Crucial Role of C‐Myc in the Generation of Induced Pluripotent Stem Cells

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 effe...

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Published inStem cells (Dayton, Ohio) Vol. 29; no. 9; pp. 1362 - 1370
Main Authors Araki, Ryoko, Hoki, Yuko, Uda, Masahiro, Nakamura, Miki, Jincho, Yuko, Tamura, Chihiro, Sunayama, Misato, Ando, Shunsuke, Sugiura, Mayumi, Yoshida, Mitsuaki A, Kasama, Yasuji, Abe, Masumi
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2011
Subjects
Animals
Blastomeres - physiology
Chimera
c‐Myc
Embryonic Stem Cells - cytology
Embryonic Stem Cells - physiology
Female
Genes, myc
Induced pluripotent stem cells
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
Online AccessGet full text
ISSN1066-5099
1549-4918
1549-4918
DOI10.1002/stem.685

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Summary: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. STEM CELLS 2011; 29:1362–1370
Bibliography:First published online in S
Disclosure of potential conflicts of interest is found at the end of this article.
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Author contributions: R.A.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, financial support; Y.H.: collection and assembly of data, and data analysis; M.U., M.N., C.T., M. Sunayama, S.A., M. Sugiura, and M.A.Y.: collection and assembly of data; Y.J.: collection and assembly of data, data analysis and interpretation; Y.K.: data analysis; M.A.: conception and design, financial support, manuscript writing, final approval of manuscript.
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July 5, 2011.
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ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1002/stem.685