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



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ID: 732126.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
Small Molecules Facilitate Single Factor-Mediated Hepatic Reprogramming
Authors:Lim, K. T.; Lee, S. C.; Gao, Y.; Kim, K. P.; Song, G.; An, S. Y.; Adachi, K.; Jang, Y. J.; Kim, J.; Oh, K. J.; Kwak, T. H.; Hwang, S. I.; You, J. S.; Ko, K.; Koo, S. H.; Sharma, A. D.; Kim, J. H.; Hui, L.; Cantz, T.; Scholer, H. R.; Han, D. W.
Date of Publication (YYYY-MM-DD):2016-04-13
Title of Journal:Cell Rep
Review Status:Internal review
Audience:Not Specified
Abstract / Description:Recent studies have shown that defined factors could lead to the direct conversion of fibroblasts into induced hepatocyte-like cells (iHeps). However, reported conversion efficiencies are very low, and the underlying mechanism of the direct hepatic reprogramming is largely unknown. Here, we report that direct conversion into iHeps is a stepwise transition involving the erasure of somatic memory, mesenchymal-to-epithelial transition, and induction of hepatic cell fate in a sequential manner. Through screening for additional factors that could potentially enhance the conversion kinetics, we have found that c-Myc and Klf4 (CK) dramatically accelerate conversion kinetics, resulting in remarkably improved iHep generation. Furthermore, we identified small molecules that could lead to the robust generation of iHeps without CK. Finally, we show that Hnf1alpha supported by small molecules is sufficient to efficiently induce direct hepatic reprogramming. This approach might help to fully elucidate the direct conversion process and also facilitate the translation of iHep into the clinic.
Free Keywords:Met; conversion kinetics; direct conversion; induced hepatocytes
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea; Department of Advanced Translational Medicine, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Rontgenstrasse 20, 48149 Munster, Germany. Department of Gastroenterology, Hepatology, and Endocrinology, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover 30625, Germany. Laboratory of Stem Cell Biology, Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea. Department of Biochemistry, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea. Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Rontgenstrasse 20, 48149 Munster, Germany; Department of Gastroenterology, Hepatology, and Endocrinology, REBIRTH Cluster of Excellence, Hannover Medical School, Hannover 30625, Germany. Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea; Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Rontgenstrasse 20, 48149 Munster, Germany; Medical Faculty, University of Munster, Domagkstrasse 3, 48149 Munster, Germany. Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul 143-701, Republic of Korea; KU Open-Innovation Center, Institute of Biomedical Science & Technology, Konkuk University, Seoul 143-701, Republic of Korea; Department of Advanced Translational Medicine, School of Medicine, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: dwhan@konkuk.ac.kr.
Identifiers:ISSN:2211-1247 (Electronic) %R 10.1016/j.celrep.2016.03... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/27149847 [ID No:2]
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