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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents



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ID: 732095.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis
Authors:Song, G.; Pacher, M.; Balakrishnan, A.; Yuan, Q.; Tsay, H. C.; Yang, D.; Reetz, J.; Brandes, S.; Dai, Z.; Putzer, B. M.; Arauzo-Bravo, M. J.; Steinemann, D.; Luedde, T.; Schwabe, R. F.; Manns, M. P.; Scholer, H. R.; Schambach, A.; Cantz, T.; Ott, M.; Sharma, A. D.
Date of Publication (YYYY-MM-DD):2016-02-23
Title of Journal:Cell Stem Cell
Volume:18
Issue / Number:6
Start Page:797
End Page:808
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Direct induction of induced hepatocytes (iHeps) from fibroblasts holds potential as a strategy for regenerative medicine but until now has only been shown in culture settings. Here, we describe in vivo iHep formation using transcription factor induction and genetic fate tracing in mouse models of chronic liver disease. We show that ectopic expression of the transcription factors FOXA3, GATA4, HNF1A, and HNF4A from a polycistronic lentiviral vector converts mouse myofibroblasts into cells with a hepatocyte phenotype. In vivo expression of the same set of transcription factors from a p75 neurotrophin receptor peptide (p75NTRp)-tagged adenovirus enabled the generation of hepatocyte-like cells from myofibroblasts in fibrotic mouse livers and reduced liver fibrosis. We have therefore been able to convert pro-fibrogenic myofibroblasts in the liver into hepatocyte-like cells with positive functional benefits. This direct in vivo reprogramming approach may open new avenues for the treatment of chronic liver disease.
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany; Twincore Centre for Experimental and Clinical Infection Research, Hannover 30625, Germany. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany; Junior Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Hannover 30625, Germany; Twincore Centre for Experimental and Clinical Infection Research, Hannover 30625, Germany. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany; Junior Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Hannover 30625, Germany. Institute for Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock 18057, Germany. Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastian 20014, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao 48013, Spain. Institute of Human Genetics, Hannover Medical School, Hannover 30625, Germany. Division of Hepatobiliary Oncology, Department of Medicine III, University Hospital RWTH, Aachen 52074, Germany. Department of Medicine, Columbia University, New York, NY 10032, USA. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Munster 48149, Germany. Institute for Experimental Hematology, Hannover Medical School, Hannover 30625, Germany. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany; Translational Hepatology and Stem Cell Biology, Cluster of Excellence REBIRTH, Hannover Medical School, Hannover 30625, Germany. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany; Twincore Centre for Experimental and Clinical Infection Research, Hannover 30625, Germany. Electronic address: ott.michael@mh-hannover.de. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover 30625, Germany; Junior Research Group MicroRNA in Liver Regeneration, Cluster of Excellence REBIRTH, Hannover Medical School, Hannover 30625, Germany. Electronic address: sharma.amar@mh-hannover.de.
Identifiers:ISSN:1875-9777 (Electronic) %R 10.1016/j.stem.2016.01.0... [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/26923201 [ID No:2]
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