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Direct conversion of porcine primary fibroblasts into hepatocyte-like cells

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 em...

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Autores principales: Fráguas-Eggenschwiler, Mariane, Eggenschwiler, Reto, Söllner, Jenny-Helena, Cortnumme, Leon, Vondran, Florian W. R., Cantz, Tobias, Ott, Michael, Niemann, Heiner
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085017/
https://www.ncbi.nlm.nih.gov/pubmed/33927320
http://dx.doi.org/10.1038/s41598-021-88727-1
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author Fráguas-Eggenschwiler, Mariane
Eggenschwiler, Reto
Söllner, Jenny-Helena
Cortnumme, Leon
Vondran, Florian W. R.
Cantz, Tobias
Ott, Michael
Niemann, Heiner
author_facet Fráguas-Eggenschwiler, Mariane
Eggenschwiler, Reto
Söllner, Jenny-Helena
Cortnumme, Leon
Vondran, Florian W. R.
Cantz, Tobias
Ott, Michael
Niemann, Heiner
author_sort Fráguas-Eggenschwiler, Mariane
collection PubMed
description 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.
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spelling pubmed-80850172021-05-03 Direct conversion of porcine primary fibroblasts into hepatocyte-like cells Fráguas-Eggenschwiler, Mariane Eggenschwiler, Reto Söllner, Jenny-Helena Cortnumme, Leon Vondran, Florian W. R. Cantz, Tobias Ott, Michael Niemann, Heiner Sci Rep Article 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. Nature Publishing Group UK 2021-04-29 /pmc/articles/PMC8085017/ /pubmed/33927320 http://dx.doi.org/10.1038/s41598-021-88727-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fráguas-Eggenschwiler, Mariane
Eggenschwiler, Reto
Söllner, Jenny-Helena
Cortnumme, Leon
Vondran, Florian W. R.
Cantz, Tobias
Ott, Michael
Niemann, Heiner
Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title 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_short Direct conversion of porcine primary fibroblasts into hepatocyte-like cells
title_sort direct conversion of porcine primary fibroblasts into hepatocyte-like cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085017/
https://www.ncbi.nlm.nih.gov/pubmed/33927320
http://dx.doi.org/10.1038/s41598-021-88727-1
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