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Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells

  • Authors:
    • Rong Li
    • Yang Zhao
    • Jeffrey J. Yourick
    • Robert L. Sprando
    • Xiugong Gao
  • View Affiliations / Copyright

    Affiliations: Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD 20708, USA, Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, U.S. Food and Drug Administration, Laurel, MD 20708, USA
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 43
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    Published online on: March 23, 2022
       https://doi.org/10.3892/br.2022.1526
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Abstract

Directed differentiation of human induced pluripotent stem cells (iPSCs) into hepatocytes could provide an unlimited source of liver cells, and therefore holds great promise for regenerative medicine, disease modeling, drug screening and toxicology studies. Various methods have been established during the past decade to differentiate human iPSCs into hepatocyte‑like cells (HLCs) using growth factors and/or small molecules. However, direct comparison of the differentiation efficiency and the quality of the final HLCs between different methods has rarely been reported. In the current study, two hepatocyte differentiation methods were devised, termed Method 1 and 2, through modifying existing well‑known hepatocyte differentiation strategies, and the resultant cells were compared phenotypically and functionally at different stages of hepatocyte differentiation. Compared to Method 1, higher differentiation efficiency and reproducibility were observed in Method 2, which generated highly homogeneous functional HLCs at the end of the differentiation process. The cells exhibited morphology closely resembling primary human hepatocytes and expressed high levels of hepatic protein markers. More importantly, these HLCs demonstrated several essential characteristics of mature hepatocytes, including major serum protein (albumin, fibronectin and α‑1 antitrypsin) secretion, urea release, glycogen storage and inducible cytochrome P450 activity. Further transcriptomic comparison of the HLCs derived from the two methods identified 1,481 differentially expressed genes (DEGs); 290 Gene Ontology terms in the biological process category were enriched by these genes, which were further categorized into 34 functional classes. Pathway analysis of the DEGs identified several signaling pathways closely involved in hepatocyte differentiation of pluripotent stem cells, including ‘signaling pathways regulating pluripotency of stem cells’, ‘Wnt signaling pathway’, ‘TGF‑beta signaling pathway’ and ‘PI3K‑Akt signaling pathway’. These results may provide a molecular basis for the differences observed between the two differentiation methods and suggest ways to further improve hepatocyte differentiation in order to obtain more mature HLCs for biomedical applications.
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1 

Shi Y, Inoue H, Wu JC and Yamanaka S: Induced pluripotent stem cell technology: A decade of progress. Nat Rev Drug Discov. 16:115–130. 2017.PubMed/NCBI View Article : Google Scholar

2 

Hannoun Z, Steichen C, Dianat N, Weber A and Dubart-Kupperschmitt A: The potential of induced pluripotent stem cell derived hepatocytes. J Hepatol. 65:182–199. 2016.PubMed/NCBI View Article : Google Scholar

3 

Kogiso T, Nagahara H, Otsuka M, Shiratori K and Dowdy SF: Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors. Hepatol Int. 7:937–944. 2013.PubMed/NCBI View Article : Google Scholar

4 

Pournasr B, Asghari-Vostikolaee MH and Baharvand H: Transcription factor-mediated reprograming of fibroblasts to hepatocyte-like cells. Eur J Cell Biol. 94:603–610. 2015.PubMed/NCBI View Article : Google Scholar

5 

Mallanna SK and Duncan SA: Differentiation of hepatocytes from pluripotent stem cells. Curr Protoc Stem Cell Biol. 26:1G.4.1–1G.4.13. 2013.PubMed/NCBI View Article : Google Scholar

6 

Song Z, Cai J, Liu Y, Zhao D, Yong J, Duo S, Song X, Guo Y, Zhao Y, Qin H, et al: Efficient generation of hepatocyte-like cells from human induced pluripotent stem cells. Cell Res. 19:1233–1242. 2009.PubMed/NCBI View Article : Google Scholar

7 

Szkolnicka D, Farnworth SL, Lucendo-Villarin B and Hay DC: Deriving functional hepatocytes from pluripotent stem cells. Curr Protoc Stem Cell Biol. 30:1G.5.1–12. 2014.PubMed/NCBI View Article : Google Scholar

8 

Siller R, Greenhough S, Naumovska E and Sullivan GJ: Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports. 4:939–952. 2015.PubMed/NCBI View Article : Google Scholar

9 

Du C, Feng Y, Qiu D, Xu Y, Pang M, Cai N, Xiang AP and Zhang Q: Highly efficient and expedited hepatic differentiation from human pluripotent stem cells by pure small-molecule cocktails. Stem Cell Res Ther. 9(58)2018.PubMed/NCBI View Article : Google Scholar

10 

Carpentier A, Nimgaonkar I, Chu V, Xia Y, Hu Z and Liang TJ: Hepatic differentiation of human pluripotent stem cells in miniaturized format suitable for high-throughput screen. Stem Cell Res. 16:640–650. 2016.PubMed/NCBI View Article : Google Scholar

11 

Wang Y, Alhaque S, Cameron K, Meseguer-Ripolles J, Lucendo-Villarin B, Rashidi H and Hay DC: Defined and scalable generation of hepatocyte-like cells from human pluripotent stem cells. J Vis Exp. (55355)2017.PubMed/NCBI View Article : Google Scholar

12 

Siller R and Sullivan GJ: Rapid screening of the endodermal differentiation potential of human pluripotent stem cells. Curr Protoc Stem Cell Biol. 43:1G.7.1–1G.7.23. 2017.PubMed/NCBI View Article : Google Scholar

13 

Corbett JL and Duncan SA: iPSC-derived hepatocytes as a platform for disease modeling and drug discovery. Front Med (Lausanne). 6(265)2019.PubMed/NCBI View Article : Google Scholar

14 

Takayama K and Mizuguchi H: Generation of human pluripotent stem cell-derived hepatocyte-like cells for drug toxicity screening. Drug Metab Pharmacokinet. 32:12–20. 2017.PubMed/NCBI View Article : Google Scholar

15 

Gao X, Yourick JJ and Sprando RL: Generation of nine induced pluripotent stem cell lines as an ethnic diversity panel. Stem Cell Res. 31:193–196. 2018.PubMed/NCBI View Article : Google Scholar

16 

Jung J, Zheng M, Goldfarb M and Zaret KS: Initiation of mammalian liver development from endoderm by fibroblast growth factors. Science. 284:1998–2003. 1999.PubMed/NCBI View Article : Google Scholar

17 

Basma H, Soto-Gutiérrez A, Yannam GR, Liu L, Ito R, Yamamoto T, Ellis E, Carson SD, Sato S, Chen Y, et al: Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology. 136:990–999. 2009.PubMed/NCBI View Article : Google Scholar

18 

Schneider CA, Rasband WS and Eliceiri KW: NIH image to imageJ: 25 Years of image analysis. Nat Methods. 9:671–675. 2012.PubMed/NCBI View Article : Google Scholar

19 

Asplund A, Pradip A, van Giezen M, Aspegren A, Choukair H, Rehnström M, Jacobsson S, Ghosheh N, El Hajjam D, Holmgren S, et al: One standardized differentiation procedure robustly generates homogenous hepatocyte cultures displaying metabolic diversity from a large panel of human pluripotent stem cells. Stem Cell Rev Rep. 12:90–104. 2016.PubMed/NCBI View Article : Google Scholar

20 

Gao X, Li R, Sprando RL and Yourick JJ: Concentration-dependent toxicogenomic changes of silver nanoparticles in hepatocyte-like cells derived from human induced pluripotent stem cells. Cell Biol Toxicol. 37:245–259. 2021.PubMed/NCBI View Article : Google Scholar

21 

Gao X, Li R, Cahan P, Zhao Y, Yourick JJ and Sprando RL: Hepatocyte-like cells derived from human induced pluripotent stem cells using small molecules: Implications of a transcriptomic study. Stem Cell Res Ther. 11(393)2020.PubMed/NCBI View Article : Google Scholar

22 

Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U and Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 4:249–264. 2003.PubMed/NCBI View Article : Google Scholar

23 

Fang H, Harris SC, Su Z, Chen M, Qian F, Shi L, Perkins R and Tong W: ArrayTrack: An FDA and public genomic tool. Methods Mol Biol. 1613:333–353. 2017.PubMed/NCBI View Article : Google Scholar

24 

Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, Lane HC and Lempicki RA: DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol. 4(P3)2003.PubMed/NCBI

25 

Huang DW, Sherman BT, Tan Q, Kir J, Liu D, Bryant D, Guo Y, Stephens R, Baseler MW, Lane HC and Lempicki RA: DAVID bioinformatics resources: Expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Res. 35 (Web Server Issue):W169–W175. 2007.PubMed/NCBI View Article : Google Scholar

26 

Chen G, Gulbranson DR, Hou Z, Bolin JM, Ruotti V, Probasco MD, Smuga-Otto K, Howden SE, Diol NR, Propson NE, et al: Chemically defined conditions for human iPSC derivation and culture. Nat Methods. 8:424–429. 2011.PubMed/NCBI View Article : Google Scholar

27 

Esteves F, Rueff J and Kranendonk M: The central role of cytochrome p450 in xenobiotic metabolism-a brief review on a fascinating enzyme family. J Xenobiot. 11:94–114. 2021.PubMed/NCBI View Article : Google Scholar

28 

Guengerich FP: Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol. 14:611–650. 2001.PubMed/NCBI View Article : Google Scholar

29 

Hayashi Y, Ohnuma K and Furue MK: Pluripotent stem cell heterogeneity. Adv Exp Med Biol. 1123:71–94. 2019.PubMed/NCBI View Article : Google Scholar

30 

Weinberger L, Ayyash M, Novershtern N and Hanna JH: Dynamic stem cell states: Naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol. 17:155–169. 2016.PubMed/NCBI View Article : Google Scholar

31 

Chen KG, Mallon BS, Hamilton RS, Kozhich OA, Park K, Hoeppner DJ, Robey PG and McKay RD: Non-colony type monolayer culture of human embryonic stem cells. Stem Cell Res. 9:237–248. 2012.PubMed/NCBI View Article : Google Scholar

32 

Kunova M, Matulka K, Eiselleova L, Salykin A, Kubikova I, Kyrylenko S, Hampl A and Dvorak P: Adaptation to robust monolayer expansion produces human pluripotent stem cells with improved viability. Stem Cells Transl Med. 2:246–254. 2013.PubMed/NCBI View Article : Google Scholar

33 

Bogacheva MS, Khan S, Kanninen LK, Yliperttula M, Leung AW and Lou YR: Differences in definitive endoderm induction approaches using growth factors and small molecules. J Cell Physiol. 233:3578–3589. 2018.PubMed/NCBI View Article : Google Scholar

34 

McLean AB, D'Amour KA, Jones KL, Krishnamoorthy M, Kulik MJ, Reynolds DM, Sheppard AM, Liu H, Xu Y, Baetge EE and Dalton S: Activin a efficiently specifies definitive endoderm from human embryonic stem cells only when phosphatidylinositol 3-kinase signaling is suppressed. Stem Cells. 25:29–38. 2007.PubMed/NCBI View Article : Google Scholar

35 

Ruijtenberg S and van den Heuvel S: Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression. Cell Cycle. 15:196–212. 2016.PubMed/NCBI View Article : Google Scholar

36 

Duan Y, Ma X, Zou W, Wang C, Bahbahan IS, Ahuja TP, Tolstikov V and Zern MA: Differentiation and characterization of metabolically functioning hepatocytes from human embryonic stem cells. Stem Cells. 28:674–686. 2010.PubMed/NCBI View Article : Google Scholar

37 

Baxter MA, Rowe C, Alder J, Harrison S, Hanley KP, Park BK, Kitteringham NR, Goldring CE and Hanley NA: Generating hepatic cell lineages from pluripotent stem cells for drug toxicity screening. Stem Cell Res. 5:4–22. 2010.PubMed/NCBI View Article : Google Scholar

38 

Rogler LE: Selective bipotential differentiation of mouse embryonic hepatoblasts in vitro. Am J Pathol. 150:591–602. 1997.PubMed/NCBI

39 

Czysz K, Minger S and Thomas N: DMSO efficiently down regulates pluripotency genes in human embryonic stem cells during definitive endoderm derivation and increases the proficiency of hepatic differentiation. PLoS One. 10(e0117689)2015.PubMed/NCBI View Article : Google Scholar

40 

Hay DC, Zhao D, Fletcher J, Hewitt ZA, McLean D, Urruticoechea-Uriguen A, Black JR, Elcombe C, Ross JA, Wolf R and Cui W: Efficient differentiation of hepatocytes from human embryonic stem cells exhibiting markers recapitulating liver development in vivo. Stem Cells. 26:894–902. 2008.PubMed/NCBI View Article : Google Scholar

41 

Michalopoulos GK: Principles of liver regeneration and growth homeostasis. Compr Physiol. 3:485–513. 2013.PubMed/NCBI View Article : Google Scholar

42 

Matsui T, Kinoshita T, Morikawa Y, Tohya K, Katsuki M, Ito Y, Kamiya A and Miyajima A: K-Ras mediates cytokine-induced formation of E-cadherin-based adherens junctions during liver development. EMBO J. 21:1021–1030. 2002.PubMed/NCBI View Article : Google Scholar

43 

Ren P, de Feijter AW, Paul DL and Ruch RJ: Enhancement of liver cell gap junction protein expression by glucocorticoids. Carcinogenesis. 15:1807–1813. 1994.PubMed/NCBI View Article : Google Scholar

44 

Fraczek J, Bolleyn J, Vanhaecke T, Rogiers V and Vinken M: Primary hepatocyte cultures for pharmaco-toxicological studies: At the busy crossroad of various anti-dedifferentiation strategies. Arch Toxicol. 87:577–610. 2013.PubMed/NCBI View Article : Google Scholar

45 

Schuetz EG, Schmid W, Schutz G, Brimer C, Yasuda K, Kamataki T, Bornheim L, Myles K and Cole TJ: The glucocorticoid receptor is essential for induction of cytochrome P-4502B by steroids but not for drug or steroid induction of CYP3A or P-450 reductase in mouse liver. Drug Metab Dispos. 28:268–278. 2000.PubMed/NCBI

46 

Chen C, Soto-Gutierrez A, Baptista PM and Spee B: Biotechnology challenges to in vitro maturation of hepatic stem cells. Gastroenterology. 154:1258–1272. 2018.PubMed/NCBI View Article : Google Scholar

47 

McCune JS, Hawke RL, LeCluyse EL, Gillenwater HH, Hamilton G, Ritchie J and Lindley C: In vivo and in vitro induction of human cytochrome P4503A4 by dexamethasone. Clin Pharmacol Ther. 68:356–366. 2000.PubMed/NCBI View Article : Google Scholar

48 

Benoist CC, Kawas LH, Zhu M, Tyson KA, Stillmaker L, Appleyard SM, Wright JW, Wayman GA and Harding JW: The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system. J Pharmacol Exp Ther. 351:390–402. 2014.PubMed/NCBI View Article : Google Scholar

49 

Kamiya A, Kinoshita T, Ito Y, Matsui T, Morikawa Y, Senba E, Nakashima K, Taga T, Yoshida K, Kishimoto T and Miyajima A: Fetal liver development requires a paracrine action of oncostatin M through the gp130 signal transducer. EMBO J. 18:2127–2136. 1999.PubMed/NCBI View Article : Google Scholar

50 

Kamiya A, Kinoshita T and Miyajima A: Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways. FEBS Lett. 492:90–94. 2001.PubMed/NCBI View Article : Google Scholar

51 

Mashek DG: Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD. Mol Metab. 50(101115)2021.PubMed/NCBI View Article : Google Scholar

52 

Gordillo M, Evans T and Gouon-Evans V: Orchestrating liver development. Development. 142:2094–2108. 2015.PubMed/NCBI View Article : Google Scholar

53 

Nguyen P, Leray V, Diez M, Serisier S, Le Bloc'h J, Siliart B and Dumon H: Liver lipid metabolism. J Anim Physiol Anim Nutr (Berl). 92:272–283. 2008.PubMed/NCBI View Article : Google Scholar

54 

Mathapati S, Siller R, Impellizzeri AA, Lycke M, Vegheim K, Almaas R and Sullivan GJ: Small-Molecule-Directed Hepatocyte-Like Cell Differentiation of Human Pluripotent stem cells. Curr Protoc Stem Cell Biol. 38:1G.6.1–1G.6.18. 2016.PubMed/NCBI View Article : Google Scholar

55 

Kiamehr M, Alexanova A, Viiri LE, Heiskanen L, Vihervaara T, Kauhanen D, Ekroos K, Laaksonen R, Käkelä R and Aalto-Setälä K: hiPSC-derived hepatocytes closely mimic the lipid profile of primary hepatocytes: A future personalised cell model for studying the lipid metabolism of the liver. J Cell Physiol. 234:3744–3761. 2019.PubMed/NCBI View Article : Google Scholar

56 

Zheng S, Yang Y, Wen C, Liu W, Cao L, Feng X, Chen J, Wang H, Tang Y, Tian L, et al: Effects of environmental contaminants in water resources on nonalcoholic fatty liver disease. Environ Int. 154(106555)2021.PubMed/NCBI View Article : Google Scholar

57 

Godoy P, Schmidt-Heck W, Natarajan K, Lucendo-Villarin B, Szkolnicka D, Asplund A, Björquist P, Widera A, Stöber R, Campos G, et al: Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells. J Hepatol. 63:934–942. 2015.PubMed/NCBI View Article : Google Scholar

58 

Faulkner-Jones A, Fyfe C, Cornelissen DJ, Gardner J, King J, Courtney A and Shu W: Bioprinting of human pluripotent stem cells and their directed differentiation into hepatocyte-like cells for the generation of mini-livers in 3D. Biofabrication. 7(044102)2015.PubMed/NCBI View Article : Google Scholar

59 

Beckwitt CH, Clark AM, Wheeler S, Taylor DL, Stolz DB, Griffith L and Wells A: Liver ‘organ on a chip’. Exp Cell Res. 363:15–25. 2018.PubMed/NCBI View Article : Google Scholar

60 

Xie Y, Yao J, Jin W, Ren L and Li X: Induction and maturation of hepatocyte-like cells in vitro: Focus on technological advances and challenges. Front Cell Dev Biol. 9(765980)2021.PubMed/NCBI View Article : Google Scholar

61 

Walker C, Mojares E and Del Río Hernández A: Role of extracellular matrix in development and cancer progression. Int J Mol Sci. 19(3028)2018.PubMed/NCBI View Article : Google Scholar

62 

Okita K and Yamanaka S: Intracellular signaling pathways regulating pluripotency of embryonic stem cells. Curr Stem Cell Res Ther. 1:103–111. 2006.PubMed/NCBI View Article : Google Scholar

63 

Itoh F, Watabe T and Miyazono K: Roles of TGF-β family signals in the fate determination of pluripotent stem cells. Semin Cell Dev Biol. 32:98–106. 2014.PubMed/NCBI View Article : Google Scholar

64 

Bielen H and Houart C: The Wnt cries many: Wnt regulation of neurogenesis through tissue patterning, proliferation, and asymmetric cell division. Dev Neurobiol. 74:772–780. 2014.PubMed/NCBI View Article : Google Scholar

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Li R, Zhao Y, Yourick JJ, Sprando RL and Gao X: Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells. Biomed Rep 16: 43, 2022.
APA
Li, R., Zhao, Y., Yourick, J.J., Sprando, R.L., & Gao, X. (2022). Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells. Biomedical Reports, 16, 43. https://doi.org/10.3892/br.2022.1526
MLA
Li, R., Zhao, Y., Yourick, J. J., Sprando, R. L., Gao, X."Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells". Biomedical Reports 16.5 (2022): 43.
Chicago
Li, R., Zhao, Y., Yourick, J. J., Sprando, R. L., Gao, X."Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells". Biomedical Reports 16, no. 5 (2022): 43. https://doi.org/10.3892/br.2022.1526
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Spandidos Publications style
Li R, Zhao Y, Yourick JJ, Sprando RL and Gao X: Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells. Biomed Rep 16: 43, 2022.
APA
Li, R., Zhao, Y., Yourick, J.J., Sprando, R.L., & Gao, X. (2022). Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells. Biomedical Reports, 16, 43. https://doi.org/10.3892/br.2022.1526
MLA
Li, R., Zhao, Y., Yourick, J. J., Sprando, R. L., Gao, X."Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells". Biomedical Reports 16.5 (2022): 43.
Chicago
Li, R., Zhao, Y., Yourick, J. J., Sprando, R. L., Gao, X."Phenotypical, functional and transcriptomic comparison of two modified methods of hepatocyte differentiation from human induced pluripotent stem cells". Biomedical Reports 16, no. 5 (2022): 43. https://doi.org/10.3892/br.2022.1526
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