Highlight report: liver regeneration by a subset of hepatocytes with high expression of telomerase

  • Patrick NellEmail author
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The author declares that he has no conflict of interest.


  1. Albrecht W, Kappenberg F, Brecklinghaus T, Gardner I, Rahnenführer J, Hengstler JG (2019) Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations. Arch Toxicol 93(6):1609–1637. CrossRefPubMedGoogle Scholar
  2. Bolt HM (2017) Highlight report: the pseudolobule in liver fibrosis. EXCLI J 16:1321–1322PubMedPubMedCentralGoogle Scholar
  3. Calado RT, Brudno J, Mehta P, Chanock SJ, Boyer TD, Young NS (2011) Constitutional telomerase mutations are genetic risk factors for cirrhosis. Hepatology 53(5):1600–1607. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Drasdo D, Hoehme S, Hengstler JG (2014) How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis. J Hepatol 61(4):951–956. CrossRefPubMedGoogle Scholar
  5. Frey O, Misun PM, Fluri DA, Hengstler JG, Hierlemann A (2014) Reconfigurable microfluidic hanging drop network for multi-tissue interaction and analysis. Nat Commun 5:4250. CrossRefPubMedGoogle Scholar
  6. Ghallab A (2017) Highlight report: Monitoring cytochrome P450 activities in living hepatocytes. EXCLI J 16:1330–1331PubMedPubMedCentralGoogle Scholar
  7. Ghallab A, Cellière G, Henkel SG, Drasdo D, Gebhardt R, Hengstler JG (2016) Model-guided identification of a therapeutic strategy to reduce hyperammonemia in liver diseases. J Hepatol 64(4):860–871. CrossRefPubMedGoogle Scholar
  8. Godoy P, Hewitt NJ, Albrecht U, Xu JJ, Yarborough KM, Hengstler JG (2013) Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Arch Toxicol 87(8):1315–1530CrossRefPubMedPubMedCentralGoogle Scholar
  9. Godoy P, Schmidt-Heck W, Natarajan K, Küppers-Munther B, Hay DC, Hengstler JG (2016a) Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells. J Hepatol. 63(4):934–942CrossRefGoogle Scholar
  10. Godoy P, Widera A, Schmidt-Heck W, Blüthgen N, Dooley S, Hengstler JG (2016b) Gene network activity in cultivated primary hepatocytes is highly similar to diseased mammalian liver tissue. Arch Toxicol 90(10):2513–2529CrossRefPubMedPubMedCentralGoogle Scholar
  11. Godoy P, Schmidt-Heck W, Hellwig B, Walter J, Blüthgen N, Hengstler JG (2018) Assessment of stem cell differentiation based on genome-wide expression profiles. Philos Trans R Soc Lond B Biol Sci 373(1750):20170221. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Grinberg M, Stöber RM, Edlund K, Leist M, Rahnenführer J, Hengstler JG (2014) Toxicogenomics directory of chemically exposed human hepatocytes. Arch Toxicol 88(12):2261–2287CrossRefPubMedGoogle Scholar
  13. Grinberg M, Stöber RM, Albrecht W, Ellinger-Ziegelbauer H, Rahnenführer J, Hengstler JG (2018) Toxicogenomics directory of rat hepatotoxicants in vivo and in cultivated hepatocytes. Arch Toxicol 92(12):3517–3533. CrossRefPubMedGoogle Scholar
  14. Gu X, Albrecht W, Edlund K, Han B, Hengstler JG, Stoeber R (2018) Relevance of the incubation period in cytotoxicity testing with primary human hepatocytes. Arch Toxicol 92(12):3505–3515. CrossRefPubMedGoogle Scholar
  15. Hammad S, Hoehme S, Friebel A, Gebhardt R, Drasdo D, Hengstler JG (2014) Protocols for staining of bile canalicular and sinusoidal networks of human, mouse and pig livers, three-dimensional reconstruction and quantification of tissue microarchitecture by image processing and analysis. Arch Toxicol 88(5):1161–1183CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hartmann D, Srivastava U, Thaler M, Manns MP, Beaugrand M, Rudolph KL (2011) Telomerase gene mutations are associated with cirrhosis formation. Hepatology 53(5):1608–1617. CrossRefPubMedGoogle Scholar
  17. Hoehme S, Brulport M, Bauer A, Timmel T, Hengstler JG, Drasdo D (2010) Prediction and validation of cell alignment along microvessels as order principle to restore tissue architecture in liver regeneration. Proc Natl Acad Sci USA 107(23):10371–10376. CrossRefPubMedGoogle Scholar
  18. Hoehme S, Friebel A, Hammad S, Drasdo D, Hengstler JG (2017) Creation of three-dimensional liver tissue models from experimental images for systems medicine. Methods Mol Biol 1506:319–362CrossRefPubMedGoogle Scholar
  19. Hoehme S, Bertaux F, Weens W, Grasl-Kraupp B, Hengstler JG, Drasdo D (2018) Model prediction and validation of an order mechanism controlling the spatiotemporal phenotype of early hepatocellular carcinoma. Bull Math Biol 80(5):1134–1171. CrossRefPubMedGoogle Scholar
  20. Jansen PL, Ghallab A, Vartak N, Schaap FG, Hampe J, Hengstler JG (2017) The ascending pathophysiology of cholestatic liver disease. Hepatology 65(2):722–738CrossRefPubMedGoogle Scholar
  21. Kim JY, Fluri DA, Marchan R, Kelm JM, Hierlemann A, Frey O (2015) 3D spherical microtissues and microfluidic technology for multi-tissue experiments and analysis. J Biotechnol 10(205):24–35. CrossRefGoogle Scholar
  22. Leist M, Ghallab A, Graepel R, Kroese D, van de Water B, Hengstler JG (2017) Adverse outcome pathways: opportunities, limitations and open questions. Arch Toxicol 91(11):3477–3505. CrossRefPubMedGoogle Scholar
  23. Lin S, Nascimento EM, Gajera CR, Garbuzov A, Wang S, Artandi SE (2018) Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury. Nature 556(7700):244–248. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Malato Y, Naqvi S, Schürmann N, Kay MA, Grimm D, Willenbring H (2011) Fate tracing of mature hepatocytes in mouse liver homeostasis and regeneration. J Clin Invest 121(12):4850–4860. CrossRefPubMedPubMedCentralGoogle Scholar
  25. Raven A, Lu WY, Man TY, -Constant C, Boulter L, Forbes SJ (2017) Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration. Nature 547(7663):350–354. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Rudolph KL, Chang S, Millard M, Agus N, DePinho RA (2000) Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery. Science 287(5456):1253–1258CrossRefPubMedGoogle Scholar
  27. Sachinidis A, Albrecht W, Nell P, Hewitt NJ, Edlund K, Hengstler JG (2019) Road Map for development of stem cell-based alternative test methods. Trends Mol Med 25(6):470–481. CrossRefPubMedGoogle Scholar
  28. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Sezgin S, Hassan R, Zühlke S, Hengstler JG, Spiteller M, Ghallab A (2018) Spatio-temporal visualization of the distribution of acetaminophen as well as its metabolites and adducts in mouse livers by MALDI MSI. Arch Toxicol 92(9):2963–2977CrossRefPubMedGoogle Scholar
  30. Tarlow BD, Finegold MJ, Grompe M (2014a) Clonal tracing of Sox9+ liver progenitors in mouse oval cell injury. Hepatology 60(1):278–289. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Tarlow BD, Pelz C, Naugler WE, Wilson EM, Finegold MJ, Grompe M (2014b) Bipotential adult liver progenitors are derived from chronically injured mature hepatocytes. Cell Stem Cell 15(5):605–618CrossRefPubMedPubMedCentralGoogle Scholar
  32. Vartak N, Damle-Vartak A, Richter B, Dirsch O, Dahmen U, Hammad S, Hengstler JG (2016) Cholestasis-induced adaptive remodeling of interlobular bile ducts. Hepatology 63(3):951–964. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Yanger K, Knigin D, Zong Y, 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. CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Leibniz Research Centre for Working Environment and Human FactorsDortmundGermany

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