Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks

Abstract Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis...

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Autores principales:	Peggy Matz, Wasco Wruck, Beatrix Fauler, Diran Herebian, Thorsten Mielke, James Adjaye
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c385b3a75a5f4e1aa1175941ad215751
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spelling	oai:doaj.org-article:c385b3a75a5f4e1aa1175941ad2157512021-12-02T15:05:20ZFootprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks10.1038/s41598-017-06546-92045-2322https://doaj.org/article/c385b3a75a5f4e1aa1175941ad2157512017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06546-9https://doaj.org/toc/2045-2322Abstract Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by electron microscopy revealed the presence of lipid and glycogen storage, tight junctions and bile canaliculi- all typical features of hepatocytes. Furthermore, the transcriptome of undifferentiated E-iPSC, DE, HE and HLCs were compared to that of fetal liver and primary human hepatocytes (PHH). K-means clustering identified 100 clusters which include developmental stage-specific groups of genes, e.g. OCT4 expression at the undifferentiated stage, SOX17 marking the DE stage, DLK and HNF6 the HE stage, HNF4α and Albumin is specific to HLCs, fetal liver and adult liver (PHH) stage. We use E-iPSCs for modeling gene regulatory networks associated with human hepatogenesis and gastrulation in general.Peggy MatzWasco WruckBeatrix FaulerDiran HerebianThorsten MielkeJames AdjayeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Peggy Matz Wasco Wruck Beatrix Fauler Diran Herebian Thorsten Mielke James Adjaye Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
description	Abstract Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells and can be generated from somatic cells. We have generated episomal plasmid-based and integration-free iPSCs (E-iPSCs) from human fetal foreskin fibroblast cells (HFF1). We used an E-iPSC-line to model hepatogenesis in vitro. The HLCs were characterized biochemically, i.e. glycogen storage, ICG uptake and release, UREA and bile acid production, as well as CYP3A4 activity. Ultra-structure analysis by electron microscopy revealed the presence of lipid and glycogen storage, tight junctions and bile canaliculi- all typical features of hepatocytes. Furthermore, the transcriptome of undifferentiated E-iPSC, DE, HE and HLCs were compared to that of fetal liver and primary human hepatocytes (PHH). K-means clustering identified 100 clusters which include developmental stage-specific groups of genes, e.g. OCT4 expression at the undifferentiated stage, SOX17 marking the DE stage, DLK and HNF6 the HE stage, HNF4α and Albumin is specific to HLCs, fetal liver and adult liver (PHH) stage. We use E-iPSCs for modeling gene regulatory networks associated with human hepatogenesis and gastrulation in general.
format	article
author	Peggy Matz Wasco Wruck Beatrix Fauler Diran Herebian Thorsten Mielke James Adjaye
author_facet	Peggy Matz Wasco Wruck Beatrix Fauler Diran Herebian Thorsten Mielke James Adjaye
author_sort	Peggy Matz
title	Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
title_short	Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
title_full	Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
title_fullStr	Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
title_full_unstemmed	Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks
title_sort	footprint-free human fetal foreskin derived ipscs: a tool for modeling hepatogenesis associated gene regulatory networks
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c385b3a75a5f4e1aa1175941ad215751
work_keys_str_mv	AT peggymatz footprintfreehumanfetalforeskinderivedipscsatoolformodelinghepatogenesisassociatedgeneregulatorynetworks AT wascowruck footprintfreehumanfetalforeskinderivedipscsatoolformodelinghepatogenesisassociatedgeneregulatorynetworks AT beatrixfauler footprintfreehumanfetalforeskinderivedipscsatoolformodelinghepatogenesisassociatedgeneregulatorynetworks AT diranherebian footprintfreehumanfetalforeskinderivedipscsatoolformodelinghepatogenesisassociatedgeneregulatorynetworks AT thorstenmielke footprintfreehumanfetalforeskinderivedipscsatoolformodelinghepatogenesisassociatedgeneregulatorynetworks AT jamesadjaye footprintfreehumanfetalforeskinderivedipscsatoolformodelinghepatogenesisassociatedgeneregulatorynetworks
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Footprint-free human fetal foreskin derived iPSCs: A tool for modeling hepatogenesis associated gene regulatory networks

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