Comparing in vitro human liver models to in vivo human liver using RNA-Seq

  1. Gupta, Rajinder ORCID logo
  2. Schrooders, Yannick
  3. Hauser, Duncan
  4. van Herwijnen, Marcel
  5. Albrecht, Wiebke ORCID logo
  6. ter Braak, Bas
  7. Brecklinghaus, Tim ORCID logo
  8. Castell, Jose V.
  9. Elenschneider, Leroy
  10. Escher, Sylvia
  11. Guye, Patrick
  12. Hengstler, Jan ORCID logo
  13. Ghallab, Ahmed ORCID logo
  14. Hansen, Tanja
  15. Leist, Marcel
  16. Maclennan, Richard
  17. Moritz, Wolfgang
  18. Tolosa, Laia
  19. Tricot, Tine
  20. Verfaillie, Catherine
  21. Walker, Paul
  22. van de Water, Bob
  23. Kleinjans, Jos
  24. Caiment, Florian

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Gupta2021_Article_ComparingInVitroHumanLiverMode.pdf 6,79MB
WeightNameValue
1000 Titel
  • Comparing in vitro human liver models to in vivo human liver using RNA-Seq
1000 Autor/in
  1. Gupta, Rajinder |
  2. Schrooders, Yannick |
  3. Hauser, Duncan |
  4. van Herwijnen, Marcel |
  5. Albrecht, Wiebke |
  6. ter Braak, Bas |
  7. Brecklinghaus, Tim |
  8. Castell, Jose V. |
  9. Elenschneider, Leroy |
  10. Escher, Sylvia |
  11. Guye, Patrick |
  12. Hengstler, Jan |
  13. Ghallab, Ahmed |
  14. Hansen, Tanja |
  15. Leist, Marcel |
  16. Maclennan, Richard |
  17. Moritz, Wolfgang |
  18. Tolosa, Laia |
  19. Tricot, Tine |
  20. Verfaillie, Catherine |
  21. Walker, Paul |
  22. van de Water, Bob |
  23. Kleinjans, Jos |
  24. Caiment, Florian |
1000 Erscheinungsjahr 2020
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-10-27
1000 Erschienen in
1000 Quellenangabe
  • 95:573-589
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00204-020-02937-6 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870774 |
1000 Ergänzendes Material
  • https://link.springer.com/article/10.1007/s00204-020-02937-6#Sec15 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different in vitro cell models have been developed in the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze the following human in vitro liver cell models in comparison to human liver tissue: cancer-derived cell lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous human liver-derived assays (hPCLiS, human precision cut liver slices), non-cancerous human liver-derived assays (PHH, primary human hepatocytes) and 3D liver microtissues. First, using CellNet, we analyzed whether these liver in vitro cell models were indeed classified as liver, based on their baseline expression profile and gene regulatory networks (GRN). More comprehensive analyses using non-differentially expressed genes (non-DEGs) and differential transcript usage (DTU) were applied to assess the coverage for important liver pathways. Through different analyses, we noticed that 3D liver microtissues exhibited a high similarity with in vivo liver, in terms of CellNet (C/T score: 0.98), non-DEGs (10,363) and pathway coverage (highest for 19 out of 20 liver specific pathways shown) at the beginning of the incubation period (0 h) followed by a decrease during long-term incubation for 168 and 336 h. PHH also showed a high degree of similarity with human liver tissue and allowed stable conditions for a short-term cultivation period of 24 h. Using the same metrics, HepG2 cells illustrated the lowest similarity (C/T: 0.51, non-DEGs: 5623, and pathways coverage: least for 7 out of 20) with human liver tissue. The HepG2 are widely used in hepatotoxicity studies, however, due to their lower similarity, they should be used with caution. HepaRG models, iPSC-HLCs, and hPCLiS ranged clearly behind microtissues and PHH but showed higher similarity to human liver tissue than HepG2 cells. In conclusion, this study offers a resource of RNA-Seq data of several biological replicates of human liver cell models in vitro compared to human liver tissue.
1000 Sacherschließung
lokal RNA-seq
lokal Non-DEGs DTU-
lokal In vivo liver
lokal Non-DEGs
lokal In vitro liver
lokal Pathway coverage
lokal CellNet
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-3342-2122|https://frl.publisso.de/adhoc/uri/U2Nocm9vZGVycywgWWFubmljaw==|https://frl.publisso.de/adhoc/uri/SGF1c2VyLCBEdW5jYW4=|https://frl.publisso.de/adhoc/uri/dmFuIEhlcndpam5lbiwgTWFyY2Vs|https://orcid.org/0000-0002-0800-4933|https://frl.publisso.de/adhoc/uri/dGVyIEJyYWFrLCBCYXM=|https://orcid.org/0000-0001-6650-9166|https://frl.publisso.de/adhoc/uri/Q2FzdGVsbCwgSm9zZSBWLg==|https://frl.publisso.de/adhoc/uri/RWxlbnNjaG5laWRlciwgTGVyb3k=|https://frl.publisso.de/adhoc/uri/RXNjaGVyLCBTeWx2aWE=|https://frl.publisso.de/adhoc/uri/R3V5ZSwgUGF0cmljaw==|https://orcid.org/0000-0002-1427-5246|https://orcid.org/0000-0003-0695-3403|https://frl.publisso.de/adhoc/uri/SGFuc2VuLCBUYW5qYQ==|https://frl.publisso.de/adhoc/uri/TGVpc3QsIE1hcmNlbA==|https://frl.publisso.de/adhoc/uri/TWFjbGVubmFuLCBSaWNoYXJk|https://frl.publisso.de/adhoc/uri/TW9yaXR6LCBXb2xmZ2FuZw==|https://frl.publisso.de/adhoc/uri/VG9sb3NhLCBMYWlh|https://frl.publisso.de/adhoc/uri/VHJpY290LCBUaW5l|https://frl.publisso.de/adhoc/uri/VmVyZmFpbGxpZSwgQ2F0aGVyaW5l|https://frl.publisso.de/adhoc/uri/V2Fsa2VyLCBQYXVs|https://frl.publisso.de/adhoc/uri/dmFuIGRlIFdhdGVyLCBCb2I=|https://frl.publisso.de/adhoc/uri/S2xlaW5qYW5zLCBKb3M=|https://frl.publisso.de/adhoc/uri/Q2FpbWVudCwgRmxvcmlhbg==
1000 Label
1000 Förderer
  1. Horizon 2020 Framework Programme |
  2. Instituto de Salud Carlos III |
  3. European Regional Development Fund |
  4. Federación Española de Enfermedades Raras |
1000 Fördernummer
  1. 681002
  2. -
  3. CP16/00097
  4. CP16/00097
1000 Förderprogramm
  1. EU-ToxRisk
  2. Plan Estatal de I + D + i 2013–2016
  3. A way to achieve Europe
  4. A way to achieve Europe
1000 Dateien
  1. Comparing in vitro human liver models to in vivo human liver using RNA-Seq
    Comparing in vitro human liver models to in vivo human liver using RNA-Seq
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Horizon 2020 Framework Programme |
    1000 Förderprogramm EU-ToxRisk
    1000 Fördernummer 681002
  2. 1000 joinedFunding-child
    1000 Förderer Instituto de Salud Carlos III |
    1000 Förderprogramm Plan Estatal de I + D + i 2013–2016
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer European Regional Development Fund |
    1000 Förderprogramm A way to achieve Europe
    1000 Fördernummer CP16/00097
  4. 1000 joinedFunding-child
    1000 Förderer Federación Española de Enfermedades Raras |
    1000 Förderprogramm A way to achieve Europe
    1000 Fördernummer CP16/00097
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6428835.rdf
1000 Erstellt am 2021-08-11T12:18:55.279+0200
1000 Erstellt von 254
1000 beschreibt frl:6428835
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet 2021-10-13T08:33:15.189+0200
1000 Objekt bearb. Wed Oct 13 08:18:52 CEST 2021
1000 Vgl. frl:6428835
1000 Oai Id
  1. oai:frl.publisso.de:frl:6428835 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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