Direct conversion of porcine primary fibroblasts into hepatocyte-like cells

Abstract The pig is an important model organism for biomedical research, mainly due to its extensive genetic, physiological and anatomical similarities with humans. Until date, direct conversion of somatic cells into hepatocyte-like cells (iHeps) has only been achieved in rodents and human cells. He...

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Autores principales:	Mariane Fráguas-Eggenschwiler, Reto Eggenschwiler, Jenny-Helena Söllner, Leon Cortnumme, Florian W. R. Vondran, Tobias Cantz, Michael Ott, Heiner Niemann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ebf1a2a015ce40df82ada5612eabbae4
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spelling	oai:doaj.org-article:ebf1a2a015ce40df82ada5612eabbae42021-12-02T13:41:44ZDirect conversion of porcine primary fibroblasts into hepatocyte-like cells10.1038/s41598-021-88727-12045-2322https://doaj.org/article/ebf1a2a015ce40df82ada5612eabbae42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88727-1https://doaj.org/toc/2045-2322Abstract The pig is an important model organism for biomedical research, mainly due to its extensive genetic, physiological and anatomical similarities with humans. Until date, direct conversion of somatic cells into hepatocyte-like cells (iHeps) has only been achieved in rodents and human cells. Here, we employed lentiviral vectors to screen a panel of 12 hepatic transcription factors (TF) for their potential to convert porcine fibroblasts into hepatocyte-like cells. We demonstrate for the first time, hepatic conversion of porcine somatic cells by over-expression of CEBPα, FOXA1 and HNF4α2 (3TF-piHeps). Reprogrammed 3TF-piHeps display a hepatocyte-like morphology and show functional characteristics of hepatic cells, including albumin secretion, Dil-AcLDL uptake, storage of lipids and glycogen and activity of cytochrome P450 enzymes CYP1A2 and CYP2C33 (CYP2C9 in humans). Moreover, we show that markers of mature hepatocytes are highly expressed in 3TF-piHeps, while fibroblastic markers are reduced. We envision piHeps as useful cell sources for future studies on drug metabolism and toxicity as well as in vitro models for investigation of pig-to-human infectious diseases.Mariane Fráguas-EggenschwilerReto EggenschwilerJenny-Helena SöllnerLeon CortnummeFlorian W. R. VondranTobias CantzMichael OttHeiner NiemannNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mariane Fráguas-Eggenschwiler Reto Eggenschwiler Jenny-Helena Söllner Leon Cortnumme Florian W. R. Vondran Tobias Cantz Michael Ott Heiner Niemann Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
description	Abstract The pig is an important model organism for biomedical research, mainly due to its extensive genetic, physiological and anatomical similarities with humans. Until date, direct conversion of somatic cells into hepatocyte-like cells (iHeps) has only been achieved in rodents and human cells. Here, we employed lentiviral vectors to screen a panel of 12 hepatic transcription factors (TF) for their potential to convert porcine fibroblasts into hepatocyte-like cells. We demonstrate for the first time, hepatic conversion of porcine somatic cells by over-expression of CEBPα, FOXA1 and HNF4α2 (3TF-piHeps). Reprogrammed 3TF-piHeps display a hepatocyte-like morphology and show functional characteristics of hepatic cells, including albumin secretion, Dil-AcLDL uptake, storage of lipids and glycogen and activity of cytochrome P450 enzymes CYP1A2 and CYP2C33 (CYP2C9 in humans). Moreover, we show that markers of mature hepatocytes are highly expressed in 3TF-piHeps, while fibroblastic markers are reduced. We envision piHeps as useful cell sources for future studies on drug metabolism and toxicity as well as in vitro models for investigation of pig-to-human infectious diseases.
format	article
author	Mariane Fráguas-Eggenschwiler Reto Eggenschwiler Jenny-Helena Söllner Leon Cortnumme Florian W. R. Vondran Tobias Cantz Michael Ott Heiner Niemann
author_facet	Mariane Fráguas-Eggenschwiler Reto Eggenschwiler Jenny-Helena Söllner Leon Cortnumme Florian W. R. Vondran Tobias Cantz Michael Ott Heiner Niemann
author_sort	Mariane Fráguas-Eggenschwiler
title	Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title_short	Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title_full	Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title_fullStr	Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title_full_unstemmed	Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title_sort	direct conversion of porcine primary fibroblasts into hepatocyte-like cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ebf1a2a015ce40df82ada5612eabbae4
work_keys_str_mv	AT marianefraguaseggenschwiler directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT retoeggenschwiler directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT jennyhelenasollner directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT leoncortnumme directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT florianwrvondran directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT tobiascantz directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT michaelott directconversionofporcineprimaryfibroblastsintohepatocytelikecells AT heinerniemann directconversionofporcineprimaryfibroblastsintohepatocytelikecells
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Direct conversion of porcine primary fibroblasts into hepatocyte-like cells

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