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@ARTICLE{FalickMichaeli:306269,
      author       = {T. Falick Michaeli and O. Sabag and B. Azria and R. Fok and
                      N. Abudi and R. Abramovitch and J. Monin and Y. Gielchinsky
                      and H. Cedar and Y. Bergman},
      title        = {{H}epatocyte regeneration is driven by embryo-like {DNA}
                      methylation reprogramming.},
      journal      = {Proceedings of the National Academy of Sciences of the
                      United States of America},
      volume       = {121},
      number       = {16},
      issn         = {0027-8424},
      address      = {Washington, DC},
      publisher    = {National Acad. of Sciences},
      reportid     = {DKFZ-2025-02495},
      pages        = {e2314885121},
      year         = {2024},
      note         = {#DKFZ-MOST-Ca200#},
      abstract     = {As a result of partial hepatectomy, the remaining liver
                      tissue undergoes a process of renewed proliferation that
                      leads to rapid regeneration of the liver. By following the
                      early stages of this process, we observed dramatic
                      programmed changes in the DNA methylation profile,
                      characterized by both de novo and demethylation events, with
                      a subsequent return to the original adult pattern as the
                      liver matures. Strikingly, these transient alterations
                      partially mimic the DNA methylation state of embryonic
                      hepatoblasts (E16.5), indicating that hepatocytes actually
                      undergo epigenetic dedifferentiation. Furthermore,
                      Tet2/Tet3-deletion experiments demonstrated that these
                      changes in methylation are necessary for carrying out basic
                      embryonic functions, such as proliferation, a key step in
                      liver regeneration. This implies that unlike tissue-specific
                      regulatory regions that remain demethylated in the adult,
                      early embryonic genes are programmed to first undergo
                      demethylation, followed by remethylation as development
                      proceeds. The identification of this built-in system may
                      open targeting opportunities for regenerative medicine.},
      keywords     = {DNA Methylation / Embryo, Mammalian: metabolism /
                      Hepatocytes / DNA methylation (Other) / dedifferentiation
                      (Other) / partial hepatectomy (Other)},
      ddc          = {500},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38588413},
      pmc          = {pmc:PMC11032470},
      doi          = {10.1073/pnas.2314885121},
      url          = {https://inrepo02.dkfz.de/record/306269},
}