Inhibition of PTEN Tumor Suppressor Promotes the Generation of Induced Pluripotent Stem Cells |
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Authors: | Jiyuan Liao Tomotoshi Marumoto Saori Yamaguchi Shinji Okano Naoki Takeda Chika Sakamoto Hirotaka Kawano Takenobu Nii Shohei Miyamoto Yoko Nagai Michiyo Okada Hiroyuki Inoue Kohichi Kawahara Akira Suzuki Yoshie Miura Kenzaburo Tani |
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Affiliation: | 1. Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan;2. Department of Advanced Molecular and Cell Therapy, Kyushu University Hospital, Fukuoka, Japan;3. Division of Pathophysiological and Experimental Pathology, Department of Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;4. Division of Transgenic Technology, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan;5. Division of Cancer Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan |
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Abstract: | Induced pluripotent stem cells (iPSCs) can be generated from patients with specific diseases by the transduction of reprogramming factors and can be useful as a cell source for cell transplantation therapy for various diseases with impaired organs. However, the low efficiency of iPSC derived from somatic cells (0.01–0.1%) is one of the major problems in the field. The phosphoinositide 3-kinase (PI3K) pathway is thought to be important for self-renewal, proliferation, and maintenance of embryonic stem cells (ESCs), but the contribution of this pathway or its well-known negative regulator, phosphatase, and tensin homolog deleted on chromosome ten (Pten), to somatic cell reprogramming remains largely unknown. Here, we show that activation of the PI3K pathway by the Pten inhibitor, dipotassium bisperoxo(5-hydroxypyridine-2-carboxyl)oxovanadate, improves the efficiency of germline-competent iPSC derivation from mouse somatic cells. This simple method provides a new approach for efficient generation of iPSCs. |
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