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Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation
- Title
- 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
- Ewha Authors
- 배윤수; 김재상
- SCOPUS Author ID
- 배윤수; 김재상
- Issue Date
- 2016
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- ISSN
- 1083-351X
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY vol. 291, no. 2, pp. 752 - 761
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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.
- DOI
- 10.1074/jbc.M115.659276
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
- Files in This Item:
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