Crucial role of c-Myc in the generation of induced pluripotent stem cells.
Stem Cells
; 29(9): 1362-70, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21732496
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.
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1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas c-myc
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Células Madre Pluripotentes Inducidas
Límite:
Animals
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Pregnancy
Idioma:
En
Año:
2011
Tipo del documento:
Article