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@ARTICLE{Lim:298936,
      author       = {B. Lim$^*$ and A. Kamal and B. Gomez Ramos$^*$ and J.
                      Adrian Segarra$^*$ and I. L. Ibarra and L. Dignas$^*$ and T.
                      Kindinger$^*$ and K. Volz$^*$ and M. Rahbari$^*$ and N.
                      Rahbari and E. Poisel$^*$ and K. Kafetzopoulou$^*$ and L.
                      Böse$^*$ and M. Breinig$^*$ and D. Heide$^*$ and S. U.
                      Gallage$^*$ and J. E. Barragan Avila$^*$ and H. Wiethoff and
                      I. Berest and S. Schnabellehner and M. Schneider$^*$ and J.
                      Becker$^*$ and D. Helm$^*$ and D. Grimm and T. Mäkinen and
                      D. F. Tschaharganeh$^*$ and M. Heikenwalder$^*$ and J. B.
                      Zaugg and M. Mall$^*$},
      title        = {{A}ctive repression of cell fate plasticity by {PROX}1
                      safeguards hepatocyte identity and prevents liver
                      tumorigenesis.},
      journal      = {Nature genetics},
      volume       = {57},
      number       = {3},
      issn         = {1061-4036},
      address      = {London},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DKFZ-2025-00370},
      pages        = {668-679},
      year         = {2025},
      note         = {DKFZ-ZMBH Alliance /#EA:A340#LA:A340# / 2025
                      Mar;57(3):668-679},
      abstract     = {Cell fate plasticity enables development, yet unlocked
                      plasticity is a cancer hallmark. While transcription master
                      regulators induce lineage-specific genes to restrict
                      plasticity, it remains unclear whether plasticity is
                      actively suppressed by lineage-specific repressors. Here we
                      computationally predict so-called safeguard repressors for
                      18 cell types that block phenotypic plasticity lifelong. We
                      validated hepatocyte-specific candidates using
                      reprogramming, revealing that prospero homeobox protein 1
                      (PROX1) enhanced hepatocyte identity by direct repression of
                      alternative fate master regulators. In mice, Prox1 was
                      required for efficient hepatocyte regeneration after injury
                      and was sufficient to prevent liver tumorigenesis. In line
                      with patient data, Prox1 depletion caused hepatocyte fate
                      loss in vivo and enabled the transition of hepatocellular
                      carcinoma to cholangiocarcinoma. Conversely, overexpression
                      promoted cholangiocarcinoma to hepatocellular carcinoma
                      transdifferentiation. Our findings provide evidence for
                      PROX1 as a hepatocyte-specific safeguard and support a model
                      where cell-type-specific repressors actively suppress
                      plasticity throughout life to safeguard lineage identity and
                      thus prevent disease.},
      cin          = {A340 / F190 / D440 / W120},
      ddc          = {570},
      cid          = {I:(DE-He78)A340-20160331 / I:(DE-He78)F190-20160331 /
                      I:(DE-He78)D440-20160331 / I:(DE-He78)W120-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39948437},
      doi          = {10.1038/s41588-025-02081-w},
      url          = {https://inrepo02.dkfz.de/record/298936},
}