Nuclear receptor gene alteration in human induced pluripotent stem cells with hepatic differentiation propensity
Noriko Itaba
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
These authors equally contributed to this work.Search for more papers by this authorPeninah M. Wairagu
Department of Biochemistry, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Korea
These authors equally contributed to this work.Search for more papers by this authorNatsumi Aramaki
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
These authors equally contributed to this work.Search for more papers by this authorToshihiro Yasui
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
These authors equally contributed to this work.Search for more papers by this authorYoshiaki Matsumi
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
Search for more papers by this authorYohei Kono
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
Search for more papers by this authorAi N.H. Phan
Department of Biochemistry, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Korea
Search for more papers by this authorMakoto Otsu
Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorTakahiro Kunisada
Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorYukio Nakamura
Cell Engineering Division, RIKEN BioResource Center, Ibaraki, Japan
Search for more papers by this authorHideyuki Okano
Department of Physiology, School of Medicine, Keio University, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Yangsik Jeong
Department of Biochemistry, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Korea
Correspondence: Dr Goshi Shiota, Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 36-1 Nishi-machi, Yonago 683-8504, Japan. Email: [email protected]; Dr Yangsik Jeong, Department of Biochemistry, Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, 20 Ilsan-ro, Wonju, Gangwon-do 220-701, Korea. Email: [email protected]Search for more papers by this authorCorresponding Author
Goshi Shiota
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
Correspondence: Dr Goshi Shiota, Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 36-1 Nishi-machi, Yonago 683-8504, Japan. Email: [email protected]; Dr Yangsik Jeong, Department of Biochemistry, Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, 20 Ilsan-ro, Wonju, Gangwon-do 220-701, Korea. Email: [email protected]Search for more papers by this authorNoriko Itaba
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
These authors equally contributed to this work.Search for more papers by this authorPeninah M. Wairagu
Department of Biochemistry, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Korea
These authors equally contributed to this work.Search for more papers by this authorNatsumi Aramaki
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
These authors equally contributed to this work.Search for more papers by this authorToshihiro Yasui
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
These authors equally contributed to this work.Search for more papers by this authorYoshiaki Matsumi
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
Search for more papers by this authorYohei Kono
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
Search for more papers by this authorAi N.H. Phan
Department of Biochemistry, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Korea
Search for more papers by this authorMakoto Otsu
Stem Cell Bank, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Search for more papers by this authorTakahiro Kunisada
Department of Tissue and Organ Development, Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, Gifu, Japan
Search for more papers by this authorYukio Nakamura
Cell Engineering Division, RIKEN BioResource Center, Ibaraki, Japan
Search for more papers by this authorHideyuki Okano
Department of Physiology, School of Medicine, Keio University, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Yangsik Jeong
Department of Biochemistry, Institute of Lifestyle Medicine and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, Wonju, Korea
Correspondence: Dr Goshi Shiota, Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 36-1 Nishi-machi, Yonago 683-8504, Japan. Email: [email protected]; Dr Yangsik Jeong, Department of Biochemistry, Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, 20 Ilsan-ro, Wonju, Gangwon-do 220-701, Korea. Email: [email protected]Search for more papers by this authorCorresponding Author
Goshi Shiota
Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, Yonago, Japan
Correspondence: Dr Goshi Shiota, Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 36-1 Nishi-machi, Yonago 683-8504, Japan. Email: [email protected]; Dr Yangsik Jeong, Department of Biochemistry, Institute of Lifestyle Medicine, and Nuclear Receptor Research Consortium, Wonju College of Medicine, Yonsei University, 20 Ilsan-ro, Wonju, Gangwon-do 220-701, Korea. Email: [email protected]Search for more papers by this authorAbstract
Aim
Human induced pluripotent stem (hiPS) cells are an alternative cell source of regenerative medicine for liver disease. Because variations in hepatic differentiation efficacy among hiPS cells exist, it is important to select a hiPS cell line with hepatic differentiation propensity. In addition, nuclear receptors (NR) regulate essential biological processes including differentiation and development. In this study, we identified the hiPS cell line with hepatic differentiation propensity and examined expression levels of 48 NR during this process.
Methods
We screened 28 hiPS cell lines, which are established from various tissues of healthy persons with various reprogramming methods, using a three-step differentiation method, and examined expression levels of 48 NR by quantitative real-time polymerase chain reaction during the differentiation process in the selected cells.
Results
hiPS-RIKEN-2B and hiPS-RIKEN-2F cells have hepatic differentiation propensity. Differentiation propensity towards endoderm was affected by donor origin but not by reprogramming methods or cell type of origins. Expression levels of NR were closely associated with those of hepatic differentiation markers. Furthermore, expression patterns of NR were categorized as five patterns. In particular, seven NR such as chicken ovalbumin upstream promoter transcription factor 1, retinoic acid receptor α, peroxisome proliferator-activated receptor-γ, progesterone receptor, photoreceptor cell-specific nuclear receptor, tailless homolog orphan receptor and glucocorticoid receptor were identified as the genes of which expression gradually goes up with differentiation.
Conclusion
These findings will be useful for not only elucidating mechanisms of hepatic differentiation of hiPS cells but also cell-based therapy for liver diseases.
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