RRC ID 12251
Author Araki R, Hoki Y, Uda M, Nakamura M, Jincho Y, Tamura C, Sunayama M, Ando S, Sugiura M, Yoshida MA, Kasama Y, Abe M.
Title Crucial role of c-Myc in the generation of induced pluripotent stem cells.
Journal 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.
Volume 29(9)
Pages 1362-70
Published 2011-9
DOI 10.1002/stem.685
PMID 21732496
MeSH Animals Blastomeres / physiology Chimera Embryonic Stem Cells / cytology Embryonic Stem Cells / physiology Female Genes, myc Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / metabolism Induced Pluripotent Stem Cells / physiology* Male Mice Mice, Inbred C57BL Pregnancy Proto-Oncogene Proteins c-myc / biosynthesis Proto-Oncogene Proteins c-myc / genetics* Transduction, Genetic
IF 5.614
Times Cited 27
Mice STOCK Tg(Nanog-GFP Puro)1Yam