Inhibition of PTEN Tumor Suppressor Promotes the Generation of Induced Pluripotent Stem Cells

• Published in: Molecular therapy Vol. 21; no. 6; pp. 1242 - 1250
• Main Authors: Liao, Jiyuan, Marumoto, Tomotoshi, Yamaguchi, Saori, Okano, Shinji, Takeda, Naoki, Sakamoto, Chika, Kawano, Hirotaka, Nii, Takenobu, Miyamoto, Shohei, Nagai, Yoko, Okada, Michiyo, Inoue, Hiroyuki, Kawahara, Kohichi, Suzuki, Akira, Miura, Yoshie, Tani, Kenzaburo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2013; Elsevier Limited; Nature Publishing Group
• Subjects: Animals; Cell Proliferation; Cells, Cultured; Efficiency; Embryonic Stem Cells - cytology; Embryonic Stem Cells - metabolism; Female; Genetic Vectors; Immunohistochemistry; Induced Pluripotent Stem Cells - cytology; Karyotyping; Kinases; Male; Mice; Mice, Inbred ICR; Original; Phosphatase; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Promoter Regions, Genetic; PTEN Phosphohydrolase - antagonists & inhibitors; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Retroviridae - genetics; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - drug effects; Stem cells; Vanadates - pharmacology; Japan
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2013.60

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.