002-4174-2786 |b 34 |
| 700 | 1 | _ | |a Hoshida, Yujin |0 0000-0001-9430-1426 |b 35 |
| 700 | 1 | _ | |a Tacke, Frank |0 0000-0001-6206-0226 |b 36 |
| 700 | 1 | _ | |a Fallowfield, Jonathan A |0 0000-0002-5741-1471 |b 37 |
| 700 | 1 | _ | |a Blockley-Powell, Storm K |0 0009-0009-8519-9904 |b 38 |
| 700 | 1 | _ | |a Haeusler, Rebecca A |0 0000-0002-6973-9845 |b 39 |
| 700 | 1 | _ | |a Steinman, Jonathan B |b 40 |
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| 700 | 1 | _ | |a Monga, Satdarshan P |0 0000-0002-8437-3378 |b 42 |
| 700 | 1 | _ | |a Bataller, Ramon |b 43 |
| 700 | 1 | _ | |a Masoodi, Mojgan |b 44 |
| 700 | 1 | _ | |a Arpaia, Nicholas |0 0000-0002-0657-0528 |b 45 |
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