Regulation of c-Myc expression by Ahnak promotes induced pluripotent stem cell generation

Hee Jung Lim, Jusong Kim, Chang Hwan Park, Sang A. Lee, Man Ryul Lee, Kye Seong Kim, Jaesang Kim, Yun Soo Bae

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11 Scopus citations


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.

Original languageEnglish
Pages (from-to)752-761
Number of pages10
JournalJournal of Biological Chemistry
Issue number2
StatePublished - 8 Jan 2016

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© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.


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