Direct conversion of porcine primary fibroblasts into hepatocyte-like cells.
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Fráguas-Eggenschwiler et al.pdf
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Authors
Fráguas-Eggenschwiler, MarianeEggenschwiler, Reto
Söllner, Jenny-Helena
Cortnumme, Leon
Vondran, Florian W R
Cantz, Tobias
Ott, Michael
Niemann, Heiner
Issue Date
2021-04-29
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Show full item recordAbstract
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.Citation
Sci Rep. 2021 Apr 29;11(1):9334. doi: 10.1038/s41598-021-88727-1.Affiliation
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.Publisher
Nature ResearchJournal
Scientific reportsPubMed ID
33927320Type
ArticleLanguage
enEISSN
2045-2322ae974a485f413a2113503eed53cd6c53
10.1038/s41598-021-88727-1
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