title: Crucial role of c-Myc in the generation of induced pluripotent stem cells.
abstract: c-Myc transduction has been considered previously to be nonessential for induced pluripotent stem cell (iPSC) generation. In this study, we investigated the effects of c-Myc transduction on the generation of iPSCs from an inbred mouse strain using a genome integration-free vector to exclude the effects of the genetic background and the genomic integration of exogenous genes. Our findings reveal a clear difference between iPSCs generated using the four defined factors including c-Myc (4F-iPSCs) and those produced without c-Myc (3F-iPSCs). Molecular and cellular analyses did not reveal any differences between 3F-iPSCs and 4F-iPSCs, as reported previously. However, a chimeric mice formation test indicated clear differences, whereby few highly chimeric mice and no germline transmission was observed using 3F-iPSCs. Similar differences were also observed in the mouse line that has been widely used in iPSC studies. Furthermore, the defect in 3F-iPSCs was considerably improved by trichostatin A, a histone deacetyl transferase inhibitor, indicating that c-Myc plays a crucial role in iPSC generation through the control of histone acetylation. Indeed, low levels of histone acetylation were observed in 3F-iPSCs. Our results shed new light on iPSC generation mechanisms and strongly recommend c-Myc transduction for preparing high-quality iPSCs.
authors: Transcriptome Research Group, National Institute of Radiological Sciences, Chiba, Japan.
authors: Ryoko
authors: R
authors: Araki
authors: Yuko
authors: Y
authors: Hoki
authors: Masahiro
authors: M
authors: Uda
authors: Miki
authors: M
authors: Nakamura
authors: Yuko
authors: Y
authors: Jincho
authors: Chihiro
authors: C
authors: Tamura
authors: Misato
authors: M
authors: Sunayama
authors: Shunsuke
authors: S
authors: Ando
authors: Mayumi
authors: M
authors: Sugiura
authors: Mitsuaki A
authors: MA
authors: Yoshida
authors: Yasuji
authors: Y
authors: Kasama
authors: Masumi
authors: M
authors: Abe
mesh_terms: D000818:Animals; D001757:Blastomeres / Q000502:physiology; D002678:Chimera; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D005260:Female; D016259:Genes, myc; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D014161:Transduction, Genetic
chemical_list: C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc