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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 H.J.Kim J.Park C.-H.Lee S.A.Lee M.R.Kim K.-S.Bae Y.S.
Ewha Authors
배윤수김재상
SCOPUS Author ID
배윤수scopus; 김재상scopus
Issue Date
2016
Journal Title
Journal of Biological Chemistry
ISSN
0021-9258JCR Link
Citation
vol. 291, no. 2, pp. 752 - 761
Publisher
American Society for Biochemistry and Molecular Biology Inc.
Indexed
SCI; SCIE; SCOPUS scopus
Abstract
Wehave previously reported that Ahnak-mediated TGFβ 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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
DOI
10.1074/jbc.M115.659276
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자연과학대학 > 생명과학전공 > Journal papers
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