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000299785 1001_ $$00000-0003-3311-2562$$aSugimoto, Atsushi$$b0
000299785 245__ $$aHepatic stellate cells control liver zonation, size and functions via R-spondin 3.
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000299785 520__ $$aHepatic stellate cells (HSCs) have a central pathogenetic role in the development of liver fibrosis. However, their fibrosis-independent and homeostatic functions remain poorly understood1-5. Here we demonstrate that genetic depletion of HSCs changes WNT activity and zonation of hepatocytes, leading to marked alterations in liver regeneration, cytochrome P450 metabolism and injury. We identify R-spondin 3 (RSPO3), an HSC-enriched modulator of WNT signalling, as responsible for these hepatocyte-regulatory effects of HSCs. HSC-selective deletion of Rspo3 phenocopies the effects of HSC depletion on hepatocyte gene expression, zonation, liver size, regeneration and cytochrome P450-mediated detoxification, and exacerbates alcohol-associated and metabolic dysfunction-associated steatotic liver disease. RSPO3 expression decreases with HSC activation and is inversely associated with outcomes in patients with alcohol-associated and metabolic dysfunction-associated steatotic liver disease. These protective and hepatocyte-regulating functions of HSCs via RSPO3 resemble the R-spondin-expressing stromal niche in other organs and should be integrated into current therapeutic concepts.
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000299785 7001_ $$00000-0002-0624-0449$$aSaito, Yoshinobu$$b1
000299785 7001_ $$0P:(DE-He78)8e8c59b5f06ec6da46af280f37a413c0$$aWang, Guanxiong$$b2$$eFirst author$$udkfz
000299785 7001_ $$aSun, Qiuyan$$b3
000299785 7001_ $$aYin, Chuan$$b4
000299785 7001_ $$0P:(DE-He78)5db788041043691b6a2f18e8ba5c73ae$$aLee, Ki Hong$$b5$$udkfz
000299785 7001_ $$aGeng, Yana$$b6
000299785 7001_ $$00000-0003-2184-7238$$aRajbhandari, Presha$$b7
000299785 7001_ $$aHernandez, Celine$$b8
000299785 7001_ $$00000-0002-7439-7851$$aSteffani, Marcella$$b9
000299785 7001_ $$aQie, Jingran$$b10
000299785 7001_ $$00000-0002-6618-2973$$aSavage, Thomas$$b11
000299785 7001_ $$00009-0007-6454-2158$$aGoyal, Dhruv M$$b12
000299785 7001_ $$aRay, Kevin C$$b13
000299785 7001_ $$aNeelakantan, Taruna V$$b14
000299785 7001_ $$aYin, Deqi$$b15
000299785 7001_ $$00000-0002-5410-6586$$aMelms, Johannes$$b16
000299785 7001_ $$aLehrich, Brandon M$$b17
000299785 7001_ $$00000-0002-8482-0369$$aYasaka, Tyler M$$b18
000299785 7001_ $$aLiu, Silvia$$b19
000299785 7001_ $$aOertel, Michael$$b20
000299785 7001_ $$aLan, Tian$$b21
000299785 7001_ $$00000-0002-6002-9986$$aGuillot, Adrien$$b22
000299785 7001_ $$aPeiseler, Moritz$$b23
000299785 7001_ $$00000-0002-1345-8147$$aFilliol, Aveline$$b24
000299785 7001_ $$aKanzaki, Hiroaki$$b25
000299785 7001_ $$aFujiwara, Naoto$$b26
000299785 7001_ $$00000-0002-6731-734X$$aRavi, Samhita$$b27
000299785 7001_ $$00000-0003-2379-6702$$aIzar, Benjamin$$b28
000299785 7001_ $$aBrosch, Mario$$b29
000299785 7001_ $$aHampe, Jochen$$b30
000299785 7001_ $$aRemotti, Helen$$b31
000299785 7001_ $$00000-0003-1696-7753$$aArgemi, Josepmaria$$b32
000299785 7001_ $$aSun, Zhaoli$$b33
000299785 7001_ $$00000-0002-4174-2786$$aKendall, Timothy J$$b34
000299785 7001_ $$00000-0001-9430-1426$$aHoshida, Yujin$$b35
000299785 7001_ $$00000-0001-6206-0226$$aTacke, Frank$$b36
000299785 7001_ $$00000-0002-5741-1471$$aFallowfield, Jonathan A$$b37
000299785 7001_ $$00009-0009-8519-9904$$aBlockley-Powell, Storm K$$b38
000299785 7001_ $$00000-0002-6973-9845$$aHaeusler, Rebecca A$$b39
000299785 7001_ $$aSteinman, Jonathan B$$b40
000299785 7001_ $$aPajvani, Utpal B$$b41
000299785 7001_ $$00000-0002-8437-3378$$aMonga, Satdarshan P$$b42
000299785 7001_ $$aBataller, Ramon$$b43
000299785 7001_ $$aMasoodi, Mojgan$$b44
000299785 7001_ $$00000-0002-0657-0528$$aArpaia, Nicholas$$b45
000299785 7001_ $$aLee, Youngmin A$$b46
000299785 7001_ $$00000-0002-3532-3868$$aStockwell, Brent R$$b47
000299785 7001_ $$0P:(DE-He78)2e92d0ae281932fc7347d819fec36b0b$$aAugustin, Hellmut$$b48$$udkfz
000299785 7001_ $$00000-0003-4571-2098$$aSchwabe, Robert F$$b49
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