Project description:We used AAV to overexpress ATF4 in murine cardiomyocytes in vivo and perfomred bioChIP-Seq to profile the chromatin occupancy of the exogenous protein
Project description:Liver zonation remains a critical aspect of understanding its response to acute injury. This study investigates the impact of acetaminophen-induced acute liver injury on zonal heterogeneity during early phases of injury. Through Ki67 staining, we observed a transient pause in proliferation specifically among mid-lobular hepatocytes during the initiation phase. Using spatial transcriptomics, immunostaining, and in vivo assays, we elucidated that mid-lobular hepatocytes upregulate the Atf4-Ddit3 axis, offering temporary protection at the cost of reduced proliferation mediated by Btg2. Our findings underscore the unique zonal metabolism of acetaminophen as a determinant of differential tissue responses across lobular regions. This study highlights how distinct liver zones exhibit varied responses during the early stages of acute injury, with mid-lobular hepatocytes showing an integrated stress response characterized by protective mechanisms that temporarily suppress proliferation.
Project description:Liver zonation remains a critical aspect of understanding its response to acute injury. This study investigates the impact of acetaminophen-induced acute liver injury on zonal heterogeneity during early phases of injury. Through Ki67 staining, we observed a transient pause in proliferation specifically among mid-lobular hepatocytes during the initiation phase. Using spatial transcriptomics, immunostaining, and in vivo assays, we elucidated that mid-lobular hepatocytes upregulate the Atf4-Ddit3 axis, offering temporary protection at the cost of reduced proliferation mediated by Btg2. Our findings underscore the unique zonal metabolism of acetaminophen as a determinant of differential tissue responses across lobular regions. This study highlights how distinct liver zones exhibit varied responses during the early stages of acute injury, with mid-lobular hepatocytes showing an integrated stress response characterized by protective mechanisms that temporarily suppress proliferation.
Project description:Identification of genes and functions regulated by DDIT3/GADD153/CHOP by transcriptional profiling of cell lines expressing high levels of tamoxifen induced DDIT3.
