Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation
- Authors
- Lim, Hee Jung; Kim, Jusong; Park, Chang-Hwan; Lee, Sang A.; Lee, Man Ryul; Kim, Kye-Seong; Kim, Jaesang; Bae, Yun Soo
- Issue Date
- 8-Jan-2016
- Publisher
- American Society for Biochemistry and Molecular Biology Inc.
- Keywords
- c-Myc; Ahnak; InducedPluripotent Stem Cell
- Citation
- Journal of Biological Chemistry, v.291, no.2, pp 752 - 761
- Pages
- 10
- Journal Title
- Journal of Biological Chemistry
- Volume
- 291
- Number
- 2
- Start Page
- 752
- End Page
- 761
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/9418
- DOI
- 10.1074/jbc.M115.659276
- ISSN
- 0021-9258
1083-351X
- Abstract
- We have previously reported that Ahnak-mediated TGF beta signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with the c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak(-/-) MEF) show an increased level of c-Myc expression compared with wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2, and Klf4 (hereafter 3F), was significantly enhanced in Ahnak(-/-) MEF. Similar results were obtained when Ahnak-specific shRNA was applied to wild type MEF. Of note, expression of Ahnak was significantly induced during the formation of embryoid bodies from embryonic stem cells, suggesting that Ahnak-mediated c-Myc inhibition is involved in embryoid body formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak(-/-) MEF cells (Ahnak(-/-) - iPSC-3F) showed expression of all stem cell markers examined and the capability to form three primary germ layers. Moreover, injection of Ahnak(-/-) - iPSC-3F into athymic nude mice led to development of teratoma containing tissues from all three primary germ layers, indicating that iPSC from Ahnak(-/-) MEF are bona fide pluripotent stem cells. Taken together, these data provide evidence for a new role for Ahnak in cell fate determination during development and suggest that manipulation of Ahnak and the associated signaling pathway may provide a means to regulate iPSC generation.
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Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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