title: Inhibition of PTEN tumor suppressor promotes the generation of induced pluripotent stem cells.
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.
authors.affiliation: Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Liao
authors.forename: Tomotoshi
authors.initials: T
authors.lastname: Marumoto
authors.forename: Saori
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.forename: Naoki
authors.initials: N
authors.lastname: Takeda
authors.forename: Chika
authors.initials: C
authors.lastname: Sakamoto
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kawano
authors.forename: Takenobu
authors.initials: T
authors.lastname: Nii
authors.forename: Shohei
authors.initials: S
authors.lastname: Miyamato
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nagai
authors.forename: Michiyo
authors.initials: M
authors.lastname: Okada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inoue
authors.forename: Kohichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Miura
authors.forename: Kenzaburo
authors.initials: K
authors.lastname: Tani
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D007621:Karyotyping; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014638:Vanadates / Q000494:pharmacology
chemical_list: D014638:Vanadates; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse