Project description:Using snRNA-seq combined with spatial profiling of healthy and ALF explant human livers, we uncover a novel migratory hepatocyte subpopulation. We discover a corollary subpopulation in a mouse model of APAP-induced liver regeration, and demonstrate that this subpopulation meidates wound closure following liver injury.

2023-02-01 | GSE223558 | GEO

Multimodal decoding of human liver regeneration [snrna_human]

2023-02-01 | GSE223581 | GEO

Multimodal decoding of human liver regeneration [st_mouse]

2023-02-01 | GSE223560 | GEO

Multimodal decoding of human liver regeneration [st_human]

2023-02-01 | GSE223559 | GEO

Multimodal decoding of human liver regeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-01 | GSE223561 | GEO

Mouse liver regeneration quantitative proteomics

Project description:The liver is the only organ in mammals, which fully regenerates after injury. To identify novel regulators of liver regeneration, we performed quantitative large-scale proteomics analysis of subcellular fractions from normal versus regenerating mouse liver. Proteins of the ubiquitin-proteasome pathway were rapidly regulated by partial hepatectomy, with the ubiquitin ligase Nedd4-1 being among the top hits. Knock-down of Nedd4-1 in hepatocytes in vivo through nanoparticle-mediated delivery of siRNA caused severe liver damage after partial hepatectomy and impaired regeneration, resulting in liver failure. Mechanistically, we demonstrate that Nedd4-1 is required for efficient activation of Erk1/2 signaling by receptor tyrosine kinases involved in liver regeneration through inhibition of receptor internalization, thus controlling a major pro-mitogenic and cytoprotective signaling pathway in the regenerating liver. These results highlight the power of large-scale proteomics to identify key players in liver regeneration and the importance of posttranslational regulation of growth factor signaling in this process.

2017-09-13 | PXD004108 | Pride

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