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FältnamnIndikatorerMetadata
00007802naa a2200601 4500
001oai:DiVA.org:his-11775
003SwePub
008151221s2015 | |||||||||||000 ||eng|
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-117752 URI
0247 a https://doi.org/10.1016/j.jhep.2015.05.0132 DOI
040 a (SwePub)his
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Godoy, Patriciou IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany / Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chile4 aut
2451 0a Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells
264 1b Elsevier,c 2015
338 a electronic2 rdacarrier
500 a CC BY 4.0Corrigendum in: Journal of Hepatology, Volume 64, February 2016, Pages 525-526. doi:10.1016/j.jhep.2015.11.003This study was supported by the European Union Seventh Framework Programme (FP7)-Health projects DETECTIVE (EU-project FP7-Health Grant Agreement No. 266838) and NOTOX (EU-project FP7-Health Grant Agreement No. 267038), and the BMBF (German Federal Ministry of Education and Research) project Virtual Liver (0313854). Dr David C. Hay was supported by the UK Regenerative medicine platform (MR/K026666/1 and MR/L022974/1). Mr. Baltasar Lucendo-Villarin and Ms. Dagmara Szkolnicka were funded by MRC PhD studentships.
520 a BACKGROUND & AIMS: The differentiation of stem cells to hepatocyte-like cells (HLC) offers the perspective of unlimited supply of human hepatocytes. However, the degree of differentiation of HLC remains controversial. To obtain an unbiased characterization, we performed a transcriptomic study with HLC derived from human embryonic and induced stem cells (ESC, hiPSC) from three different laboratories.METHODS: Genome-wide gene expression profiles of ESC and HLC were compared to freshly isolated and up to 14days cultivated primary human hepatocytes. Gene networks representing successful and failed hepatocyte differentiation, and the transcription factors involved in their regulation were identified.RESULTS: Gene regulatory network analysis demonstrated that HLC represent a mixed cell type with features of liver, intestine, fibroblast and stem cells. The "unwanted" intestinal features were associated with KLF5 and CDX2 transcriptional networks. Cluster analysis identified highly correlated groups of genes associated with mature liver functions (n=1057) and downregulated proliferation associated genes (n=1562) that approach levels of primary hepatocytes. However, three further clusters containing 447, 101, and 505 genes failed to reach levels of hepatocytes. Key TF of two of these clusters include SOX11, FOXQ1, and YBX3. The third unsuccessful cluster, controlled by HNF1, CAR, FXR, and PXR, strongly overlaps with genes repressed in cultivated hepatocytes compared to freshly isolated hepatocytes, suggesting that current in vitro conditions lack stimuli required to maintain gene expression in hepatocytes, which consequently also explains a corresponding deficiency of HLC.CONCLUSIONS: The present gene regulatory network approach identifies key transcription factors which require modulation to improve HLC differentiation.
650 7a NATURVETENSKAPx Biologix Cellbiologi0 (SwePub)106042 hsv//swe
650 7a NATURAL SCIENCESx Biological Sciencesx Cell Biology0 (SwePub)106042 hsv//eng
653 a Bioinformatik
653 a Bioinformatics
7001 a Schmidt-Heck, Wolfgangu Leibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knöll Institute, Jena, Germany4 aut
7001 a Natarajan, Karthicku University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany4 aut
7001 a Lucendo-Villarin, Baltasaru MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom4 aut
7001 a Szkolnicka, Dagmarau MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom4 aut
7001 a Asplund, Annikau Högskolan i Skövde,Institutionen för biovetenskap,Forskningscentrum för Systembiologi,Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden,Bioinformatik, Bioinformatics4 aut0 (Swepub:his)aspa
7001 a Björquist, Petteru NovaHep AB, Gothenburg, Sweden4 aut
7001 a Widera, Agatau IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany4 aut
7001 a Stöber, Reginau IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany4 aut
7001 a Campos, Giselau IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany4 aut
7001 a Hammad, Seddiku IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany4 aut
7001 a Sachinidis, Agapiosu University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany4 aut
7001 a Chaudhari, Umeshu University of Cologne, Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), Cologne, Germany4 aut
7001 a Damm, Georgu Charité University Medicine Berlin, Department of General-, Visceral- and Transplantation Surgery, Berlin, Germany4 aut
7001 a Weiss, Thomas S.u Center for Liver Cell Research, Department of Pediatrics and Juvenile Medicine, University of Regensburg Hospital, Regensburg, Germany4 aut
7001 a Nüssler, Andreasu Eberhard Karls University Tübingen, BG Trauma Center, Siegfried Weller Institut, Tübingen, Germany4 aut
7001 a Synnergren, Janeu Högskolan i Skövde,Institutionen för biovetenskap,Forskningscentrum för Systembiologi,Bioinformatics4 aut0 (Swepub:his)synj
7001 a Edlund, Karolinau IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany4 aut
7001 a Küppers-Munther, Barbarau Takara Bio Europe AB (former Cellartis AB), Gothenburg, Sweden4 aut
7001 a Hay, David C.u MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, United Kingdom4 aut
7001 a Hengstler, Jan G.u IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany4 aut
7102 a IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany / Department of Physiology, Faculty of Biological Sciences, University of Concepción, Chileb Leibniz Institute for Natural Product Research and Infection Biology eV-Hans-Knöll Institute, Jena, Germany4 org
7730 t Journal of Hepatologyd : Elsevierg 63:4, s. 934-942q 63:4<934-942x 0168-8278x 1600-0641
8564 u https://doi.org/10.1016/j.jhep.2015.05.013y Fulltext
8564 u https://doi.org/10.1016/j.jhep.2015.11.003y Corrigendum to “Gene networks and transcription factor motifs defining the differentiation of human stem cells into hepatocyte-like cells” [J Hepatol 2015;63:934–942]
8564 u https://his.diva-portal.org/smash/get/diva2:885782/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
8564 u http://www.journal-of-hepatology.eu/article/S0168827815003402/pdf
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-11775
8564 8u https://doi.org/10.1016/j.jhep.2015.05.013

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