biostudies-literatureSong PNational Natural Science Foundation of ChinaNational Key Research and Development Program of Chinae346https://www.ebi.ac.uk/biostudies/studies/S-EPMC10442476biostudies-literatureUnknown4(5)Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single-cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti-inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the MedCommCellular senescence primes liver fibrosis regression through Notch-EZH2.PMC104424768232500781770560814220092016YFA01021002021YFA1100500He FXu MLiu JJTao KSDu WLing YWDing JXu HWang LSong PFang ZQDuan JLLi ZWfalseCellular senescence primes liver fibrosis regression through Notch-EZH2.Cellular senescence plays a pivotal role in wound healing. At the initiation of liver fibrosis regression, accumulated senescent cells were detected and genes of senescence were upregulated. Flow cytometry combined with single-cell RNA sequencing analyses revealed that most of senescent cells were liver nonparenchymal cells. Removing senescent cells by dasatinib and quercetin (DQ), alleviated hepatic cellular senescence, impeded fibrosis regression, and disrupted liver sinusoids. Clearance of senescent cells not only decreased senescent macrophages but also shrank the proportion of anti-inflammatory M2 macrophages through apoptotic pathway. Subsequently, macrophages were depleted by clodronate, which diminished hepatic senescent cells and impaired fibrosis regression. Mechanistically, the 2023-01-01T00:00:00Z2023 Oct2026-06-04T08:06:54.185Z2025-04-06T11:53:59.467ZS-EPMC104424763761496510.1002/mco2.346