Volume 9 Issue 6
Dec.  2023
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Xingrui Wang, Wenjuan Pu, Huan Zhu, Mingjun Zhang, Bin Zhou. Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion. Biophysics Reports, 2023, 9(6): 309-324. doi: 10.52601/bpr.2023.230034
Citation: Xingrui Wang, Wenjuan Pu, Huan Zhu, Mingjun Zhang, Bin Zhou. Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion. Biophysics Reports, 2023, 9(6): 309-324. doi: 10.52601/bpr.2023.230034

Establishment of a Fah-LSL mouse model to study BEC-to-hepatocyte conversion

doi: 10.52601/bpr.2023.230034
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  • Corresponding author: zhoubin@sibs.ac.cn (B. Zhou)
  • Received Date: 07 November 2023
  • Accepted Date: 22 January 2024
  • Available Online: 05 March 2024
  • Publish Date: 01 December 2023
  • The liver consists predominantly of hepatocytes and biliary epithelial cells (BECs), which serve distinct physiological functions. Although hepatocytes primarily replenish their own population during homeostasis and injury repair, recent findings have suggested that BECs can transdifferentiate into hepatocytes when hepatocyte-mediated liver regeneration is impaired. However, the cellular and molecular mechanisms governing this BEC-to-hepatocyte conversion remain poorly understood largely because of the inefficiency of existing methods for inducing lineage conversion. Therefore, this study introduces a novel mouse model engineered by the Zhou's lab, where hepatocyte senescence is induced by the deletion of the fumarylacetoacetate (Fah) gene. This model facilitates the efficient conversion of BECs to hepatocytes and allows for the simultaneous lineage tracing of BECs; consequently, a transitional liver progenitor cell population can be identified during lineage conversion. This study also outlines the technical procedures for utilizing this model to determine the underlying cellular and molecular mechanisms of BEC-to-hepatocyte conversion and provides new insights into liver regeneration and its underlying molecular mechanism.

  • The authors declare that they have no conflicts of interest.
    All institutional and national guidelines for the care and use of laboratory animals were followed.

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  • Deng X, Zhang X, Li W, Feng RX, Li L, Yi GR, Zhang XN, Yin C, Yu HY, Zhang JP, Lu B, Hui L, Xie WF (2018) Chronic liver injury induces conversion of biliary epithelial cells into hepatocytes. Cell Stem Cell 23(1): 114−122.e113 doi: 10.1016/j.stem.2018.05.022
    Español-Suñer R, Carpentier R, Van Hul N, Legry V, Achouri Y, Cordi S, Jacquemin P, Lemaigre F, Leclercq IA (2012) Liver progenitor cells yield functional hepatocytes in response to chronic liver injury in mice. Gastroenterology 143(6): 1564−1575.e1567 doi: 10.1053/j.gastro.2012.08.024
    Gadd VL, Aleksieva N, Forbes SJ (2020) Epithelial plasticity during liver injury and regeneration. Cell Stem Cell 27(4): 557−573 doi: 10.1016/j.stem.2020.08.016
    Grompe M, al-Dhalimy M, Finegold M, Ou CN, Burlingame T, Kennaway NG, Soriano P (1993) Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice. Genes Dev 7(12a): 2298−2307 doi: 10.1101/gad.7.12a.2298
    Han X, Wang Y, Pu W, Huang X, Qiu L, Li Y, Yu W, Zhao H, Liu X, He L, Zhang L, Ji Y, Lu J, Lui KO, Zhou B (2019) Lineage tracing reveals the bipotency of SOX9(+) hepatocytes during liver regeneration. Stem Cell Reports 12(3): 624−638 doi: 10.1016/j.stemcr.2019.01.010
    Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ, Jones AR, Lein ES, Zeng H (2010) A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci 13(1): 133−140 doi: 10.1038/nn.2467
    Means AL, Xu Y, Zhao A, Ray KC, Gu G (2008) A CK19(CreERT) knockin mouse line allows for conditional DNA recombination in epithelial cells in multiple endodermal organs. Genesis 46(6): 318−323 doi: 10.1002/dvg.20397
    Michalopoulos GK (2007) Liver regeneration. J Cell Physiol 213(2): 286−300 doi: 10.1002/jcp.21172
    Michalopoulos GK (2021) Novel insights into liver homeostasis and regeneration. Nat Rev Gastroenterol Hepatol 18(6): 369−370 doi: 10.1038/s41575-021-00454-0
    Michalopoulos GK, DeFrances MC (1997) Liver regeneration. Science 276(5309): 60−66 doi: 10.1126/science.276.5309.60
    Miyajima A, Tanaka M, Itoh T (2014) Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. Cell Stem Cell 14(5): 561−574 doi: 10.1016/j.stem.2014.04.010
    Nobili V, Jenkner A, Francalanci P, Castellano A, Holme E, Callea F, Dionisi-Vici C (2010) Tyrosinemia type 1: metastatic hepatoblastoma with a favorable outcome. Pediatrics 126(1): e235−238 doi: 10.1542/peds.2009-1639
    Pu W, Zhu H, Zhang M, Pikiolek M, Ercan C, Li J, Huang X, Han X, Zhang Z, Lv Z, Li Y, Liu K, He L, Liu X, Heim MH, Terracciano LM, Tchorz JS, Zhou B (2023) Bipotent transitional liver progenitor cells contribute to liver regeneration. Nat Genet 55(4): 651−664 doi: 10.1038/s41588-023-01335-9
    Raven A, Lu WY, Man TY, Ferreira-Gonzalez S, O'Duibhir E, Dwyer BJ, Thomson JP, Meehan RR, Bogorad R, Koteliansky V, Kotelevtsev Y, Ffrench-Constant C, Boulter L, Forbes SJ (2017) Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547(7663): 350−354 doi: 10.1038/nature23015
    Schaub JR, Malato Y, Gormond C, Willenbring H (2014) Evidence against a stem cell origin of new hepatocytes in a common mouse model of chronic liver injury. Cell Rep 8(4): 933−939 doi: 10.1016/j.celrep.2014.07.003
    Shin S, Upadhyay N, Greenbaum LE, Kaestner KH (2015) Ablation of Foxl1-Cre-labeled hepatic progenitor cells and their descendants impairs recovery of mice from liver injury. Gastroenterology 148(1): 192−202.e193 doi: 10.1053/j.gastro.2014.09.039
    Thakur A, Wong JCH, Wang EY, Lotto J, Kim D, Cheng JC, Mingay M, Cullum R, Moudgil V, Ahmed N, Tsai SH, Wei W, Walsh CP, Stephan T, Bilenky M, Fuglerud BM, Karimi MM, Gonzalez FJ, Hirst M, Hoodless PA (2019) Hepatocyte nuclear factor 4-alpha is essential for the active epigenetic state at enhancers in mouse liver. Hepatology 70(4): 1360−1376 doi: 10.1002/hep.30631
    Yanger K, Knigin D, Zong Y, Maggs L, Gu G, Akiyama H, Pikarsky E, Stanger BZ (2014) Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. Cell Stem Cell 15(3): 340−349 doi: 10.1016/j.stem.2014.06.003
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