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Human Pluripotent Stem Cell-Derived Hepatocytes Show Higher Transcriptional Correlation with Adult Liver Tissue than with Fetal Liver Tissue
Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. (Translationell bioinformatik, Translational Bioinformatics)ORCID-id: 0000-0003-2942-6702
Takara Bio Europe AB, Gothenburg, Sweden.
Takara Bio Europe AB, Gothenburg, Sweden.
Takara Bio Europe AB, Gothenburg, Sweden.
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2020 (Engelska)Ingår i: ACS Omega, ISSN 2470-1343, Vol. 5, nr 10, s. 4816-4827Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Human pluripotent stem cell-derived hepatocytes (hPSC-HEP) display many properties of mature hepatocytes, including expression of important genes of the drug metabolizing machinery, glycogen storage, and production of multiple serum proteins. To this date, hPSC-HEP do not, however, fully recapitulate the complete functionality of in vivo mature hepatocytes. In this study, we applied versatile bioinformatic algorithms, including functional annotation and pathway enrichment analyses, transcription factor binding-site enrichment, and similarity and correlation analyses, to datasets collected from different stages during hPSC-HEP differentiation and compared these to developmental stages and tissues from fetal and adult human liver. Our results demonstrate a high level of similarity between the in vitro differentiation of hPSC-HEP and in vivo hepatogenesis. Importantly, the transcriptional correlation of hPSC-HEP with adult liver (AL) tissues was higher than with fetal liver (FL) tissues (0.83 and 0.70, respectively). Functional data revealed mature features of hPSC-HEP including cytochrome P450 enzymes activities and albumin secretion. Moreover, hPSC-HEP showed expression of many genes involved in drug absorption, distribution, metabolism, and excretion. Despite the high similarities observed, we identified differences of specific pathways and regulatory players by analyzing the gene expression between hPSC-HEP and AL. These findings will aid future intervention and improvement of in vitro hepatocyte differentiation protocol in order to generate hepatocytes displaying the complete functionality of mature hepatocytes. Finally, on the transcriptional level, our results show stronger correlation and higher similarity of hPSC-HEP to AL than to FL. In addition, potential targets for further functional improvement of hPSC-HEP were also identified. 

Ort, förlag, år, upplaga, sidor
American Chemical Society (ACS), 2020. Vol. 5, nr 10, s. 4816-4827
Nationell ämneskategori
Cell- och molekylärbiologi Gastroenterologi Bioinformatik och systembiologi
Forskningsämne
Bioinformatik
Identifikatorer
URN: urn:nbn:se:his:diva-18337DOI: 10.1021/acsomega.9b03514ISI: 000520853400013PubMedID: 32201767Scopus ID: 2-s2.0-85081208923OAI: oai:DiVA.org:his-18337DiVA, id: diva2:1416033
Tillgänglig från: 2020-03-20 Skapad: 2020-03-20 Senast uppdaterad: 2020-04-22Bibliografiskt granskad

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Ghosheh, NidalSartipy, PeterSynnergren, Jane

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