Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro
Direct reprogramming of somatic cells into pluripotent cells by retrovirus-mediated expression of OCT4, SOX2, KLF4, and C-MYC is a promising approach to derive disease-specific induced pluripotent stem cells (iPSCs). In this study, we focused on three murine models for metabolic liver disorders: the...
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.4061/2011/924782 |
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| author | Reto Eggenschwiler Komal Loya Malte Sgodda Francoise André Tobias Cantz |
| author_facet | Reto Eggenschwiler Komal Loya Malte Sgodda Francoise André Tobias Cantz |
| author_sort | Reto Eggenschwiler |
| collection | DOAJ |
| description | Direct reprogramming of somatic cells into pluripotent cells by retrovirus-mediated expression of OCT4, SOX2, KLF4, and C-MYC is a promising approach to derive disease-specific induced pluripotent stem cells (iPSCs). In this study, we focused on three murine models for metabolic liver disorders: the copper storage disorder Wilson's disease (toxic-milk mice), tyrosinemia type 1 (fumarylacetoacetate-hydrolase deficiency, FAH−/− mice), and alpha1-antitrypsin deficiency (PiZ mice). Colonies of iPSCs emerged 2-3 weeks after transduction of fibroblasts, prepared from each mouse strain, and were maintained as individual iPSC lines. RT-PCR and immunofluorescence analyses demonstrated the expression of endogenous pluripotency markers. Hepatic precursor cells could be derived from these disease-specific iPSCs applying an in vitro differentiation protocol and could be visualized after transduction of a lentiviral albumin-GFP reporter construct. Functional characterization of these cells allowed the recapitulation of the disease phenotype for further studies of underlying molecular mechanisms of the respective disease. |
| format | Article |
| id | doaj-art-5e95e760fac44d0aa9e4deb597890f05 |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-5e95e760fac44d0aa9e4deb597890f052025-02-03T01:26:00ZengWileyStem Cells International1687-966X1687-96782011-01-01201110.4061/2011/924782924782Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In VitroReto Eggenschwiler0Komal Loya1Malte Sgodda2Francoise André3Tobias Cantz4Stem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, GermanyStem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, GermanyStem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, GermanyStem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, GermanyStem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, GermanyDirect reprogramming of somatic cells into pluripotent cells by retrovirus-mediated expression of OCT4, SOX2, KLF4, and C-MYC is a promising approach to derive disease-specific induced pluripotent stem cells (iPSCs). In this study, we focused on three murine models for metabolic liver disorders: the copper storage disorder Wilson's disease (toxic-milk mice), tyrosinemia type 1 (fumarylacetoacetate-hydrolase deficiency, FAH−/− mice), and alpha1-antitrypsin deficiency (PiZ mice). Colonies of iPSCs emerged 2-3 weeks after transduction of fibroblasts, prepared from each mouse strain, and were maintained as individual iPSC lines. RT-PCR and immunofluorescence analyses demonstrated the expression of endogenous pluripotency markers. Hepatic precursor cells could be derived from these disease-specific iPSCs applying an in vitro differentiation protocol and could be visualized after transduction of a lentiviral albumin-GFP reporter construct. Functional characterization of these cells allowed the recapitulation of the disease phenotype for further studies of underlying molecular mechanisms of the respective disease.http://dx.doi.org/10.4061/2011/924782 |
| spellingShingle | Reto Eggenschwiler Komal Loya Malte Sgodda Francoise André Tobias Cantz Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro Stem Cells International |
| title | Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro |
| title_full | Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro |
| title_fullStr | Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro |
| title_full_unstemmed | Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro |
| title_short | Hepatic Differentiation of Murine Disease-Specific Induced Pluripotent Stem Cells Allows Disease Modelling In Vitro |
| title_sort | hepatic differentiation of murine disease specific induced pluripotent stem cells allows disease modelling in vitro |
| url | http://dx.doi.org/10.4061/2011/924782 |
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