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Hepatocytes pp 71–82Cite as

Induction of Bile Canaliculi-Forming Hepatocytes from Human Pluripotent Stem Cells

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 2544))

Abstract

Cell polarity and formation of bile canaliculi can be achieved in hepatocytes which are generated from patient-derived induced pluripotent stem cells. This allows for the study of endogenous mutant proteins, patient-specific pathogenesis, and drug responses for diseases where hepatocyte polarity and bile canaliculi play a key role. Here, we describe a step-by-step protocol for the generation of bile canaliculi-forming hepatocytes from induced pluripotent stem cells and their evaluation.

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References

  1. Treyer A, Müsch A (2013) Hepatocyte polarity. Compr Physiol 3:243–287. https://doi.org/10.1002/cphy.c120009

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gissen P, Arias IM (2015) Structural and functional hepatocyte polarity and liver disease. J Hepatol 63:1023–1037. https://doi.org/10.1016/j.jhep.2015.06.015

    Article  PubMed  PubMed Central  Google Scholar 

  3. Li Q, Sun Y, SCD v IJ (2021) A link between intrahepatic cholestasis and genetic variations in intracellular trafficking regulators. Biology (Basel) 10:119. https://doi.org/10.3390/biology10020119

    Article  CAS  Google Scholar 

  4. Bull LN, Thompson RJ (2018) Progressive familial intrahepatic cholestasis. Clin Liver Dis 22:657–669. https://doi.org/10.1016/j.cld.2018.06.003

    Article  PubMed  Google Scholar 

  5. Jacquemin E (2012) Progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol 36(Suppl 1):S26–S35. https://doi.org/10.1016/S2210-7401(12)70018-9

    Article  CAS  PubMed  Google Scholar 

  6. Shah AB, Chernov I, Zhang HT et al (1997) Identification and analysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-phenotype correlation, and functional analyses. Am J Hum Genet 61:317–328. https://doi.org/10.1086/514864

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Martinelli D, Travaglini L, Drouin CA et al (2013) MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. Brain 136:872–881. https://doi.org/10.1093/brain/awt012

    Article  PubMed  Google Scholar 

  8. Koivisto UM, Hubbard AL, Mellman I (2001) A novel cellular phenotype for familial hypercholesterolemia due to a defect in polarized targeting of LDL receptor. Cell 105:575–585. https://doi.org/10.1016/s0092-8674(01)00371-3

    Article  CAS  PubMed  Google Scholar 

  9. van der Woerd WL, Houwen RH, van de Graaf SF (2017) Current and future therapies for inherited cholestatic liver diseases. World J Gastroenterol 23:763–775. https://doi.org/10.3748/wjg.v23.i5.763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Amzal R, Thébaut A, Lapalus M et al (2020) Pharmacological premature termination codon readthrough of ABCB11 in bile salt export pump deficiency: an in vitro study. Hepatology (Baltimore, Md). https://doi.org/10.1002/hep.31476

  11. Matakovic L, Li Q, van IJzendoorn SCD (2020) Letter to the editor – Liver cell models for premature termination codon readthrough analyses. Hepatology. https://doi.org/10.1002/hep.31682

  12. Mareux E, Lapalus M, Amzal R et al (2020) Functional rescue of an ABCB11 mutant by ivacaftor: a new targeted pharmacotherapy approach in bile salt export pump deficiency. Liver Int 40:1917–1925. https://doi.org/10.1111/liv.14518

    Article  CAS  PubMed  Google Scholar 

  13. Si-Tayeb K, Noto FK, Nagaoka M et al (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51:297–305. https://doi.org/10.1002/hep.23354

    Article  CAS  PubMed  Google Scholar 

  14. Song Z, Cai J, Liu Y, Zhao D, Yong J, Duo S, Song X, Guo Y, Zhao Y, Qin H, Yin X, Wu C, Che J, Lu S, Ding M, Deng H et al (2009) Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res 19(11):1233. https://pubmed.ncbi.nlm.nih.gov/19736565/. Accessed 10 Mar 2021

    Article  PubMed  Google Scholar 

  15. Overeem AW, Klappe K, Parisi S et al (2019) Pluripotent stem cell-derived bile canaliculi-forming hepatocytes to study genetic liver diseases involving hepatocyte polarity. J Hepatol 71:344–356. https://doi.org/10.1016/j.jhep.2019.03.031

    Article  PubMed  Google Scholar 

  16. Parisi S, Polishchuk EV, Allocca S et al (2018) Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells. Sci Rep 8:6247. https://doi.org/10.1038/s41598-018-24717-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Katagami Y, Kondo T, Suga M et al (2020) Generation of a human induced pluripotent stem cell line, BRCi009-A, derived from a patient with glycogen storage disease type 1a. Stem Cell Res 49:102095. https://doi.org/10.1016/j.scr.2020.102095

    Article  CAS  PubMed  Google Scholar 

  18. Caron J, Pène V, Tolosa L et al (2019) Low-density lipoprotein receptor-deficient hepatocytes differentiated from induced pluripotent stem cells allow familial hypercholesterolemia modeling, CRISPR/Cas-mediated genetic correction, and productive hepatitis C virus infection. Stem Cell Res Ther 10:221. https://doi.org/10.1186/s13287-019-1342-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Omer L, Hudson EA, Zheng S et al (2017) CRISPR correction of a homozygous low-density lipoprotein receptor mutation in familial hypercholesterolemia induced pluripotent stem cells. Hepatol Commun 1:886–898. https://doi.org/10.1002/hep4.1110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Imagawa K, Takayama K, Isoyama S et al (2017) Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells. Sci Rep 7:41806. https://doi.org/10.1038/srep41806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Török G, Erdei Z, Lilienberg J et al (2020) The importance of transporters and cell polarization for the evaluation of human stem cell-derived hepatic cells. PLoS One 15:e0227751. https://doi.org/10.1371/journal.pone.0227751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mee CJ, Harris HJ, Farquhar MJ et al (2009) Polarization restricts hepatitis C virus entry into HepG2 hepatoma cells. J Virol 83:6211–6221. https://doi.org/10.1128/JVI.00246-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Mee CJ, Farquhar MJ, Harris HJ et al (2010) Hepatitis C virus infection reduces hepatocellular polarity in a vascular endothelial growth factor-dependent manner. Gastroenterology 138:1134–1142. https://doi.org/10.1053/j.gastro.2009.11.047

    Article  CAS  PubMed  Google Scholar 

  24. Capelli N, Marion O, Dubois M et al (2019) Vectorial release of hepatitis E virus in polarized human hepatocytes. J Virol 93. https://doi.org/10.1128/JVI.01207-18

  25. Madigan VJ, Tyson TO, Yuziuk JA et al (2019) A CRISPR screen identifies the cell polarity determinant crumbs 3 as an adeno-associated virus restriction factor in hepatocytes. J Virol 93. https://doi.org/10.1128/JVI.00943-19

  26. Dao Thi VL, Wu X, Belote RL et al (2020) Stem cell-derived polarized hepatocytes. Nat Commun 11:1677. https://doi.org/10.1038/s41467-020-15337-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Slim CL, van IJzendoorn SCD, Lázaro-Diéguez F, Müsch A (2014) The special case of hepatocytes: unique tissue architecture calls for a distinct mode of cell division. Bioarchitecture 4:47–52. https://doi.org/10.4161/bioa.29012

    Article  PubMed  PubMed Central  Google Scholar 

  28. Müsch A (2014) The unique polarity phenotype of hepatocytes. Exp Cell Res 328:276–283. https://doi.org/10.1016/j.yexcr.2014.06.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Scholich A, Syga S, Morales-Navarrete H et al (2020) Quantification of nematic cell polarity in three-dimensional tissues. PLoS Comput Biol 16. https://doi.org/10.1371/journal.pcbi.1008412

  30. Miyajima A, Kinoshita T, Tanaka M et al (2000) Role of Oncostatin M in hematopoiesis and liver development. Cytokine Growth Factor Rev 11:177–183. https://doi.org/10.1016/s1359-6101(00)00003-4

    Article  CAS  PubMed  Google Scholar 

  31. Kamiya A, Kinoshita T, Ito Y et al (1999) Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J 18:2127–2136. https://doi.org/10.1093/emboj/18.8.2127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. van der Wouden JM, van IJzendoorn SCD, Hoekstra D (2002) Oncostatin M regulates membrane traffic and stimulates bile canalicular membrane biogenesis in HepG2 cells. EMBO J 21:6409–6418. https://doi.org/10.1093/emboj/cdf629

    Article  PubMed  PubMed Central  Google Scholar 

  33. Van IJzendoorn SCD, Théard D, Van Der Wouden JM et al (2004) Oncostatin M-stimulated apical plasma membrane biogenesis requires p27(Kip1)-regulated cell cycle dynamics. Mol Biol Cell 15:4105–4114. https://doi.org/10.1091/mbc.e04-03-0201

    Article  PubMed  PubMed Central  Google Scholar 

  34. Berthiaume F, Moghe PV, Toner M, Yarmush ML (1996) Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: hepatocytes cultured in a sandwich configuration. FASEB J 10:1471–1484. https://doi.org/10.1096/fasebj.10.13.8940293

    Article  CAS  PubMed  Google Scholar 

  35. Dunn JC, Yarmush ML, Koebe HG, Tompkins RG (1989) Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB J 3:174–177. https://doi.org/10.1096/fasebj.3.2.2914628

    Article  CAS  PubMed  Google Scholar 

  36. Deharde D, Schneider C, Hiller T et al (2016) Bile canaliculi formation and biliary transport in 3D sandwich-cultured hepatocytes in dependence of the extracellular matrix composition. Arch Toxicol 90:2497–2511. https://doi.org/10.1007/s00204-016-1758-z

    Article  CAS  PubMed  Google Scholar 

  37. Luce E, Dubart-Kupperschmitt A (2020) Pluripotent stem cell-derived cholangiocytes and cholangiocyte organoids. Methods Cell Biol 159:69–93. https://doi.org/10.1016/bs.mcb.2020.03.011

    Article  CAS  PubMed  Google Scholar 

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Author information

Author notes

  1. Lavinija Matakovic, Arend W. Overeem and Sven C. D. van IJzendoorn have equally contributed in this chapter.

Authors and Affiliations

  1. Department of Biomedical Sciences of Cells and Systems, section Molecular Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

    Lavinija Matakovic, Arend W. Overeem, Karin Klappe & Sven C. D. van IJzendoorn

  2. Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands

    Arend W. Overeem

Authors
  1. Lavinija Matakovic
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  2. Arend W. Overeem
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  3. Karin Klappe
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  4. Sven C. D. van IJzendoorn
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Corresponding author

Correspondence to Sven C. D. van IJzendoorn .

Editor information

Editors and Affiliations

  1. Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine, Sapporo, Hokkaido, Japan

    Naoki Tanimizu

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Matakovic, L., Overeem, A.W., Klappe, K., van IJzendoorn, S.C.D. (2022). Induction of Bile Canaliculi-Forming Hepatocytes from Human Pluripotent Stem Cells. In: Tanimizu, N. (eds) Hepatocytes. Methods in Molecular Biology, vol 2544. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2557-6_4

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  • DOI: https://doi.org/10.1007/978-1-0716-2557-6_4

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2556-9

  • Online ISBN: 978-1-0716-2557-6

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