| 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 |
2011-9-1
|
| 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 |
6.022
|
| Times Cited |
38
|
|
WOS Category
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
ONCOLOGY
HEMATOLOGY
CELL & TISSUE ENGINEERING
CELL BIOLOGY
|
| Resource |
| Mice |
RBRC02290 |
